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In archaeological soil and sediment micromorphology, research is grounded in observations made with petrographic microscopes. These observations are recorded using standardised terms and microphotographs. The two-pillar database system allows a user-friendly recording of these observations with I-GEOARCHrec and the possibility to link these data to field pictures and microphotographs publicly available in I-GEOARCHive.

Of 27 patients with the acquired immunodeficiency syndrome (AIDS) in Tucson, Arizona, 7 had concurrent coccidioidomycosis. Early manifestations of infection in 6 patients included diffuse nodular pulmonary infiltrates and Coccidioides immitis in many extrathoracic sites. By comparison, a retrospective review of the cases of 300 patients hospitalized with coccidioidal infection identified only 13 patients without AIDS who had the same extent of infection, and only 3 of these patients had no immunosuppressing conditions. Antibodies for coccidioidal antigens at serum dilutions as high as 1:2048 were detected in 5 of the 7 patients with AIDS. Six had temporary responses to amphotericin B treatment, taken both alone and combined with ketoconazole, but all died within 14 months of their diagnosis of coccidioidomycosis. Because annual rates of coccidioidal infection in the Tucson area are 4% or less, the rate of 27% that we calculated, based on 7 patients having the infection during 26 years of risk for AIDS, suggests frequent reactivation of the infection or enhanced susceptibility to endemic exposure in persons with AIDS. [ABSTRACT FROM AUTHOR]

Scedosporium spp. and Lomentospora prolificans are emerging non-Aspergillus filamentous fungi. The Scedosporiosis/lomentosporiosis Observational Study we previously conducted reported frequent fungal vascular involvement, including aortitis and peripheral arteritis. For this article, we reviewed 7 cases of Scedosporium spp. and L. prolificans arteritis from the Scedosporiosis/lomentosporiosis Observational Study and 13 cases from published literature. Underlying immunosuppression was reported in 70% (14/20) of case-patients, mainly those who had solid organ transplants (10/14). Osteoarticular localization of infection was observed in 50% (10/20) of cases; infections were frequently (7/10) contiguous with vascular infection sites. Scedosporium spp./Lomentospora prolificans infections were diagnosed in 9 of 20 patients ≈3 months after completing treatment for nonvascular scedosporiosis/lomentosporiosis. Aneurysms were found in 8/11 aortitis and 6/10 peripheral arteritis cases. Invasive fungal disease--related deaths were high (12/18 [67%]). The vascular tropism of Scedosporium spp. and L. prolificans indicates vascular imaging, such as computed tomography angiography, is needed to manage infections, especially for osteoarticular locations.

Acute hepatic porphyrias are inherited metabolic disorders of heme biosynthesis characterized by the accumulation of toxic intermediate metabolites responsible for disabling acute neurovisceral attacks. Givosiran is a newly approved siRNA-based treatment of acute hepatic porphyria targeting the first and rate-limiting δ-aminolevulinic acid synthase 1 (ALAS1) enzyme of heme biosynthetic pathway. We described a 72-year old patient who presented with severe inaugural neurological form of acute intermittent porphyria evolving for several years which made her eligible for givosiran administration. On initiation of treatment, the patient developed a major hyperhomocysteinemia (>400 μmol/L) which necessitated to discontinue the siRNA-based therapy. A thorough metabolic analysis in the patient suggests that hyperhomocysteinemia could be attributed to a functional deficiency of cystathionine β-synthase (CBS) enzyme induced by givosiran. Long-term treatment with vitamin B 6 , a cofactor of CBS, allowed to normalize homocysteinemia while givosiran treatment was maintained. We review the recently published cases of hyperhomocysteinemia in acute hepatic porphyria and its exacerbation under givosiran therapy. We also discuss the benefits of vitamin B 6 supplementation in the light of hypothetic pathophysiological mechanisms responsible for hyperhomocysteinemia in these patients. Our results confirmed the importance of monitoring homocysteine metabolism and vitamin status in patients with acute intermittent porphyria in order to improve management by appropriate vitamin supplementation during givosiran treatment., Competing Interests: Pr. Patrick Mercie received fees for his participation in an advisory board for Alnylam Pharmaceuticals (France)., (© 2024 The Authors.)

