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Clinical Case Reports Jun 2024Autoimmune polyglandular syndrome type 1 (APS-1) is a rare disorder defined by the presence of at least two of the following conditions: chronic mucocutaneous...
KEY CLINICAL MESSAGE
Autoimmune polyglandular syndrome type 1 (APS-1) is a rare disorder defined by the presence of at least two of the following conditions: chronic mucocutaneous candidiasis (CMC), chronic hypoparathyroidism, and Addison's syndrome. Despite the lack of CMC and autoimmune history, APS-1 can be diagnosed using genetic testing.
UNLABELLED
We present the case of a 28-year-old female patient with a history of hypocalcemia due to hypoparathyroidism since the age of 2 years. She presented to the endocrine clinic with hypogonadism, primary amenorrhea, and primary ovarian insufficiency. Addison's disease was eventually diagnosed, despite a negative Synacthen test. The adrenal crisis required intravenous hydrocortisone therapy. No CMC was documented, and there was no family history of such conditions. The diagnosis of APS-1 was confirmed by genetic testing, revealing homozygous pathogenic variants of the autoimmune regulator gene. Management included oral calcium and calcitriol and oral hydrocortisone and fludrocortisone for Addison's disease. Hormonal induction of secondary sexual characteristics was initiated. The patient received combined oral estrogen and progesterone pills. This case highlights the critical significance of early recognition, thorough evaluation, and tailored treatment for patients with APS-1 to enhance their quality of life and mitigate potentially life-threatening complications. This underscores the importance of screening for associated minor autoimmune diseases as part of a holistic approach to care.
PubMed: 38808199
DOI: 10.1002/ccr3.9015 -
Georgian Medical News Mar 2024Aim - to improve the methodology for collecting material from lesions of the oral mucosa for exfoliative cytological examination. A group of patients diagnosed with...
Aim - to improve the methodology for collecting material from lesions of the oral mucosa for exfoliative cytological examination. A group of patients diagnosed with B37.0 Candida stomatitis was examined. To clarify the diagnosis, various methods of collecting biological material from the tongue of patients were used, namely, the method using a cytobrush with subsequent fixation of cytological material on a slide. The microbiota of the back of the tongue was analyzed in 12 patients with glossitis and 12 healthy subjects (the control group). The microscopic method of research was used - using an immersion microscope MICROmed@XS-3330, and the morphological and tinctorial properties of microorganisms were determined. In ten fields of view, the number of leukocytes, the nature of epithelial cells, and the presence of various microorganisms were detected and counted. A comparison of the quality of the use of the microscope method for the study of the tongue microbiota of patients with candidal glossitis was performed under the conditions of taking pathological material using a dental scalpel and an oral cytobrush. For a reasonable interpretation of the results and determination of their significance, a statistical analysis was performed to determine the frequency of detection of microorganisms in patients with glossitis and healthy subjects, depending on the nature of the material taken from the back of the tongue using a dental scalpel or cytobrush. The studies showed that the etiologic structure of glossitis pathogens was dominated by Candida yeast-like fungi, but cases of leptotrichosis aetiology were observed (16.7%). Monococci and gram-negative monobacteria were detected in all studied groups. An increase in the diversity of microorganisms was found when the material was taken with a cytobrush. The microbiota of all subjects differed depending on the type of instrument used for sampling. Thus, in the group of healthy individuals, the interdental brush helped to detect twice as many streptococci as a scalpel. In patients with candidiasis, a brush biopsy showed a 2.7-fold increase in gram-positive diplococci, twice as many streptococci and gram-positive bacilli, three times as many staphylococci, 2.25 times as many clusterforming gram-negative cocci, and 2.3 times as many gram-negative diplococci. A significant increase in the diversity of microorganisms was observed with the cytobrush compared to the use of a dental scalpel. In patients with glossitis, the accumulation of keratinized epithelial cells was significantly higher compared to the presence of young cells in healthy subjects, regardless of the method of sampling.
