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BMC Psychol. 2024 Aug 28;12(1):457. doi: 10.1186/s40359-024-01901-8.

ABSTRACT

BACKGROUND: Chronic kidney disease (CKD) is the third most common cause of death after cancer and heart disease. The continuous treatment of children with CKD was greatly challenged during the COVID-19 pandemic, which significantly impacted the CKD children’s prognosis and the caregivers’ psychological status. However, the influence mechanism of socioeconomic status, medical delay duration, traffic pressure, and online consultation duration on caregivers’ hope and psychological resilience still lacks relevant evidence.

METHODS: This study investigated the general social information, hope, and psychological resilience of 247 caregivers with CKD in 13 provinces of China in March 2020. Factor analysis and an exploratory Structural Equation Model ( SEM ) were used to find the best-fit model, and Bootstrapping was used to calculate the 95% CI of indirect effects.

RESULTS: The factor analysis obtained four common factors, namely, socioeconomic status (annual family income, education, and career stability), medical accessibility (online consultation duration, medical delay duration, and traffic pressure), hope (positive attitude, positive action, and intimate relationship) and psychological resilience (optimism, tenacity, and strength), with the cumulative contribution rate of 65.34%. Bootstrapping obtains the socioeconomic status β = 0.30 (95% CI [0.14, 0.47], P = 0.002), medical accessibility β = 0.31 (95% CI [0.12, 0.47], P = 0.002), and hope β = 0.40 (95% CI [0.27, 0.52], P = 0.002) has a direct impact on psychological resilience of CKD children caregivers, followed by medical accessibility β = 0.20 (95% CI [0.10, 0.38], P = 0.001) and hope β = 0.23 (95% CI [0.16, 0.32], P = 0.001) plays a mediating role between socioeconomic status and psychological resilience. The indirect impact effect β = 0.35 (95% CI [0.25, 0.50], P = 0.001) is greater than the direct impact effect β = 0.30 (95% CI [0.14, 0.47], P = 0.002).

CONCLUSIONS: Sufficient attention should still be given to children with immunodeficiency after the COVID-19 pandemic, such as CKD, to avoid infection of deadly. Secondly, the government should vigorously develop Primary medical institutions to ensure efficient treatment of severe patients in tertiary hospitals; Finally, the professional literacy of medical workers in remote diagnosis and treatment should be improved to enhance the country’s emergency response capacity for similar major public events and the requirements for normalised epidemic prevention and control.

PMID:39198911 | DOI:10.1186/s40359-024-01901-8

Rev Inst Med Trop Sao Paulo. 2024 Aug 26;66:e50. doi: 10.1590/S1678-9946202466050. eCollection 2024.

ABSTRACT

Yellow fever vaccine (YFV) is a live attenuated vaccine that can cause a mild infection in immunocompetent patients. However, it may not be self-limiting in patients with inborn errors of immunity (IEI) and may be the first and most severe presentation in these patients. A 10-month-old female infant sought emergency care presenting fever for three days and diffuse exanthema. She was a previous healthy child of consanguineous parents. The child had received YFV 28 days before the onset of symptoms. Upon hospital admission, petechial rash on the limbs and hepatosplenomegaly were noted on physical exam. Laboratory tests showed thrombocytopenia, increased serum aminotransferases and elevated gamma-glutamyl transferase (GGT) and alkaline phosphatase levels. During hospitalization she developed hypoactivity, drowsiness, and hypotonia. The possibility of viscerotropic and neurotropic vaccine associated disease was suspected and a possible primary immunodeficiency disease considered. The patient was tested for antibodies against the yellow fever virus (MAC ELISA) on serum and cerebrospinal fluid (CSF) samples, showing positive IgM results. Immunophenotyping showed low levels of lymphocytes and absence of T-cell receptor excision circles (TREC), leading to diagnose of severe combined immunodeficiency disease (SCID). Despite treatment, after 35 days of hospitalization, she evolved to cardiorespiratory arrest and death. Serious adverse events after administration of the YFV are rare and associated with neurological or visceral involvement in most cases. The unfavorable outcome highlights the importance of neonatal screening for SCID and the clinical suspicion of primary immunodeficiencies in infants who have serious adverse events to live virus vaccines.