Background: Cryopyrin-associated periodic syndrome (CAPS) is associated with NLRP3 pathogenic variants, mostly located in the NACHT (neuronal apoptosis inhibitor protein, MHC class 2 transcription activator, incompatibility locus protein from Podospora anserina, telomerase-associated protein) domain. Cold-induced urticarial rash is among the main clinical features. However, this study identified a series of 14 patients with pathogenic variants of the Y861 residue (p.Tyr861) of the LRR domain of NLRP3 and minimal prevalence of cold-induced urticarial rash., Objectives: This study aimed to address a possible genotype/phenotype correlation for patients with CAPS and to investigate at the cellular levels the impact of the Y861C substitution (p.Tyr861Cys) on NLRP3 activation., Methods: Clinical features of 14 patients with CAPS and heterozygous substitution at position 861 in the LRR domain of NLRP3 were compared to clinical features of 48 patients with CAPS and pathogenic variants outside the LRR domain of NLRP3. IL-1β secretion by PBMCs and purified monocytes from patients and healthy donors was evaluated following LPS and monosodium urate crystal stimulation., Results: Patients with substitution at position 861 of NLRP3 demonstrated a higher prevalence of sensorineural hearing loss while being less prone to skin urticarial. In contrast to patients with classical CAPS, cells from patients with a pathogenic variant at position 861 required an activation signal to secrete IL-1β but produced more IL-1β during the early and late phase of secretion than cells from healthy donors., Conclusions: Pathogenic variants of Y861 of NLRP3 drive a boost-dependent oversecretion of IL-1β associated with an atypical CAPS phenotype., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Little is known about localized osteoarticular Scedosporiosis (LOS). Most data come from case reports and small case series. Here we present an ancillary study of the nationwide French Scedosporiosis Observational Study (SOS), describing 15 consecutive cases of LOS diagnosed between January 2005 and March 2017. Adult patients diagnosed with LOS defined by osteoarticular involvement without distant foci reported in SOS were included. Fifteen LOS were analyzed. Seven patients had underlying disease. Fourteen patients had prior trauma as potential inoculation. Clinical presentation was arthritis (n = 8), osteitis (n = 5), and thoracic wall infection (n = 2). The most common clinical manifestation was pain (n = 9), followed by localized swelling (n = 7), cutaneous fistulization (n = 7), and fever (n = 5). The species involved were Scedosporium apiospermum (n = 8), S. boydii (n = 3), S. dehoogii (n = 1), and Lomentospora prolificans (n = 3). The species distribution was unremarkable except for S. boydii, which was associated with healthcare-related inoculations. Management was based on medical and surgical treatment for 13 patients. Fourteen patients received antifungal treatment for a median duration of 7 months. No patients died during follow-up. LOS exclusively occurred in the context of inoculation or systemic predisposing factors. It has a non-specific clinical presentation and is associated with an overall good clinical outcome, provided there is a prolonged course of antifungal therapy and adequate surgical management., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Scedosporiosis/lomentosporiosis is a devastating emerging fungal infection. Our objective was to describe the clinical pattern and to analyze whether taxonomic grouping of the species involved was supported by differences in terms of clinical presentations or outcomes. We retrospectively studied cases of invasive scedosporiosis in France from 2005 through 2017 based on isolates characterized by polyphasic approach. We recorded 90 cases, mainly related to Scedosporium apiospermum (n = 48), S. boydii/S. ellipsoideum (n = 20), and Lomentospora prolificans (n = 14). One-third of infections were disseminated, with unexpectedly high rates of cerebral (41%) and cardiovascular (31%) involvement. In light of recent Scedosporium taxonomic revisions, we aimed to study the clinical significance of Scedosporium species identification and report for the first time contrasting clinical presentations between infections caused S. apiospermum, which were associated with malignancies and cutaneous involvement in disseminated infections, and infections caused by S. boydii, which were associated with solid organ transplantation, cerebral infections, fungemia, and early death. The clinical presentation of L. prolificans also differed from that of other species, involving more neutropenic patients, breakthrough infections, fungemia, and disseminated infections. Neutropenia, dissemination, and lack of antifungal prescription were all associated with 3-month mortality. Our data support the distinction between S. apiospermum and S. boydii and between L. prolificans and Scedosporium sp. Our results also underline the importance of the workup to assess dissemination, including cardiovascular system and brain., (© The Author(s) 2020. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Chronic mucocutaneous candidiasis (CMC) is defined as recurrent or persistent infection of the skin, nails, and/or mucosae with commensal Candida species. The first genetic etiology of isolated CMC-autosomal recessive (AR) IL-17 receptor A (IL-17RA) deficiency-was reported in 2011, in a single patient. We report here 21 patients with complete AR IL-17RA deficiency, including this first patient. Each patient is homozygous for 1 of 12 different IL-17RA alleles, 8 of which create a premature stop codon upstream from the transmembrane domain and have been predicted and/or shown to prevent expression of the receptor on the surface of circulating leukocytes and dermal fibroblasts. Three other mutant alleles create a premature stop codon downstream from the transmembrane domain, one of which encodes a surface-expressed receptor. Finally, the only known missense allele (p.D387N) also encodes a surface-expressed receptor. All of the alleles tested abolish cellular responses to IL-17A and -17F homodimers and heterodimers in fibroblasts and to IL-17E/IL-25 in leukocytes. The patients are currently aged from 2 to 35 y and originate from 12 unrelated kindreds. All had their first CMC episode by 6 mo of age. Fourteen patients presented various forms of staphylococcal skin disease. Eight were also prone to various bacterial infections of the respiratory tract. Human IL-17RA is, thus, essential for mucocutaneous immunity to Candida and Staphylococcus, but otherwise largely redundant. A diagnosis of AR IL-17RA deficiency should be considered in children or adults with CMC, cutaneous staphylococcal disease, or both, even if IL-17RA is detected on the cell surface., Competing Interests: The authors declare no conflict of interest.

