Epidemiology, clinical features, and classification of 3,404 patients with uveitis: Colombian Uveitis Multicenter Study (COL-UVEA).

PURPOSE: To describe the epidemiology, clinical features, and classification of uveitis in a large cohort of Colombian patients. METHODS: Data were collected from seven ophthalmological referral centers in the four main cities in Colombia. The study included patients with a confirmed diagnosis of uveitis from January 2010 to December 2022. Information on demographics, ophthalmic examination findings, uveitis classification, and etiology was recorded. RESULTS: The study reviewed 3,404 clinical records of patients with uveitis. The mean age at diagnosis was 41.1 (SD 19.0) years, and 54.2% of the patients were female. Overall, 1,341(39.4%) were infectious, 626 (18.4%) non-infectious, and four masquerade syndromes (0.1%). The most common types of uveitis were unilateral (66.7%), acute (48.3%), and non-granulomatous (83%). Anterior uveitis was the most common anatomical localization (49.5%), followed by posterior uveitis (22.9%), panuveitis (22.3%), and intermediate uveitis (5.2%). A diagnosis was established in 3,252 (95.5%) cases; idiopathic was the most common cause (27.7%), followed by toxoplasmosis (25.3%) and virus-associated uveitis (6.4%). The age group between 30 and 50 exhibited the highest frequency of uveitis. CONCLUSION: This multicenter study comprehensively describes uveitis characteristics in Colombian patients, providing valuable insights into its demographic and clinical features. The study findings emphasize the need to continue updating the changing patterns of uveitis to improve diagnosis and treatment strategies for diseases associated with intraocular inflammation.

Hepatitis E and diaphragmatic dysfunction: Case series and review of the literature.

INTRODUCTION: The causes of diaphragmatic paresis are manifold. An association between neuralgic amyotrophy (NA) and hepatitis E virus (HEV) infection has been reported. We wondered about the prevalence of diaphragmatic disfunction and hepatitis E infection in our clinic. METHODS: From July 1st, 2020 to August 31st, 2023, patients presenting with diaphragmatic dysfunction and simultaneous clinical symptoms of an acute NA, or a history of NA, as well as patients with previously unexplained diaphragmatic dysfunction were examined for HEV infection. RESULTS: By August 31st, 2023, 13 patients with diaphragmatic dysfunction and HEV infection were diagnosed (4 women, 9 men). Mean age was 59 ± 10 years. Liver values were normal in all patients. The median latency to diagnosis was five months (range: 1-48 months); nine patients, 4 of them with typical symptoms of NA, presented with acute onset three patients showed bilateral diaphragmatic dysfunction. All patients had a positive IgG immunoblot. Seven patients, three with NA, had an elevated hepatitis E IgM titer and six of them also a positive IgM immunoblot. In all cases, O2C hepatitis genotype 3 was identified. In eight cases, all those with a high IgG titer >125, the O2 genotype 1 was also detected. CONCLUSION: NA that shows involvement of the phrenic nerve resulting in diaphragmatic dysfunction and dyspnoea, may be associated with HEV infection. The observation of 13 patients with diaphragmatic dysfunctions and HEV infection within a period of three years indicates a high number of undetected HEV-associated diaphragmatic dysfunction in the population, especially in the absence of NA symptoms. Therefore, even in diaphragmatic dysfunction without NA symptoms and causative damaging event, HEV infection should be considered, as it may represent a subform of NA with only phrenic nerve involvement. Therapy of HEV-associated diaphragmatic dysfunction in the acute phase is an open question. In view of the poor prognosis for recovery, antiviral therapy should be discussed. However, no relevant data are currently available.

Outcomes of accelerated corneal cross-linking for pediatric and adult keratoconus: a comparative study.

