Carolina Sanchez Aranda

Sporotrichosis is an infection caused by fungi of the Sporothrix complex that can affect both humans and animals. In most cases, it is a benign infection limited to the skin and subcutaneous tissue, rarely disseminating to other organs with systemic involvement. Diagnosis is based on clinical data, epidemiological data, and laboratory tests, with culture being considered the gold standard. The disease generally has a good prognosis and is usually resolved with appropriate antifungal treatment. This case report describes an atypical presentation of sporotrichosis with suppurative nodules and orbital bone involvement in an adolescent followed at the pediatric infectious diseases outpatient clinic of our institution. The patient was followed longitudinally for 12 months due to a lesion on the left upper back with lymphocutaneous involvement, which progressed to osteomyelitis of the left orbit. Deep lesion culture identified Sporothrix spp. The sporotrichosis was considered disseminated, and treatment with oral itraconazole for 12 months was initiated. Complete remission of both cutaneous and bone lesions occurred after five months of treatment. The patient was discharged from outpatient follow-up after one year.

Chronic granulomatous disease (CGD) is an inborn error of immunity (IEI) caused by mutations in genes encoding components of the NADPH oxidase complex, leading to defective microbial killing and increased susceptibility to infections. This study analyzed clinical, genetic, and geospatial data from 238 CGD patients across eight Latin American countries. Genetic variants were identified in 141 patients (59%), with XL-CGD being the most common form (77%). Pneumonia (80%), lymphadenopathy (63%), and skin infections (55.5%) were frequent, with bacteria and fungi, such as Staphylococcus aureus, Aspergillus spp., and mycobacteria, as major pathogens. Antimicrobial prophylaxis was widely used, while IFN-γ was mainly prescribed in Mexico, mainly in cases of classic CGD (XL-CGD). Hematopoietic stem cell transplantation (HSCT) did not improve survival compared to prophylaxis. The leading cause of death was infection, particularly pneumonia and sepsis. XL-CGD patients had worse survival outcomes. The study highlights the need for improved genetic diagnosis, newborn screening, regional treatment guidelines, and expanded access to HSCT.

Age-related hearing loss (ARHL) is a common condition among older adults. It has long been established that ARHL is more prevalent, is more severe, and tends to occur earlier in men than in women. A key factor contributing to ARHL is oxidative stress, which harms the inner ear cells. Sirtuins are a family of proteins that play critical roles in cellular regulation, particularly in response to stress and aging, and have demonstrated anti-aging effects. Cocoa flavonoids, due to their antioxidant properties, have been reported to provide numerous health benefits. The present study aimed to evaluate the efficacy of cocoa in preventing oxidative damage in the cochlea of aging mice mediated by Sirtuins, as well as to determine possible differences between sexes. Female and male C57Bl/6 J mice were randomly assigned to two study groups: standard diet and cocoa-supplemented diet. At the ages of 6, 14, and 22 months, the animals were sacrificed, and cochleae were harvested to measure the expression of Sirtuins-1, -3, forkhead box O3 (FOXO3), p53, antioxidant enzymes, oxidative DNA damage, and levels of reactive oxidative species (ROS). Our results indicated that cocoa attenuated oxidative DNA damage, reduced ROS levels, and induced the expression of SIRT1, -3, FOXO3, and p53 in the cochlea of aged mice. Furthermore, the activity of antioxidant enzymes in aged mice was restored with the cocoa diet. Sex differences were observed in several of these variables. These results indicate that cocoa protects against oxidative damage through Sirtuins. In conclusion, cocoa may have therapeutic potential against ARHL. Graphical Abstract

Purpose: This study aimed to evaluate the immunological response to the 23-valent pneumococcal polysaccharide vaccine (PPV23) in patients investigated for immunodeficiencies due to recurrent infections at EPM-UNIFESP Clinical Immunology outpatient clinic. Methods: This is a longitudinal retrospective study. Data were collected from the medical records of patients between 2012 and 2020. The analyses were developed in two stages: before and after administration of the PPV23 vaccine. Results: A total of 390 patients who received the PPV23 vaccine were selected. Among those who demonstrated an adequate serological response (63.6%), there was a notable decrease in the risk of upper respiratory tract infections (URTI) by 66%, tonsillitis by 74%, otitis by 76%, sinusitis by 49%, and uncomplicated pneumonia (PNM) by 77%. For invasive infections, the risk reduction was 95% for pneumonia with parapneumonic effusion and 93% for meningitis. Conclusions: The study demonstrated a significant decrease in the risk of bacterial infections following the administration of the PPV23 vaccine in this population. Therefore, we recommend including PPV23 in the vaccination schedule following pneumococcal conjugated vaccines for patients with recurrent pneumococcal infections to enhance protection and avoid complications.