PMID:39194142 | DOI:10.1590/S1678-9946202466050

Int J Pharm. 2024 Aug 24:124639. doi: 10.1016/j.ijpharm.2024.124639. Online ahead of print.

ABSTRACT

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that lacks expression of estrogen, progesterone, and HER2 receptor targets for therapy. Polymeric nanoparticles help address the challenges in treating TNBC by enabling tailored and targeted drug delivery. Biocompatible polymeric nanoparticles leverage enhanced tumor permeability for site-specific accumulation and ligand-mediated active targeting to boost specificity. Controlled, sustained intratumorally release of encapsulated chemotherapies, such as paclitaxel and curcumin, improves antitumor efficacy as demonstrated through preclinical TNBC models. However, the practical application of these nanomedicines still has room for improvement. Advancing personalized nanoparticle platforms that align treatments to TNBC’s expanding molecular subtypes shows promise. Expanding the polymer range through novel copolymers or drug conjugates may improve tumor penetration, stability, and drug encapsulation. Incorporating gene therapies, imaging agents, or triggering stimuli responsiveness into polymeric nanoparticles can also overcome innate and acquired drug resistance in TNBC while monitoring outcomes. This article reviews the different types of nanoparticles used to treat TNBC and the different mechanisms of nanoparticles that can deliver drugs to tumor cells. Collaboration across different disciplines aimed at developing combination therapies, immuno-oncology, tumor-targeting ligands, and translating preclinical safety/efficacy via scalable manufacturing practices is essential. Well-designed polymeric nanoparticles offer immense potential for patient-centric TNBC treatment, but continued optimization across bench to bedside efforts is critical for clinical realization and transforming patient outcomes.

PMID:39187034 | DOI:10.1016/j.ijpharm.2024.124639

Rinsho Shinkeigaku. 2024 Aug 24. doi: 10.5692/clinicalneurol.cn-001980. Online ahead of print.

ABSTRACT

Here we present the case of a 23-year-old female with a history of onychomycosis and oral thrush since childhood. She presented with a gradual onset of headache, and cerebrospinal fluid (CSF) analysis on admission revealed an elevated mononuclear cell count. Hydrocephalus was observed on brain MRI. Candida albicans (C. albicans) was detected in the CSF, and antifungal treatment was initiated to diagnose of Candida meningitis. Due to an insufficient therapeutic response, intraventricular administration of liposomal amphotericin B initiated; however, the lesions persisted. Subsequently, the patient experienced repeated occlusions of the ventriculoperitoneal shunt tube, ultimately dying from a bacterial shunt infection. Autopsy findings revealed diffuse fungal proliferation on the surface of the brainstem and ventricular walls. Genetic testing confirmed a diagnosis of CARD9 deficiency. Although CARD9 deficiency is a rare disease, genetic testing should be considered when primary immunodeficiency is suspected.

PMID:39183049 | DOI:10.5692/clinicalneurol.cn-001980

Cureus. 2024 Jul 26;16(7):e65434. doi: 10.7759/cureus.65434. eCollection 2024 Jul.

ABSTRACT

Homozygous mutations in the lipopolysaccharide-responsive vesicle trafficking, beach- and anchor-containing (LRBA) gene lead to a syndrome characterized by early-onset hypogammaglobulinemia, autoimmunity, lymphoproliferation, and inflammatory bowel disease. This report describes a 10-year-old female who experienced three seizure episodes, including two generalized tonic-clonic seizures (GTCS) and one focal seizure, alongside septic shock. The patient had a history of recurrent respiratory tract infections, inflammatory bowel disease, multiple blood transfusions, lymphadenopathy, significant organomegaly, and hematological abnormalities, all consistent with an LRBA deficiency. This case highlights the critical need for prompt recognition and identification of LRBA gene mutations to enable timely management and improve patient outcomes.