PURPOSE: To compare the visual, refractive, and topographic outcomes of a high irradiance accelerated corneal crosslinking (ACXL) protocol after a 12-month follow-up between pediatric and adult patients with progressive keratoconus (KC). METHODS: Retrospective, comparative, cohort study. Patients with KC were divided into two groups: pediatric (≤ 18 years) and adult (> 18 years). All of them were managed with epi-OFF ACXL (30 mW/cm2, 8 min, pulsed 1:1 on and off = 7.2 J/cm2). Visual, refractive, and topographic values were measured preoperatively and at 1, 3, 6, and 12 months postoperative. KC progression, defined as a Kmax increase of ≥ 1D during follow-up, was recorded. RESULTS: Eighty-nine eyes (53 patients) were included for analysis; 45 (50.6%) eyes were from pediatric patients and 44 (49.4%) from adults. At one-year follow-up, pediatric patients experienced significantly higher rates of progression (22.2% vs. 4.5%, p = .014). Contrariwise, female gender (Beta = - 3.62, p = .018), a baseline uncorrected visual acuity of Snellen ≥ 20/60 (Beta = - 5.96, p = .007), and being ≥ 15 years at ACXL treatment (Beta = - 0.31, p = .021) were associated with non-progressive disease. A significant improvement in best-corrected visual acuity, Kmin, Km, and Kmax was recorded in both groups. Overall, 86.5% of eyes from both groups showed Kmax stabilization or improvement. CONCLUSIONS: Despite the similarity in visual, refractive, and topographic outcomes in both groups, younger age was associated with KC progression after ACXL at one year of follow-up.

Anti-GM-CSF Neutralizing Autoantibodies in Colombian Patients with Disseminated Cryptococcosis.

BACKGROUND: Cryptococcosis is a potentially life-threatening fungal disease caused by encapsulated yeasts of the genus Cryptococcus, mostly C. neoformans or C. gattii. Cryptococcal meningitis is the most frequent clinical manifestation in humans. Neutralizing autoantibodies (auto-Abs) against granulocyte-macrophage colony-stimulating factor (GM-CSF) have recently been discovered in otherwise healthy adult patients with cryptococcal meningitis, mostly caused by C. gattii. We hypothesized that three Colombian patients with cryptococcal meningitis caused by C. neoformans in two of them would carry high plasma levels of neutralizing auto-Abs against GM-CSF. METHODS: We reviewed medical and laboratory records, performed immunological evaluations, and tested for anti-cytokine auto-Abs three previously healthy HIV-negative adults with disseminated cryptococcosis. RESULTS: Peripheral blood leukocyte subset levels and serum immunoglobulin concentrations were within the normal ranges. We detected high levels of neutralizing auto-Abs against GM-CSF in the plasma of all three patients. CONCLUSIONS: We report three Colombian patients with disseminated cryptococcosis associated with neutralizing auto-Abs against GM-CSF. Further studies should evaluate the genetic contribution to anti-GM-CSF autoantibody production and the role of the GM-CSF signaling pathway in the immune response to Cryptococcus spp.

Germline CYBB mutations that selectively affect macrophages in kindreds with X-linked predisposition to tuberculous mycobacterial disease.

Germline mutations in CYBB, the human gene encoding the gp91(phox) subunit of the phagocyte NADPH oxidase, impair the respiratory burst of all types of phagocytes and result in X-linked chronic granulomatous disease (CGD). We report here two kindreds in which otherwise healthy male adults developed X-linked recessive Mendelian susceptibility to mycobacterial disease (MSMD) syndromes. These patients had previously unknown mutations in CYBB that resulted in an impaired respiratory burst in monocyte-derived macrophages but not in monocytes or granulocytes. The macrophage-specific functional consequences of the germline mutation resulted from cell-specific impairment in the assembly of the NADPH oxidase. This 'experiment of nature' indicates that CYBB is associated with MSMD and demonstrates that the respiratory burst in human macrophages is a crucial mechanism for protective immunity to tuberculous mycobacteria.

Identification of potential invasive alien species in Spain through horizon scanning.