This study examines the laboratory aspects of diagnosis of coccidioidomycosis in 11 patients with acquired immunodeficiency syndrome (AIDS) and the qualitative and quantitative differences between host responses of AIDS and non-AIDS patients who died with disseminated coccidioidomycosis. Material obtained at bronchoscopy confirmed the diagnosis of pulmonary coccidioidomycosis in 67% (6/9) of the patients. Patients with AIDS had a generally poor granulomatous response and statistically significantly increased numbers of spherules in lung tissue compared with non-AIDS patients. Neither antifungal therapy nor duration of clinical disease influenced the number of organisms present. The findings suggest a parallel between AIDS-associated coccidioidomycosis and other granulomatous diseases such as leprosy and schistosomiasis, in which the type of granuloma formation and organism numbers are influenced by the T-lymphocyte milieu.

Previous studies have suggested that coccidioidomycosis during pregnancy is a devastating illness associated with high maternal mortality. However, this concept recently has been challenged. We examined the incidence of coccidioidomycosis during pregnancy in Tucson, Arizona, an area endemic for this infection. After reviewing the records of three separate health care facilities, we found ten cases of coccidioidomycosis among 47,120 pregnancies. Nine of the ten women had no underlying disease. Seven were diagnosed with coccidioidomycosis during either the first or second trimester. Illness resolved in all seven. Three other patients were diagnosed during the first ten days postpartum. While infection was self-limited in one woman, two others developed severe disseminated coccidioidomycosis associated with meningitis. Despite this, there were no maternal deaths. Of eight deliveries, all were uncomplicated and produced healthy infants. In summary, diagnosing coccidioidomycosis during pregnancy is rare. Although we observed no maternal death, our experience suggests that women who develop coccidioidomycosis late in pregnancy are at risk for developing severe disseminated infection.