PMID:39184709 | PMC:PMC11344606 | DOI:10.7759/cureus.65434

Am J Rhinol Allergy. 2024 Aug 25:19458924241272990. doi: 10.1177/19458924241272990. Online ahead of print.

ABSTRACT

OBJECTIVES: Studies suggest that transplant patients are at a higher risk of developing chronic rhinosinusitis (CRS). However, there is a dearth of studies describing the factors that may be linked to the development of CRS in this population. Our objective is to identify the risk factors associated with the development of CRS in transplant recipients.

STUDY DESIGN: Retrospective cohort.

SETTING: Tertiary care center.

METHODS: This cohort included 3347 transplant recipients seen between 2017 and 2022. Of these, 2128 patients met the inclusion criteria and were grouped according to whether they were diagnosed with CRS during the post-transplant period. The analysis included both univariate and multivariate analysis to ascertain the odds ratio (OR) and predictive factors.

RESULTS: Of the 2128 patients, 649/2128 (30.4%) had CRS. CRS patients had an increased prevalence of previous endoscopic sinus surgery, allergic rhinitis, and recurrent acute rhinosinusitis in the pre-transplant period compared to the non-CRS group. According to the multivariate analysis, patients with primary immunodeficiency and additional transplant were 1.9 and 3.1 times more likely to develop CRS during the posttransplant period (95% CI: 1.3-2.6, p < .0001), (95% CI: 1.3 -7.3, p = .01), respectively. Sirolimus use was also associated with the development of CRS (OR = 1.4, 95% CI: 1.1-1.9, p = .01).

CONCLUSION: This study is the largest cohort aimed at determining the predictive factors associated with the development of CRS. Patients with pretransplant rhinologic conditions, hematologic deficiencies, and the utilization of specific immunosuppressants were found to have a higher likelihood of developing CRS following transplantation.

PMID:39183515 | DOI:10.1177/19458924241272990

Clin Lymphoma Myeloma Leuk. 2024 Jul 19:S2152-2650(24)00264-7. doi: 10.1016/j.clml.2024.07.008. Online ahead of print.

ABSTRACT

BACKGROUND: Immunoparesis, defined as suppression of uninvolved polyclonal immunoglobulins, occurs in up to 80% of patients with newly diagnosed multiple myeloma (NDMM). Infections are the second most common cause of mortality in this population, yet evidence regarding prognostic impact of immunoparesis in NDMM remains unclear.

MATERIALS AND METHODS: Using a prepublished protocol (CRD42022308687), we searched seven bibliographic databases from inception to February 2023 for studies reporting the impact of immunoparesis on clinical outcomes among adults with NDMM. The primary outcome of interest was overall survival (OS) and secondary outcomes were progression free survival (PFS) and infection risk. Effect sizes were quantified in terms of hazards ratio (HR) and pooled across studies using a random effects restricted maximum likelihood method. Heterogeneity was assessed using Cochran Q and the I² statistic. Publication bias was assessed using contour enhanced funnel plots.

RESULTS: Of 5175 studies screened, 7 studies involving 6091 patients met our search criteria. Immunoparesis was not associated with worse OS (pooled hazard ratio 1.30; 95% CI, 0.91-1.84; P-value .11), with significant heterogeneity among the studies (I2 = 72.9%; Cochran’s Q P-value .003). However, immunoparesis was associated with a significantly worse PFS (pooled hazard ratio 1.42; 95% CI 1.11-1.82; p value 0.013), with moderate heterogeneity (I2 statistic = 51%; Cochran’s Q P-value .056). Infection rates were not uniformly reported precluding meta-analysis. Visual examination of funnel plot revealed the possibility of publication bias.

CONCLUSION: Overall, our findings suggest that immunoparesis did not have a detrimental impact on OS, but was associated with a significantly shorter PFS. Further studies are needed to understand the complexity of immune system perturbations in NDMM.

