Search Results (353)

Invasive aspergillosis is a rare but severe fungal infection primarily affecting immunocompromised individuals. The Coronavirus Disease-2019 (COVID-19) pandemic has introduced new complexities in managing aspergillosis due to the widespread use of corticosteroids for treating COVID-19-related respiratory distress, which can increase susceptibility to fungal infections. Here, we present a challenging case of progressive cerebral aspergillosis complicated by cavernous sinus thrombosis (CST) in a 67-year-old male with a history of COVID-19. The patient, initially misdiagnosed with temporal arteritis, received pulse corticosteroid therapy twice before presenting with persistent left-sided headaches and vision loss. Cranial imaging revealed findings consistent with fungal sinusitis, Tolosa–Hunt syndrome, and orbital pseudotumor, which progressed despite initial antifungal therapy. Subsequent magnetic resonance imaging indicated an invasive mass extending into the left cavernous sinus and other intracranial structures, raising suspicion of aspergillosis. A transsphenoidal biopsy confirmed Aspergillus infection, leading to voriconazole therapy. Despite aggressive treatment, follow-up imaging revealed significant progression, with extension to the right frontal region and left cavernous sinus. The patient then developed visual impairment in the right eye and was diagnosed with CST secondary to fungal sinusitis. Management included a combination of systemic antifungals and antibiotics; however, the patient declined surgical intervention. This case underscores the diagnostic challenges and rapid progression associated with cerebral aspergillosis in post-COVID-19 patients treated with corticosteroids. This report highlights the need for heightened clinical suspicion and prompt, targeted interventions in similar cases to improve patient outcomes. Further research is required to understand the optimal management of invasive fungal infections. Full article

Cutaneous mycoses are common infections whose treatment has become more complex due to increasing antifungal resistance and the need for prolonged therapies, hindering patient adherence and increasing the incidence of adverse effects. Consequently, the use of physical therapies, especially photodynamic therapy (PDT), has increased for the treatment of onychomycosis due to its antimicrobial capacity being mediated by the production of reactive oxygen species. This study investigates the in vitro effect of applying blue light (448 nm) or red light (645 nm), alone or together with terbinafine, on the viability of human keratinocytes and the production of reactive oxygen species. The combination of terbinafine and blue light significantly increases ROS production and caspase-3 expression, while red light together with terbinafine increases catalase, superoxide dismutase (SOD) and PPARγ expression, which reduces the amount of ROS in the cultures. The effect of both treatments could be useful in clinical practice to improve the response of cutaneous mycoses to pharmacological treatment, reduce their toxicity and shorten their duration. Full article

Background: Analysis of T-cell receptor (TCR) clonality is a major diagnostic tool for lymphomas, particularly for cutaneous T-cell lymphomas (CTCL) like Mycosis fungoides and Sézary syndrome. However, a fast and cost-effective workflow is needed to enable widespread use of this method. Methods: We established a procedure for TCR rearrangement analysis via Oxford Nanopore Technology (ONT) sequencing. TCR receptor rearrangements (TCR-gamma and TCR-beta chains) were analyzed in samples from 45 patients with various diagnoses: Mycosis fungoides (37/45), Sézary Syndrome (2/45), folliculotropic CTCL (1/45), and non-CTCL diagnoses as polyclonal controls (5/45). Sample types included formalin-fixed paraffin-embedded (FFPE) samples (27/45), fresh frozen samples (9/45), and CD3-isolated cells (9/45). In addition, DNA of a Jurkat cell line was used as a monoclonal control. TCR amplicons were generated employing an optimized version of the protocol from the Euro Clonality consortium. Sequencing was conducted on the ONT GridION and Illumina MiSeq platforms, followed by similar bioinformatic analysis protocols. The tumor clone frequency (TCF), a crucial prognostic factor for CTCL patients, was used for method comparison. Results: The use of an optimized amplicon protocol and adapted bioinformatic tools demonstrated a strong correlation in TCF values between both sequencing methods across all sample types (range R: 0.992–0.996; range r²: 0.984–0.991). Conclusions: In summary, ONT sequencing was able to detect TCR clonality comparable to NGS, indicating its potential as a faster and more cost-effective option for routine diagnostic use. Full article