Invasive alien species have widespread impacts on native biodiversity and ecosystem services. Since the number of introductions worldwide is continuously rising, it is essential to prevent the entry, establishment and spread of new alien species through a systematic examination of future potential threats. Applying a three-step horizon scanning consensus method, we evaluated non-established alien species that could potentially arrive, establish and cause major ecological impact in Spain within the next 10 years. Overall, we identified 47 species with a very high risk (e.g. Oreochromis niloticus, Popillia japonica, Hemidactylus frenatus, Crassula helmsii or Halophila stipulacea), 61 with high risk, 93 with moderate risk, and 732 species with low risk. Many of the species categorized as very high or high risk to Spanish biodiversity are either already present in Europe and neighbouring countries or have a long invasive history elsewhere. This study provides an updated list of potential invasive alien species useful for prioritizing efforts and resources against their introduction. Compared to previous horizon scanning exercises in Spain, the current study screens potential invaders from a wider range of terrestrial, freshwater, and marine organisms, and can serve as a basis for more comprehensive risk analyses to improve management and increase the efficiency of the early warning and rapid response framework for invasive alien species. We also stress the usefulness of measuring agreement and consistency as two different properties of the reliability of expert scores, in order to more easily elaborate consensus ranked lists of potential invasive alien species.

Atmospheric PAHs in rural, urban, industrial and beach locations in Buenos Aires Province, Argentina: sources and health risk assessment.

The first atmospheric PAHs levels and associated inhalation cancer risk were assessed over southwest Buenos Aires region by deploying PUF disk PAS samplers. Eight sampling location included coastal zones, touristic beaches, and rural inland areas were considered. PUF disks were fortified with surrogate standards and extracted by automated Soxhlet prior to GC-MS analysis. Σ16 PAHs ranged from 1.13 to 44.5 ng m-3 (10.3 ± 9.8), while urban locations showed up to 10 times higher PAH levels than rural or beach locations. Direct sources of PAHs, such as intensive vehicle traffic, heating, and general combustion activities, were identified. PAHs with four to six rings (46.62%) were predominantly Flt, Pyr, BbF, and BkF, and carcinogenic risk was expressed by BaP (0.10 ± 0.07 ng m-3) and BaPTEQs (0.26 ± 0.22 ng m-3). Inhalation ECR (2.23E-5, WHO) presented the lowest risk at beach locations. Molecular ratios and PCA showed a strong dominance in pyrolytic sources, such as biomass and coal combustion, with a particular signature in fires at inland locations. Overall, this study demonstrated that PUF disk passive air sampling provided a sound and simple approach for tracking air PAHs, their sources and public health risks, bringing a cost-effective tool for pollution control measures, even at small and remote towns. This is particularly relevant in extensive countries with medium or low income, such as Argentina.

Inherited GATA2 Deficiency Is Dominant by Haploinsufficiency and Displays Incomplete Clinical Penetrance.

PURPOSE: Germline heterozygous mutations of GATA2 underlie a variety of hematological and clinical phenotypes. The genetic, immunological, and clinical features of GATA2-deficient patients with mycobacterial diseases in the familial context remain largely unknown. METHODS: We enrolled 15 GATA2 index cases referred for mycobacterial disease. We describe their genetic and clinical features including their relatives. RESULTS: We identified 12 heterozygous GATA2 mutations, two of which had not been reported. Eight of these mutations were loss-of-function, and four were hypomorphic. None was dominant-negative in vitro, and the GATA2 locus was found to be subject to purifying selection, strongly suggesting a mechanism of haploinsufficiency. Three relatives of index cases had mycobacterial disease and were also heterozygous, resulting in 18 patients in total. Mycobacterial infection was the first clinical manifestation in 11 patients, at a mean age of 22.5 years (range: 12 to 42 years). Most patients also suffered from other infections, monocytopenia, or myelodysplasia. Strikingly, the clinical penetrance was incomplete (32.9% by age 40 years), as 16 heterozygous relatives aged between 6 and 78 years, including 4 older than 60 years, were completely asymptomatic. CONCLUSION: Clinical penetrance for mycobacterial disease was found to be similar to other GATA2 deficiency-related manifestations. These observations suggest that other mechanisms contribute to the phenotypic expression of GATA2 deficiency. A diagnosis of autosomal dominant GATA2 deficiency should be considered in patients with mycobacterial infections and/or other GATA2 deficiency-related phenotypes at any age in life. Moreover, all direct relatives should be genotyped at the GATA2 locus.