Topics: Humans; Mouth Mucosa; Tongue; Candida; Male; Female; Microbiota; Glossitis; Adult; Biocompatible Materials; Specimen Handling; Candidiasis, Oral; Case-Control Studies; Middle Aged
PubMed: 38807402
DOI: No ID Found -
Open Biology May 2024is an important pathogen causing invasive infection associated with a high mortality rate. One mechanism that causes the failure of eradication is an increase in...
is an important pathogen causing invasive infection associated with a high mortality rate. One mechanism that causes the failure of eradication is an increase in regulatory T cells (Treg), which play a major role in immune suppression and promoting pathogenicity. To date, how induces a Treg response remains unclear. Dendritic cells (DCs) recognition of fungi provides the fundamental signal determining the fate of the T-cell response. This study investigated the interplay between and DCs and its effect on Treg induction. We found that β-glucan was a major component that interacted with DCs and consequently mediated the Treg response. Blocking the binding of β-glucan to dectin-1 and complement receptor 3 (CR3) showed that CR3 activation in DCs was crucial for the induction of Treg. Furthermore, a ligand-receptor binding assay showed the preferential binding of β-glucan to CR3. Our data suggest that β-glucan potentially mediates the Treg response, probably through CR3-dependent activation in DCs. This study contributes new insights into immune modulation by that may lead to a better design of novel immunotherapeutic strategies for invasive infection.
Topics: Candida glabrata; Dendritic Cells; T-Lymphocytes, Regulatory; beta-Glucans; Animals; Macrophage-1 Antigen; Mice; Lectins, C-Type; Candidiasis; Mice, Inbred C57BL
PubMed: 38806144
DOI: 10.1098/rsob.230315 -
Journal of Oral and Maxillofacial... 2024The Bellary district in Karnataka, rich in mineral resources, is a major mining industry, but prolonged exposure to mining can lead to health hazards. The study aims to...
BACKGROUND
The Bellary district in Karnataka, rich in mineral resources, is a major mining industry, but prolonged exposure to mining can lead to health hazards. The study aims to assess the genotoxic impact of mining pollutants on mine workers using the micro-nucleus (MN) assay.
SETTING AND DESIGN
Cross-sectional study.
MATERIALS AND METHODS
A total of 250 individuals (198 males and 52 females) working in mining areas were examined, and their oral findings were recorded in a proforma. For the micro-nucleus assay, buccal smears from 30 individuals working in mining areas with habits, 30 individuals working in mining areas without habits, and 30 individuals residing in non-mining areas (control group) were selected. Smears were stained with Giemsa stain to identity and quantify the MNs.
RESULTS
The frequency of oral mucosal problems among 250 persons working in mining regions was 170 (68.0%) with no oral mucosal conditions, 79 (32.6%) with oral mucosal conditions, 25 (10%) with leukoplakia, 1 (0.4%) with lichen planus, and 8 (3.2%) with ulcerations. Acute necrotising gingivitis was reported in one person (0.4%), candidiasis in two (0.8%), abscess in two (0.8%), OSMF in 39 (15.6%), and oral cancer in two (0.8%). The mean MN count was 2.40 + 1.57 in mine employees with habits, 2.18 + 1.25 in mine workers without habits, and 1.40 + 0.55 in normal healthy controls.
CONCLUSION
Reduced occupational health risks brought on by exposure to mining contaminants require protective measures. After being exposed to mining pollutants, exfoliated buccal mucosal cells can be examined for genotoxicity.
PubMed: 38800431
DOI: 10.4103/jomfp.jomfp_414_23 -
BioRxiv : the Preprint Server For... Jun 2024SARS-CoV-2 targets salivary glands potentially impacting oral health. We show that presence of replicating viruses in the acinar cells of salivary glands compromises...
SARS-CoV-2 targets salivary glands potentially impacting oral health. We show that presence of replicating viruses in the acinar cells of salivary glands compromises production and secretion of histatin-5, a key host-produced antifungal peptide. The salivary levels of histatin-5 were significantly reduced in SARS-CoV-2 infected subjects, concomitant with enhanced prevalence of the fungal opportunistic pathogen Candida albicans. These findings provide direct evidence associating SARS-CoV-2 infection with predisposition to oral candidiasis.