Mycosis fungoides (MF) is the most prevalent type of cutaneous T cell lymphomas. Studies on the prognosis of MF are limited, and no research exists on the potential of artificial intelligence to predict MF prognosis. This study aimed to compare the predictive capabilities of various machine learning (ML) algorithms in predicting progression, treatment response, and relapse and to assess their predictive power against that of the Cox proportional hazards (CPH) model in patients with early-stage MF. The data of patients aged 18 years and over who were diagnosed with early-stage MF at Ankara University Faculty of Medicine Hospital from 2006 to 2024 were retrospectively reviewed. ML algorithms were utilized to predict complete response, relapse, and disease progression using patient data. Of the 185 patients, 94 (50.8%) were female, and 91 (49.2%) were male. Complete response was observed in 114 patients (61.6%), while relapse and progression occurred in 69 (37.3%) and 54 (29.2%) patients, respectively. For predicting progression, the Support Vector Machine (SVM) algorithm demonstrated the highest success rate, with an accuracy of 75%, outperforming the CPH model (C-index: 0.652 for SVM vs. 0.501 for CPH). The most successful model for predicting complete response was the Ensemble model, with an accuracy of 68.89%, surpassing the CPH model (C-index: 0.662 for the Ensemble model vs. 0.543 for CPH). For predicting relapse, the decision tree classifier showed the highest performance, with an accuracy of 78.17%, outperforming the CPH model (C-index: 0.782 for the decision tree classifier vs. 0.505 for CPH). The results suggest that ML algorithms may be useful in predicting prognosis in early-stage MF patients. Full article

Like other organisms, fungi produce extracellular vesicles (EVs) that are involved in various biological processes, including intercellular communication and the transport of molecules between cells. These EVs can be applied in fungal pathogenesis, virulence, and interactions with other organisms, including host cells, in the case of fungal infections. While some types of mycoses are relatively common and easily treatable, certain neglected mycoses pose significant public health challenges, such as sporotrichosis, chromoblastomycosis, and paracoccidioidomycosis. These infectious diseases can cause significant morbidity and disability, leading to a reduced quality of life for the patients. So, research about the virulence factor is essential to understand how fungi escape the immune system. In this context, this manuscript reviews the study of fungal EVs, their cargo, how they are obtained, and their role during the infectious process, which is extremely important for understanding this neglected mycosis. Full article

The high cancer burden in the Middle East and North Africa (MENA region) is coupled with an increasing cancer incidence. While the MENA region constitutes 6% of the world’s population, it remains underrepresented in clinical trials. Cutaneous T-cell lymphomas (CTCLs) represent a heterogeneous group of rare extranodal non-Hodgkin lymphomas with variable clinical presentation. In the MENA region, where darker skin colors are more common than in the West, CTCL generally presents at a younger age and with distinct clinical features that necessitate special expertise and management across disciplines: rare forms of CTCL are more common (hypo- and hyperpigmented MF) and a higher prevalence of pediatric MF is noticed. The multidisciplinary approach to cancer management is growing worldwide and is necessary for the comprehensive management of CTCL. The MENA CTCL group was established with the aim of creating a collaborative environment for the diagnosis and treatment of CTCL in the region. Its first meeting was held in May 2023. The group plans to increase the global representation of the MENA region and establish CTCL registries and patient advocacy groups in the region. Full article

Cutaneous T cell lymphomas (CTCLs) are a heterogeneous group of non-Hodgkin lymphomas, with mycosis fungoides and Sézary syndrome being the two common subtypes. Despite the substantial improvement in early-stage diagnosis and treatments, some patients still progress to the advanced stage with an elusive underpinning mechanism. While this unsubstantiated disease mechanism coupled with diverse clinical outcomes poses challenges in disease management, emerging evidence has implicated the tumor microenvironment in the disease process, thus revealing a promising therapeutic potential of targeting the tumor microenvironment. Notably, malignant T cells can shape their microenvironment to dampen antitumor immunity, leading to Th2-dominated responses that promote tumor progression. This is largely orchestrated by alterations in cytokines expression patterns, genetic dysregulations, inhibitory effects of immune checkpoint molecules, and immunosuppressive cells. Herein, the recent insights into the determining factors in the CTCL tumor microenvironment that support their progression have been highlighted. Also, recent advances in strategies to target the CTCL tumor micromovement with the rationale of improving treatment efficacy have been discussed. Full article