Short-term exposure to benzalkonium chloride in bacteria from activated sludge alters the community diversity and the antibiotic resistance profile.

The continuous introduction of cleaning products containing benzalkonium chloride (BAC) from household discharges can mold the microbial communities in wastewater treatment plants (WWTPs) in a way still poorly understood. In this study, we performed an in vitro exposure of activated sludge from a WWTP in Costa Rica to BAC, quantified the changes in intI1, sul2, and qacE/qacEΔ1 gene profiles, and determined alterations in the bacterial community composition. The analysis of the qPCR data revealed elevated charges of antibiotic resistance genes in the microbial community; after BAC's exposure, a significant increase in the qacE/qacEΔ1 gene, which is related to ammonium quaternary resistance, was observed. The 16S rRNA gene sequences' analysis showed pronounced variations in the structure of the bacterial communities, including reduction of the alpha diversity values and an increase of the relative abundance of Alphaproteobacteria, particularly of Rhodospseudomonas and Rhodobacter. We confirmed that the microbial communities presented high resilience to BAC at the mg/mL concentration, probably due to constant exposure to this pollutant. They also presented antibiotic resistance-related genes with similar mechanisms to tolerate this substance. These mechanisms should be explored more thoroughly, especially in the context of high use of disinfectant.

Tinea faciei caused by Trichophyton benhamiae in a child.

Tinea faciei is a common pediatric skin disease, most often caused by fungi of the genus Trichophyton. T benhamiae has been recently reclassified as a distinct species and is recognized as an emerging zoonotic dermatophyte with a wide range of possible infectious reservoirs worldwide. We present a previously healthy 7-year-old child presenting with unusual inflammatory facial plaques due to T benhamiae, confirmed by mass spectroscopy.

Distribution of Butyltin Compounds in the Coastal Environment of the Bahía Blanca Estuary, Argentina.

This study evaluates for the first time the distribution and accumulation of butyltin compounds (BTs) in different compartments such as seawater, sediments, suspended particulate matter (SPM), and mussels (Brachidontes rodriguezii) in the Bahía Blanca estuary. The samples were collected from six sampling sites with different anthropogenic impacts. A better visualization and interpretation of data was achieved using chemometric tools (Tucker4 model), which made it possible to reveal the main relationships among the variables. This analysis showed the presence of BTs in all the estuarine environmental compartments, even in sites with low human intervention. The relationships found among BTs levels, seasons, and environmental matrices show the importance of biological processes such as phytoplankton blooms and remobilization of sediments (by tidal dynamics and/or periodic dredging) in BTs distribution and degradation. In addition, partition coefficients showed that mussels mainly bioaccumulate tributyltin from sediment, water and, to a lesser extent, SPM.

Endoscopic retrograde cholangiopancreatography results three days after a failed pre-cut.

INTRODUCTION: deep cannulation of the common bile duct is essential in endoscopic retrograde cholangiopancreatography (ERCP). However, cannulation is not possible in approximately 20 % of the cases with the usual techniques. Pre-cutting is an alternative that allows cannulation in difficult cases although its success is not guaranteed. Repeating the ERCP within three days of a failed pre-cut is an acceptable option. OBJECTIVE: to determine if an ERCP performed three days after a failed pre-cut papillotomy allows the bile duct to be cannulated without increasing complication rates. PATIENTS AND METHODS: patients who underwent an ERCP plus pre-cut were included, in whom the common bile duct could not be cannulated and who also underwent a new ERCP three days after the initial pre-cut. The primary objective was a successful biliary cannulation in the second ERCP and the secondary objective were the complications of the initial pre-cut. RESULTS: forty patients with an average age of 65 years were identified and 57 % were male. The indications for ERCP were choledocholithiasis in 95 %, biliary fistula in 2.5 % and pancreatic neoplasia in 2.5 %. The ERCP was repeated three days later in 92.5 % of the cases and the biliary cannulation was successful in 78.3 %. CONCLUSIONS: a new ERCP performed within three days of a failed pre-cut is justifiable since it has a significant success rate. Bile duct cannulation is achieved in three out of four patients, with an acceptable percentage of complications.