PubMed: 38798323
DOI: 10.1101/2024.05.13.593942 -
Discovery Medicine May 2024The number of chronic kidney disease (CKD) patients requiring renal replacement therapy is increasing, often exhibiting oral manifestations including periodontal... (Review)
Review
The number of chronic kidney disease (CKD) patients requiring renal replacement therapy is increasing, often exhibiting oral manifestations including periodontal disease, gingival hyperplasia, altered saliva composition, and uremic stomatitis. Uremic stomatitis, xerostomia, and candidiasis are very frequent, particularly among patients undergoing dialysis or kidney transplant recipients. CKD patients also experience profound alterations in bone metabolism inherent in the homeostasis of calcium, phosphorus, vitamin D, parathyroid hormone, and fibroblast growth factor (FGF). These alterations lead to demineralization of the jaw bones, reduced bone trabeculae, reduced cortical bone thickness, fibrocystic bone lesions, bone fractures, and delayed wound healing post-tooth extraction. Consequently, oral health management of elderly hemodialysis patients poses serious clinical problems. This review focused on the oral health and rehabilitation of patients with CKD or on dialysis.
Topics: Humans; Oral Health; Renal Insufficiency, Chronic; Dental Implants; Oral Surgical Procedures; Renal Dialysis
PubMed: 38798248
DOI: 10.24976/Discov.Med.202436184.82 -
The Lancet. Haematology Jun 2024Follicular helper T-cell lymphomas (TFHL) harbour frequent alterations in genes that regulate DNA methylation. Preliminary reports suggest that treatment with... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
Oral azacitidine compared with standard therapy in patients with relapsed or refractory follicular helper T-cell lymphoma (ORACLE): an open-label randomised, phase 3 study.
BACKGROUND
Follicular helper T-cell lymphomas (TFHL) harbour frequent alterations in genes that regulate DNA methylation. Preliminary reports suggest that treatment with 5-azacitidine has clinical activity in patients with relapsed or refractory TFHL. We aimed to compare the oral form of azacitidine with investigator's choice standard therapy (ICT; ie, gemcitabine, bendamustine, or romidepsin) in patients with relapsed or refractory TFHL.
METHODS
Patients older than 18 years with relapsed or refractory TFHL (angioimmunoblastic T-cell lymphoma, follicular lymphoma, or nodal T-cell lymphoma with phenotype, ie, positive with two or more markers among CD10, BCL6, CXCL13, PD1, or ICOS) based on the 2017 WHO classification of haematological neoplasms, with an Eastern Cooperative Oncology Group performance status score of 0-3, were recruited in university hospitals from five European countries and from Japan. Patients were randomly assigned 1:1 to treatment with either azacitidine given at a dose of 300 mg once a day (200 mg in Japanese patients) for 14 days in a 28-day cycle or gemcitabine, bendamustine, or romidepsin according to the investigator's choice. Random assignment was stratified by the number of previous lines of therapy and by the presence of previous or concomitant myeloid malignancy. The primary endpoint was investigator-assessed progression-free survival, presented in the intention-to-treat population. This Article is the final analysis of this trial, registered at ClinicalTrials.gov (Europe NCT03593018 and Japan NCT03703375).
FINDINGS
86 patients (median age 69 years [IQR 62-76], 50 patients were male, 36 were female) were enrolled between Nov 9, 2018, to Feb 22, 2021; 42 in the azacitidine group and 44 in the ICT group. With a median follow-up of 27·4 months (IQR 20·2-32·9), the median progression-free survival was 5·6 months (95% CI 2·7 -8·1) in the azacitidine group versus 2·8 months (1·9-4·8) in the ICT group (hazard ratio of 0·63 (95% CI 0·38-1·07); 1-sided p=0·042). Grade 3-4 adverse events were reported in 32 (76%) of 42 patients in the azacitidine group versus 42 (98%) of 43 patients in the ICT group. The most adverse grade 3 or worse adverse events were haematological (28 [67%] of 42 patients vs 40 [93%] of 43 patients), infection (8 [19%] and 14 [33%]), and gastrointestinal (5 [12%] vs 1 [2%] for azacitidine and ICT, respectively). There were two treatment-related deaths in the azacitidine group (one endocarditis and one candidiasis) and three in the ICT group (one heart failure, one COVID-19, and one cause unknown).
INTERPRETATION
Although the pre-specified primary outcome of the trial was not met, the favourable safety profile suggests that azacitidine could add to the treatment options in these difficult to treat diseases especially in combination with other drugs. Trials with combination are in preparation in a platform trial.
FUNDING
Bristol-Myers Squibb.
TRANSLATION
For the French translation of the abstract see Supplementary Materials section.