Dermatophytosis in cattle is most often caused by infection with Trichophyton verrucosum (T. verrucosum), but also with Trichophyton rubrum (T. rubrum), Trichophyton mentagrophytes (T. mentagrophytes) and others, regardless of the geographical zone. The infection is transmitted through direct contact between animals as well as infected environmental elements. The human-to-human transmission of fungal infection is also possible.. This retrospective study was conducted based on a detailed analysis of the results of the mycological examination and medical documentation of 40 patients from Greater Poland, diagnosed with cattle-to-human dermatophytoses from March 2017 to November 2023. T. verrucosum accounted for 97.5% of infections and T. mentagrophytes for 2.5%; no other species of dermatophytes from cattle were found. Superficial skin mycosis in humans associated with cattle was more often diagnosed in small children and men directly engaged in cattle breeding. The dominant etiological factor of the superficial fungal skin infection was T. verrucosum, which mainly affected the scalp in children and upper limbs in adult men. In relation to the cattle population in Greater Poland, the number of cases of superficial skin mycoses among cattle breeders and their family members over the period of more than six and a half years of observation does not seem to be high. Full article

Onychomycosis is a common fungal nail infection for which new antifungals are needed to overcome antimicrobial resistance and the limitations of conventional treatments. This study reports the development of antifungal nail lacquers containing oregano essential oil (OEO), rosemary essential oil (REO), and biogenic silver nanoparticles (bioAgNPs). The formulations (F) were tested against dermatophytes using agar diffusion, ex vivo nail infection, and scanning electron microscopy techniques. They were evaluated for their pharmacotechnical characteristics and by FTIR-PAS to assess permeation across the nail. F-OEO and F-OEO/bioAgNPs were promising candidates for the final nail lacquer formulation, as they permeated through the nail and showed antifungal efficacy against dermatophytes-contaminated nails after 5 days of treatment. Treated nails exhibited decreased hyphae and spores compared to the untreated control; the hyphae were atypically flattened, indicating loss of cytoplasmic content due to damage to the cytoplasmic membrane. The formulations were stable after centrifugation and thermal stress, maintaining organoleptic and physicochemical characteristics. Both F-OEO and F-OEO/bioAgNPs had pH compatible with the nail and drying times (59–90 s) within the reference for nail lacquer. For the first time, OEO and bioAgNPs were incorporated into nail lacquer, resulting in a natural and nanotechnological product for onychomycosis that could combat microbial resistance. Full article

Patients with advanced-stage mycosis fungoides (MF IIB–IVB) and Sézary syndrome (SS) have poor prognoses, with survival ranging from 4.7 to 1.4 years depending on the disease stage. There is a need for therapeutic approaches that lead to long-lasting responses and improved quality of life and survival. Mogamulizumab, a humanized antibody against the CCR4 molecule, and low-dose total skin electron beam therapy (TSEBT) are two known established treatments for MF and SS as a monotherapy. However, little is known about the potential additive effect on the combination of both treatments. We report here for the first time the concurrent use of low-dose hypofractionated TSEBT (2 × 4 Gy) with mogamulizumab. Based on two relapsed/refractory and advanced-stage CTCL patients, we show that this combination may be well tolerated in advanced-stage MF or SS and may potentially lead to an additive treatment effect on response times, particularly in the skin and blood within two weeks. We propose that this combination may be a treatment option for patients with SS. Further research is needed to understand the efficacy and tolerability profile of this therapeutic combination and to determine if there is an additive effect of the combination on the response rates when compared with the monotherapy. Full article