Assessing threats, regulations, and strategies to abate plastic pollution in LAC beaches during COVID-19 pandemic.

Plastic use and production have dramatically increased globally over the past 65 years with the improvement of life quality by the daily use of plastic products. Still, around 50% of the plastic produced is disposable products that generate substantial waste. Several reports pointed out the adverse effects of plastic litter in coastal environments in recent years, emphasizing single-use plastics (SUP). In this manner, Latin America and the Caribbean (LAC) coastal environments are highly vulnerable due to wastewater treatment facilities scarcity and poor plastic waste management strategies. Since COVID-19 pandemic, the single-use plastic waste/person rate is expected to rise due to the use of personal protective equipment and SUP as health care measures. Based on literature research and the review of plastic waste regulations, this paper will assess the main COVID-19 plastic pollution threats and LAC beaches' regulations to suggest possible measures to abate this problem. The main findings suggest that unifying the ongoing fragmented and overlapped policies is key to abate plastic pollution, including plastic industry regulations and circular economies. In addition, increasing public risk perception about plastic pollution is critical to reducing plastic waste generation. Research advances in the adverse effects of plastic debris could improve the public's perception of plastic pollution risk, pushing forward global marine plastic governance.

T-cell defects in patients with ARPC1B germline mutations account for combined immunodeficiency.

ARPC1B is a key factor for the assembly and maintenance of the ARP2/3 complex that is involved in actin branching from an existing filament. Germline biallelic mutations in ARPC1B have been recently described in 6 patients with clinical features of combined immunodeficiency (CID), whose neutrophils and platelets but not T lymphocytes were studied. We hypothesized that ARPC1B deficiency may also lead to cytoskeleton and functional defects in T cells. We have identified biallelic mutations in ARPC1B in 6 unrelated patients with early onset disease characterized by severe infections, autoimmune manifestations, and thrombocytopenia. Immunological features included T-cell lymphopenia, low numbers of naïve T cells, and hyper-immunoglobulin E. Alteration in ARPC1B protein structure led to absent/low expression by flow cytometry and confocal microscopy. This molecular defect was associated with the inability of patient-derived T cells to extend an actin-rich lamellipodia upon T-cell receptor (TCR) stimulation and to assemble an immunological synapse. ARPC1B-deficient T cells additionally displayed impaired TCR-mediated proliferation and SDF1-α-directed migration. Gene transfer of ARPC1B in patients' T cells using a lentiviral vector restored both ARPC1B expression and T-cell proliferation in vitro. In 2 of the patients, in vivo somatic reversion restored ARPC1B expression in a fraction of lymphocytes and was associated with a skewed TCR repertoire. In 1 revertant patient, memory CD8+ T cells expressing normal levels of ARPC1B displayed improved T-cell migration. Inherited ARPC1B deficiency therefore alters T-cell cytoskeletal dynamics and functions, contributing to the clinical features of CID.

Isotretinoin and the eye: A review for the dermatologist.

Due to the prevalence of acne vulgaris, isotretinoin is one of the most prescribed drugs among physicians and dermatologists. Although exhibiting an adequate safety profile, adverse events secondary to isotretinoin use are common. Before prescribing isotretinoin, physicians usually inquire about pregnancy and perform serologic tests including cholesterol, triglycerides, and liver enzymes. Ocular manifestations are commonly neglected. Despite being generally mild, ocular manifestations related to either topical or systemic isotretinoin may cause important ocular morbidity. The ocular surface is the most affected site within the eye; however, retinal and optic nerve disease also have been documented. Evaporative dry eye disease, which may range from mild to severe, is the most common adverse ocular effect associated with isotretinoin use. The aim of this review is to present an up-to-date overview for the dermatologist about the prevention, diagnosis, and treatment of the ocular side effects of isotretinoin, and when to refer to the eye specialist.