Topics: Humans; Male; Female; Aged; Middle Aged; Azacitidine; Administration, Oral; Bendamustine Hydrochloride; Gemcitabine; Lymphoma, Follicular; Deoxycytidine; Depsipeptides; Antineoplastic Combined Chemotherapy Protocols; Antimetabolites, Antineoplastic; Aged, 80 and over
PubMed: 38796193
DOI: 10.1016/S2352-3026(24)00102-9 -
Lancet (London, England) Jun 2024Patients with hidradenitis suppurativa have substantial unmet clinical needs and scarce therapeutic options. We aimed to assess the efficacy and safety of bimekizumab, a... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and safety of bimekizumab in patients with moderate-to-severe hidradenitis suppurativa (BE HEARD I and BE HEARD II): two 48-week, randomised, double-blind, placebo-controlled, multicentre phase 3 trials.
BACKGROUND
Patients with hidradenitis suppurativa have substantial unmet clinical needs and scarce therapeutic options. We aimed to assess the efficacy and safety of bimekizumab, a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F and IL-17A, in patients with moderate-to-severe hidradenitis suppurativa.
METHODS
BE HEARD I and II were two identically designed, 48-week randomised, double-blind, placebo-controlled, multicentre phase 3 trials. Patients aged 18 years or older with moderate-to-severe hidradenitis suppurativa were randomly assigned 2:2:2:1 using interactive response technology (stratified by worst Hurley Stage at baseline and baseline systemic antibiotic use) to receive subcutaneous bimekizumab 320 mg every 2 weeks; bimekizumab 320 mg every 2 weeks to week 16, then every 4 weeks to week 48; bimekizumab 320 mg every 4 weeks to week 48; or placebo to week 16, then bimekizumab 320 mg every 2 weeks. The primary outcome was an hidradenitis suppurativa clinical response of at least 50%, defined as a reduction in total abscess and inflammatory nodule count of at least 50% from baseline with no increase from baseline in abscess or draining tunnel count (HiSCR50) at week 16. Efficacy analyses included all randomly assigned study patients (intention-to-treat population). Safety analyses included all patients who received at least one full or partial dose of study treatment in the safety set, and of bimekizumab in the active-medication set. These trials are registered at ClinicalTrials.gov, NCT04242446 and NCT04242498, and both are completed.
FINDINGS
Patients for BE HEARD I were recruited from Feb 19, 2020, to Oct 27, 2021, and 505 patients were enrolled and randomly assigned. Patients for BE HEARD II were recruited from March 2, 2020, to July 28, 2021, and 509 patients were enrolled and randomly assigned. The primary outcome at week 16 was met in the group who received bimekizumab every 2 weeks using modified non-responder imputation; higher responder rates were observed with bimekizumab versus placebo in both trials: 138 (48%) of 289 patients versus 21 (29%) of 72 patients in BE HEARD I (odds ratio [OR] 2·23 [97·5% CI 1·16-4·31]; p=0·0060) and 151 (52%) of 291 patients versus 24 (32%) of 74 patients in BE HEARD II (2·29 [1·22-4·29]; p=0·0032). In BE HEARD II, HiSCR50 was also met in the group who were administered bimekizumab every 4 weeks (77 [54%] of 144 vs 24 [32%] of 74 with placebo; 2·42 [1·22-4·80]; p=0·0038). Responses were maintained or increased to week 48. Serious treatment-emergent adverse events were reported in 40 (8%) patients in BE HEARD I and in 24 (5%) patients in BE HEARD II treated with bimekizumab over 48 weeks. The most frequently reported treatment-emergent adverse events to week 48 were hidradenitis in both trials, in addition to coronavirus infection and diarrhoea in BE HEARD I, and oral candidiasis and headache in BE HEARD II. One death was reported across the two trials, and was due to congestive heart failure in a patient with substantial cardiovascular history treated with bimekizumab every 2 weeks in BE HEARD I (considered unrelated to bimekizumab treatment by the investigator). No new safety signals were observed.
INTERPRETATION
Bimekizumab was well tolerated by patients with hidradenitis suppurativa and produced rapid and deep clinically meaningful responses that were maintained up to 48 weeks. Data from these two trials support the use of bimekizumab for the treatment of patients with moderate-to-severe hidradenitis suppurativa.
FUNDING
UCB Pharma.