Recent studies on head and neck squamous cell carcinoma (HNSCC) tumorigenesis have revealed several dysregulated molecular pathways. The phosphatidylinositol-3-kinase (PI3K) signaling pathway is frequently activated in HNSCC, making it an attractive target for therapies. PHT-427 is a dual inhibitor of PI3K and the mammalian target of AKT/PDK1. This study evaluates the anticancer efficacy of the inhibitor PHT-427 loaded into polymeric nanoparticles (NP) based on α-TOS (NP-427) administered by intratumoral injection into a hypopharyngeal squamous cell carcinoma (FaDu cells) heterotopic xenograft mouse model. The nanocarrier system, based on block copolymers of N-vinylpyrrolidone (VP) and a methacrylic derivative of α-TOS (MTOS), was synthesized, and PHT-427 was loaded into the delivery system. First, we evaluated the effect of NP-427 on tumor growth by measuring tumor volume, mouse weight, survival, and the development of tumor ulceration and necrosis. In addition, we measured PI3KCA/AKT/PDK1 gene expression, PI3KCA/AKT/PDK1 protein levels, Epidermal Growth Factor Receptor (EGFR), and angiogenesis in the tumor tissue. PHT-427 encapsulation increased drug efficacy and safety, as demonstrated by decreased tumor volume, reduced PI3K/AKT/PDK1 pathway expression, and improved antitumor activity and necrosis induction in the mouse xenograft model. EGFR and angiogenesis marker (Factor VIII) expression were significantly lower in the NP-427 group compared to other experimental groups. Administration of encapsulated PHT-427 at the tumor sites proves promising for HNSCC therapy.

Selective IgM deficiency (SIgMD) has recently been included in the inborn errors of immunity classification. SIgMD has conflicting diagnostic criteria and diverse clinical and immunological findings. We aimed to assess the clinical and laboratory profiles of patients with SIgMD and to compare the data of patients diagnosed using two inclusion criteria. This was a descriptive, retrospective, observational, collaborative study. Patients were included according to the following definitions: Group 1, IgM levels < 0.20 g/L in children and < 0.30 g/L in adults, and Group 2, serum IgM levels below 2SD and, for both, absence of associated immunological diseases or secondary causes. The protocol was approved by the Ethics Committee, and patients provided consent. In total, 75 patients were included: 37 (16 M:21F; mean age, 52.92) and 38 (13 M:25F; mean age, 53.47) in Groups 1 and 2, respectively. The most frequent clinical manifestations were allergic rhinitis (G1, 45.9%; G2, 36.8%), asthma (G1, 37.8%; G2, 28.9%), and pulmonary infections (G1, 27.03%; G2, 21.05%). Chromosomopathies (16.22%) and neoplasia (13.51%) were more frequent in G1, whereas URTI (23.68%) and skin infections (23.68%) were more common in G2. There was no difference in sex or mean age at symptom onset between both groups of patients. Regarding the clinical picture, 90.7% of the lesions were benign (68/75). Chromosomopathies may be associated with SIgMD, suggesting the need to quantify serum IgM levels in these cases. Considering the possibility of developing autoimmunity, neoplasia, and common variable immunodeficiency, it is advisable to follow up patients with SIgMD.

Age-related hearing loss, or Presbycusis, is the most frequent sensory deficiency in older adults and is associated with comorbidities such as falls, cognitive decline, and frailty. Frailty is related to poor health outcomes in old age. Recent research suggested that age-related hearing loss may be a potentially modifiable risk factor for frailty, although inconclusive. The use of animal models to study the correlation between age-related hearing loss and frailty is important to test future interventions to be translated into clinical practice. The aim of this study was to determine if there is an association between age-related hearing loss and frailty in experimental animals based on the human frailty phenotype. This research studied male and female C57Bl/6J mice at different ages (6, 14, and 22 months). Auditory steady-state response threshold shifts were measured at different frequencies. To assess frailty status, we were based on the “Valence Score,” which consists of measuring: weakness, weight loss, low level of activity, slowness, and little resistance. We found that hearing is significantly lower in older age groups. The mice become frail as they age. The worsening in auditory steady-state responses threshold shifts with age correlates significantly with an increasing frailty. No significant differences were found between both sexes. Our research is, to our knowledge, the first carried out in experimental animals to establish the association between age-related hearing loss and frailty, which would provide a useful tool to evaluate future interventions in mice before translating them into clinical practice.