PMID:39179448 | DOI:10.1016/j.clml.2024.07.008

Int J Biol Macromol. 2024 Aug 21:134959. doi: 10.1016/j.ijbiomac.2024.134959. Online ahead of print.

ABSTRACT

Codonopsis pilosula, an important medicinal and edible plant in traditional Chinese medicine, is used widely as a tonifying herb for various immunodeficiency diseases. A neutral polysaccharide (CPPs-D1N1) was purified from C. pilosula, composed of fructose and glucose in a molar ratio of 97.28:2.72, with an average molecular weight of 5.985 kDa. Structural analysis revealed a backbone composed of →1)-β-D-Fruf-(2 → units with some β-D-Fruf-(2 → linkages. In a murine immunosuppression model induced by cyclophosphamide injection, oral treatment with C. pilosula polysaccharide was administered, investigating changes in gut microbiota during therapy. The polysaccharide modulated serum immunoglobulins (Ig-G, Ig-M), cytokines (IL-2, IL-6, TNFα), and spleen and thymus indices in immunodeficient mice. Additionally, functional gene primer sequencing enrichment methods revealed alterations in abundance, diversity, and structure of butyrate-producing bacterial populations in the gut, with primary differential genera identified as Butyribacter, Rumanococcus, Dysosmobacter, and Ruseburia. This study provides in vivo evidence supporting the beneficial effects of C. pilosula polysaccharide oral therapy in improving gut microbiota, particularly butyrate-producing bacteria, during treatment of immunosuppressive diseases.

PMID:39179083 | DOI:10.1016/j.ijbiomac.2024.134959

Sci Adv. 2024 Aug 23;10(34):eadr0036. doi: 10.1126/sciadv.adr0036. Epub 2024 Aug 23.

ABSTRACT

CDCA7, encoding a protein with a carboxyl-terminal cysteine-rich domain (CRD), is mutated in immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome, a disease related to hypomethylation of juxtacentromeric satellite DNA. How CDCA7 directs DNA methylation to juxtacentromeric regions is unknown. Here, we show that the CDCA7 CRD adopts a unique zinc-binding structure that recognizes a CpG dyad in a non-B DNA formed by two sequence motifs. CDCA7, but not ICF mutants, preferentially binds the non-B DNA with strand-specific CpG hemi-methylation. The unmethylated sequence motif is highly enriched at centromeres of human chromosomes, whereas the methylated motif is distributed throughout the genome. At S phase, CDCA7, but not ICF mutants, is concentrated in constitutive heterochromatin foci, and the formation of such foci can be inhibited by exogenous hemi-methylated non-B DNA bound by the CRD. Binding of the non-B DNA formed in juxtacentromeric regions during DNA replication provides a mechanism by which CDCA7 controls the specificity of DNA methylation.

PMID:39178265 | DOI:10.1126/sciadv.adr0036

Arch Argent Pediatr. 2024 Aug 29:e202410370. doi: 10.5546/aap.2024-10370.eng. Online ahead of print.

ABSTRACT

Childhood-onset systemic lupus erythematosus (cSLE) is a multisystem disease; its severity depends on the organs involved. Monogenic diseases have been described as predisposing to the onset of cSLE. Analytical and immunological tests are used for diagnostic confirmation. The main goal of treatment is remission and flare prevention. Here we describe the clinical case of a patient with prolonged febrile syndrome, arthralgias, and anemia, positive analytical tests for antinuclear antibodies and anti-DNA antibodies and low values of complement C3, C4, and C1q; so the patient was diagnosed with cSLE associated with C1q deficiency. Patients with C1q deficiency present with early onset of disease and significant target organ damage with nephritis. An early diagnosis of cSLE is important to ensure an early and appropriate treatment. Treatment may be personalized depending on the underlying defect that generates the subtype of lupus.

PMID:39178162 | DOI:10.5546/aap.2024-10370.eng