Topics: Humans; Hidradenitis Suppurativa; Double-Blind Method; Male; Female; Adult; Middle Aged; Treatment Outcome; Antibodies, Monoclonal, Humanized; Severity of Illness Index; Interleukin-17
PubMed: 38795716
DOI: 10.1016/S0140-6736(24)00101-6 -
Archives of Oral Biology Aug 2024This study investigated C. albicans strain diversity and maintenance in the oral cavity of HIV positive women over a 6 month period.
OBJECTIVE
This study investigated C. albicans strain diversity and maintenance in the oral cavity of HIV positive women over a 6 month period.
STUDY DESIGN
C. albicans strains were isolated from 17 HIV positive women at Charlotte Maxeke Academic Hospital, Johannesburg at 3 intervals over a 6 month period. Strains were genotyped using ABC and Multilocus Sequence Typing (MLST) techniques. In the MLST technique, for each strain, a Diploid Sequence Type (DST) number was obtained. Using cluster analysis, an Unweighted Pair Group Method with Arithmetic Mean (UPGMA) dendrogram and a matrix of strain similarities were generated. Strains were also compared to the previous South African isolates documented in the MLST database.
RESULTS
Ninety four percent of women carried the same ABC genotype for 6 months. MLST technique, showed that ten women (58.8%) carried the same DST at 2 visits, while seven (41.2%) carried different DST at all visits. Further analysis showed that 64.7% of women were recolonised with different strains and 35.3% carried the same strains of C. albicans with heterozygosity. A total of 40 diploid sequence types were identified of which 27 DSTs were unique to this study group that were added to the MLST database. Most of the strains were closely related to previously isolated strains from South Africa.
CONCLUSION
Recolonization of the oral cavity with different strains and microevolution of the original strains of C. albicans can occur, which can be a potential problem for HIV patients, in whom highly virulent and drug resistant strains can emerge.
Topics: Humans; Female; South Africa; Candida albicans; Adult; Multilocus Sequence Typing; Candidiasis, Oral; Genotype; HIV Infections; Mouth; Genetic Variation; Mycological Typing Techniques; Middle Aged
PubMed: 38795522
DOI: 10.1016/j.archoralbio.2024.106007 -
International Journal of Molecular... May 2024Fluconazole (FZ) is a potential antifungal compound for treating superficial and systemic candidiasis. However, the use of conventional oral drug products has some...
Fluconazole (FZ) is a potential antifungal compound for treating superficial and systemic candidiasis. However, the use of conventional oral drug products has some limitations. The development of buccal film may be a potential alternative to oral formulations for FZ delivery. The present study involved the development of novel FZ-loaded solid lipid nanoparticles (FZ-SLNs) in pectin solutions and the investigation of their particle characteristics. The particle sizes of the obtained FZ-SLNs were in the nanoscale range. To produce pectin films with FZ-SLNs, four formulations were selected based on the small particle size of FZ-SLNs and their suitable polydispersity index. The mean particle sizes of all chosen FZ-SLNs formulations did not exceed 131.7 nm, and the mean polydispersity index of each formulation was less than 0.5. The properties of films containing FZ-SLNs were then assessed. The preparation of all FZ-SLN-loaded pectin films provided the mucoadhesive matrices. The evaluation of mechanical properties unveiled the influence of particle size variation in FZ-SLNs on the integrity of the film. The Fourier-transform infrared spectra indicated that hydrogen bonds could potentially form between the pectin-based matrix and the constituents of FZ-SLNs. The differential scanning calorimetry thermogram of each pectin film with FZ-SLNs revealed that the formulation was thermally stable and behaved in a solid state at 37 °C. According to a drug release study, a sustained drug release pattern with a burst in the initial stage for all films may be advantageous for reducing the lag period of drug release. All prepared films with FZ-SLNs provided a sustained release of FZ over 6 h. The films containing FZ-SLNs with a small particle size provided good permeability across the porcine mucosa. All film samples demonstrated antifungal properties. These results suggest the potential utility of pectin films incorporating FZ-SLNs for buccal administration.
Topics: Pectins; Nanoparticles; Fluconazole; Particle Size; Antifungal Agents; Administration, Buccal; Lipids; Drug Carriers; Drug Liberation; Spectroscopy, Fourier Transform Infrared; Drug Delivery Systems; Mouth Mucosa; Calorimetry, Differential Scanning; Animals; Liposomes
PubMed: 38791451
DOI: 10.3390/ijms25105413