Although the vast majority of CTCL subtypes are of the CD4+ T-helper cell differentiation phenotype, there is a spectrum of CD8+ variants that manifest wide-ranging clinical, histologic, and phenotypic features that inform the classification of the disease. CD8, like CD4, and cytotoxic molecules (including TIA and granzyme) are readily detectable via IHC staining of tissue and, when expressed on the phenotypically abnormal T-cell population, can help distinguish specific CTCL subtypes. Nonetheless, given that the histopathologic differential for CD8+ lymphoproliferative disorders and lymphomas may range from very indolent lymphomatoid papulosis (LyP) to aggressive entities like CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma (AECTCL), CD8 and/or cytotoxic molecule expression alone is insufficient for diagnosis and is not in itself an indicator of prognosis. We present a review of CTCL subtypes that can demonstrate CD8 positivity: CD8+ mycosis fungoides (MF), LyP type D, subcutaneous panniculitis-like T-cell lymphoma (SPTCL), primary cutaneous gamma/delta T-cell lymphoma (PCGDTL), CD8+ AECTCL, and acral CD8+ T-cell lymphoproliferative disorder (acral CD8+ TCLPD). These diseases may have different clinical manifestations and distinctive treatment algorithms. Due to the rare nature of these diseases, it is imperative to integrate clinical, histologic, and immunohistochemical findings to determine an accurate diagnosis and an appropriate treatment plan. Full article

The diagnosis of basal cell carcinoma (BCC) in dark phototypes can be a challenging task due to the lack of relevant clues and its variable presentation. In this regard, there is growing evidence that dermoscopy may benefit the recognition of BCC even for skin of color (SoC). The objective of this review is to provide an up-to-date overview on clinical and dermoscopic patterns of BCC in SoC, also comparing such findings with those of the main clinical mimickers reported in the literature. A comprehensive search of the literature through the PubMed electronic database was carried out in order to identify papers describing the clinical and dermoscopic features of BCC in dark phototypes (IV–VI). By finding macroscopic clinical presentations of BCCs in SoC patients and any possible clinical mimickers considered in the retrieved papers, we built a differential diagnosis list and analyzed the dermoscopic findings of such conditions to facilitate the diagnosis of BCC. BCC in darker skin may present as pigmented nodular lesions, pigmented patches or plaques, ulcers, erythematous nodular lesions, erythematous plaques or patches, or scar-like lesions, depending on its subtype and body site. The differential diagnosis for BCC in patients with SoC includes squamous cell carcinoma, melanoma, nevi, adnexal tumors and sebaceous keratosis. Additionally, it differs from that of Caucasians, as it also includes lesions less common in fair skin, such as dermatosis papulosa nigra, melanotrichoblastoma, and pigmented dermatofibrosarcoma protuberans, and excludes conditions like actinic keratosis and keratoacanthoma, which rarely appear in darker skin. The resulting differences also include infectious diseases such as deep cutaneous mycosis and inflammatory dermatoses. The most prevalent differentiating dermoscopic feature for BCC includes blue, black and gray dots, though arborizing vessels still remain the predominant BCC feature, even in dark phototypes. Diagnostic approach to BCC in dark-skinned patients varies due to the prevalence of dermoscopy findings associated with hyperpigmented structures. Clinicians should be aware of such points of differentiation for a proper management of this tumor in SoC. Full article

The controversially discussed taxonomy of the Cryptococcus neoformans/Cryptococcus gattii species complex encompasses at least eight major molecular types. Cerebral cryptococcomas are a common manifestation of cryptococcal neurological disease. In this study, we compared neurotypical symptoms and differential neurovirulence induced by one representative isolate for each of the eight molecular types studied. We compared single focal lesions caused by the different isolates and evaluated the potential relationships between the fungal burden and properties obtained with quantitative magnetic resonance imaging (qMRI) techniques such as diffusion MRI, T₂ relaxometry and magnetic resonance spectroscopy (MRS). We observed an inverse correlation between parametric data and lesion density, and we were able to monitor longitudinally biophysical properties of cryptococcomas induced by different molecular types. Because the MRI/MRS techniques are also clinically available, the same approach could be used to assess image-based biophysical properties that correlate with fungal cell density in lesions in patients to determine personalized treatments. Full article