Effect of the veterinary ionophore monensin on the structure and activity of a tropical soil bacterial community.

Monensin (MON) is a coccidiostat used as a growth promoter that can reach the environment through fertilization with manure from farm animals. To verify whether field-relevant concentrations of this drug negatively influence the structure and activity of tropical soil bacteria, plate counts, CO2 efflux measurements, phospholipid fatty acids (PLFA) and community-level physiological profiling (CLPP) profiles were obtained for soil microcosms exposed to 1 or 10 mg kg-1 of MON across 11 days. Although 53% (1 mg kg-1) to 40% (10 mg kg-1) of the MON concentrations added to the microcosms dissipated within 5 days, a subtle concentration-dependent decrease in the number of culturable bacteria (<1 log CFU g-1), reduced (-20 to -30%) or exacerbated (+25%) soil CO2 effluxes, a marked shift of non-bacterial fatty acids, and altered respiration of amines (1.22-fold decrease) and polymers (1.70-fold increase) were noted in some of the treatments. These results suggest that MON quickly killed some microorganisms and that the surviving populations were selected and metabolically stimulated. Consequently, MON should be monitored in agronomic and environmental systems as part of One Health efforts.

Microplastics integrating the zooplanktonic fraction in a saline lake of Argentina: influence of water management.

This study address for the first time in Argentina and the South American continent the effect of water management on the presence of microplastics (MPs) in a shallow lake, assessing their contribution to the zooplankton fraction. Water samples were collected in the lake and its principal affluent, an irrigation channel, from winter 2018 to summer 2019 with a zooplankton net (47 µm). MPs were present in all analyzed samples, with a dominance of fibers, black color, and ≤ 1000 µm range size. MPs concentration was maximum during summer at the lake (180 MPs m-3) while during spring (140 MPs m-3) at the channel. Rotifers and cyclopoids dominated the zooplanktonic fraction at both sites which range sizes (< 200 to 600 µm) included most of the size range found for MPs (50-950 µm). According to our results, the MPs found represents a potential risk for the first levels of the food web. In the lake, the concentration of MPs concerning total zooplankton abundance was higher when the channel was closed. Nevertheless, when the channel was open, the higher concentration in summer matches with the increase of tourism and an extraordinary rainfall. Our results suggest that while the runoff of agro-industrial waste regulates the MPs concentration in the channel, its water management, the touristic activities, and the runoff of MPs from nearby urban settlements regulate the concentration of MPs in the lake. These findings emphasize the need for better treatment of urban and agro-industrial waste that develops near continental aquatic systems, mainly in those where tourism activities are frequent and treatment facilities scarce.

Preliminary studies about the role of physicochemical parameters on the organotin compound dynamic in a South American estuary (Bahía Blanca, Argentina).

This work provides a preliminary study of the destination, mobility, and availability of tributyltin (TBT), dibutyltin (DBT), and monobutyltin (MBT) in contaminated sediments and water column within Puerto Rosales Port, located in the middle zone of the Bahía Blanca Estuary (Argentina). Therefore, this study presents the first comprehensive results of the role of several physicochemical parameters (temperature, pH, Eh, salinity, turbidity, organic matter, chlorophyll, and macronutrients) in behavior of organotin compounds (OTCs) in a marine-coastal ecosystem. The samples were collected seasonally in May, August, and November during 2014. Levels of OTCs were determined in sediments and water column samples by means of gas chromatography-mass spectrometry analysis. Degradation index analyses suggested not recent inputs of TBT at the area of study. However, results submitted a continuous input of TBT into the column water; further, its distribution and degradation pattern were shown to be influenced by salinity, turbidity, particulate organic matter, chlorophyll, and nitrates. These last two parameters, chlorophyll and nitrates, also were very important for sediment samples. Chlorophyll together with high temperatures recorded in the surface sediments triggers biodegradation process of TBT and DBT resulting in high MBT levels while nitrates seemed to promote debutylation process. Furthermore, pH appeared to influence drastically the adsorption/desorption activity of TBT and DBT in sediment. Finally, the Eh obtained suggested a degradation of TBT thanks to the presence of Fe (III) in this compartment. In addition, in fact, the results outlined a possible MBT additional input that contributes to the pollution observed in the study area. Graphical abstract Organotin compounds behavior according to several physicochemical parameters.

Evidence of Microplastic Ingestion by Fish from the Bahía Blanca Estuary in Argentina, South America.

The aim of this study was to assess - for the first time - the occurrence and distribution of microplastics (MPs) in the gastrointestinal tracts (GITs) of a marine commercial fish species (Micropogonias furnieri) from the Bahía Blanca Estuary (BBE) in Argentina, and to evaluate fish potential associated stress. In order to do this, juveniles were sampled using artisanal fishing arts at two sampling locations. Basic measurements of individual fish were taken (total length, total weight, weight of the liver) and GITs were subsequently removed, digested with 30% H2O2 for 5 days at 60°C, filtered on Whatman paper and then dried. Samples were observed with a stereomicroscope, and it was demonstrated that 100% of the individuals contained microplastic particles in their GITs. In total, 241 microplastic particles were removed from the GITs of all fish. They were categorized as fibers (60.8%), pellets (28.9%), fragments (8.6%) and laminas (1.4%), and they ranged in size from 0.98 to > 5 mm. The average number of particles per fish was higher than that reported in previous global marine studies. Moreover, a positive correlation between the number of MPs per fish and hepatosomatic index was found, suggesting a probable stress in their health condition. These findings provide the first and southernmost evidence of microplastic contamination in biota from the Argentinean sea, which is found in the South Atlantic sea.

Early-Onset Invasive Infection Due to Corynespora cassiicola Associated with Compound Heterozygous CARD9 Mutations in a Colombian Patient.

PURPOSE: CARD9 deficiency is an inborn error of immunity that predisposes otherwise healthy humans to mucocutaneous and invasive fungal infections, mostly caused by Candida, but also by dermatophytes, Aspergillus, and other fungi. Phaeohyphomycosis are an emerging group of fungal infections caused by dematiaceous fungi (phaeohyphomycetes) and are being increasingly identified in patients with CARD9 deficiency. The Corynespora genus belongs to phaeohyphomycetes and only one adult patient with CARD9 deficiency has been reported to suffer from invasive disease caused by C. cassiicola. We identified a Colombian child with an early-onset, deep, and destructive mucocutaneous infection due to C. cassiicola and we searched for mutations in CARD9. METHODS: We reviewed the medical records and immunological findings in the patient. Microbiologic tests and biopsies were performed. Whole-exome sequencing (WES) was made and Sanger sequencing was used to confirm the CARD9 mutations in the patient and her family. Finally, CARD9 protein expression was evaluated in peripheral blood mononuclear cells (PBMC) by western blotting. RESULTS: The patient was affected by a large, indurated, foul-smelling, and verrucous ulcerated lesion on the left side of the face with extensive necrosis and crusting, due to a C. cassiicola infectious disease. WES led to the identification of compound heterozygous mutations in the patient consisting of the previously reported p.Q289* nonsense (c.865C > T, exon 6) mutation, and a novel deletion (c.23_29del; p.Asp8Alafs10*) leading to a frameshift and a premature stop codon in exon 2. CARD9 protein expression was absent in peripheral blood mononuclear cells from the patient. CONCLUSION: We describe here compound heterozygous loss-of-expression mutations in CARD9 leading to severe deep and destructive mucocutaneous phaeohyphomycosis due to C. cassiicola in a Colombian child.