Treatment with CCR-4 antagonists has been shown to be protective against the development of invasive pulmonary aspergillosis in animal models. Herein, we present a case of fatal invasive pulmonary aspergillosis in a patient receiving Mogamulizumab. A 64-year-old man with refractory mycosis fungoides was found to have diffuse bilateral pulmonary nodules during a chest CT in June 2022. Bronchoalveolar lavage (BAL) fungal and bacterial cultures and galactomannan were negative, as well as serum beta-glucan and galactomannan. Histology showed a lymphoid infiltrate with a negative fungal stain, so a presumptive diagnosis of lymphoma infiltration was made, and the patient started the CCR-4 antagonist Mogamulizumab treatment in August 2022. He had no symptoms until November when he presented to the hematology clinic reporting dyspnea. He had neutrophilic leukocytosis (18.610 cells/µL), his c-reactive protein was 27 mg/dL, and his skin lesions from mycosis fungoides were just starting to improve. A CT scan showed large diffuse bilateral severely necrotic cavitated lesions with thick walls and apparently synchronous evolution. Beta-glucan was 31 pg/mL (wako method), while serum galactomannan 3.6. BAL was positive for Aspergillus fumigatus culture and galactomannan. Patient started voriconazole but, despite being in a stable condition, he suddenly died after two days. Discussion: Paradoxically, worsening of the chronic pulmonary aspergillosis has been reported after nivolumab treatment, and immune reconstitution syndromes are usually seen during neutrophil recovery after intensive chemotherapy. Our patient already presented indolent lung lesions from 5 months before and he remained completely asymptomatic until the aspergillosis diagnosis when he quickly passed away. Even if a progression of the lesions was expected in 5 months, this case had an atypical presentation. During the 5-month period, he had no pulmonary symptoms, and his c-reactive protein was negative. Furthermore, in the setting of the natural progression of subacute/chronic aspergillosis, a different radiological picture was expected with a less severe and probably asynchronous evolution. We think that the immune restoration associated with Mogamulizumab (also supported by the concurrent clinical response of the skin lesions) could have been detrimental in this case, exacerbating a catastrophic immune response or alternatively masquerading the clinical progression of aspergillosis. Clinicians should be aware of immune reconstitution syndromes possibly leading to fatal outcomes in immunocompromised patients starting CCR-4 antagonists. Full article

Recurrent Pregnancy Loss (RPL) affects 1–2% of women, and its triggering factors are unclear. Several studies have shown that the vaginal, endometrial, and gut microbiota may play a role in RPL. A decrease in the quantity of Lactobacillus crispatus in local microbiota has been associated with an increase in local (vaginal and endometrial) inflammatory response and immune cell activation that leads to pregnancy loss. The inflammatory response may be triggered by gram-negative bacteria, lipopolysaccharides (LPS), viral infections, mycosis, or atypia (tumor growth). Bacterial structures and metabolites produced by microbiota could be involved in immune cell modulation and may be responsible for immune cell activation and molecular mimicry. Gut microbiota metabolic products may increase the amount of circulating pro-inflammatory lymphocytes, which, in turn, will migrate into vaginal or endometrial tissues. Local pro-inflammatory Th1 and Th17 subpopulations and a decrease in local Treg and tolerogenic NK cells are accountable for the increase in pregnancy loss. Local microbiota may modulate the local inflammatory response, increasing pregnancy success. Analyzing local and gut microbiota may be necessary to characterize some RPL patients. Although oral supplementation of probiotics has not been shown to modify vaginal or endometrial microbiota, the metabolites produced by it may benefit patients. Lactobacillus crispatus transplantation into the vagina may enhance the required immune tolerogenic response to achieve a normal pregnancy. The effect of hormone stimulation and progesterone to maintain early pregnancy on microbiota has not been adequately studied, and more research is needed in this area. Well-designed clinical trials are required to ascertain the benefit of microbiota modulation in RPL. Full article