Archives of Medical Research最新文献

Hereditary transthyretin cardiac amyloidosis (ATTRv-CA) after liver transplantation remains challenging to treat due to residual amyloid deposits in extrahepatic organs, including the heart. Tafamidis, a transthyretin tetramer stabilizer, has shown promise in the treatment of ATTRv-CA; however, its efficacy and safety after liver transplantation are uncertain. In this preliminary retrospective review, we assessed the efficacy and safety of tafamidis (80 mg) in three ATTRv-CA cases after liver transplantation. Following one year of treatment, all patients experienced improvement in dyspnea, New York Heart Association functional class, brain natriuretic peptide levels, and cardiac troponin T levels. No significant changes in echocardiographic parameters were observed. Notably, no cardiovascular or drug-related adverse events occurred during treatment. Our findings suggest that tafamidis may benefit post-liver transplant patients with ATTRv-CA and warrant further investigation through randomized controlled trials with larger cohorts. This study highlights a potential therapeutic avenue for the management of cardiovascular involvement in this challenging patient population.

Background

The Organization for Economic Cooperation and Development (OECD) member states are heterogeneous in their social, economic, and health conditions.

Aims

a) to analyze age-specific mortality rate (ASMR) and age-specific disability-adjusted life year (DALY) rate among older people in countries by age groups (65–74 years and 75+ years) and sex, and b) to estimate the association between age-specific DALY rate with Socio-Demographic Index (SDI) and with Healthcare Access and Quality Index (HAQI).

Methods

Secondary analysis of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. The ASMR and the age-specific DALY rate were reported for the years 1990, 2005, and 2019. Correlation between age-specific DALY rate with SDI and HAQI was estimated.

Results

There were differences in the level and change in ASMR and the age-specific DALY rates among OECD countries. Overall, men had a higher rate for both age groups in both indicators. Although the rates have been reduced between 1990 and 2019, some countries stand out for continuing to have higher rates than countries with better socioeconomic levels. The disease burden profile also differed between adults aged 65–74 years and those aged 75+ years. In almost all cases, there was a negative and statistically significant correlation between the age-specific DALY rate with SDI and HAQI.

Conclusions

The burden of mortality and DALY in OECD countries is convergent because they have decreased over time in all countries but diverge in the magnitude and speed of change.

Background

The SARS-CoV-2 pandemic challenged health systems worldwide. In Mexico, the Public Health Incident Management Command (COISS) strategy was implemented to improve health care for patients with COVID-19 who required hospitalization.

Aim

To evaluate the impact of the COISS strategy on case fatality rates (CFR) and years of life lost (YLL) in hospitalized patients with COVID-19.

Materials and Methods

The COISS strategy included eight actions implemented in states with high epidemic risk (COISS states). A secondary analysis of the public database from the Mexican Ministry of Health was performed considering patients with confirmed diagnoses of SARS-CoV-2 infection. The COISS strategy effectiveness was evaluated by its impact on in-hospital CFR and YLL at the beginning (T0) and end (T1) of the third wave, and at the end of the fourth wave (T2) and compared to states without intervention (non-COISS states).

Results

At T0, COISS states showed a higher CFR for hospitalized patients than non-COISS states, which decreased after the strategy implementation. After correction for baseline conditions, lower relative CFR at T1 and T2, compared to T0, and a protective effect in different age groups, especially in those ≥65 years, were found in hospitalized patients in COISS states. The COISS strategy was associated with lower CFR in hospitalized patients with COVID-19 at both T1 and T2. At T0, YLLs were higher in COISS states, but there were no significant differences at T1 and T2.

Conclusions

COISS interventions effectively reduced CFR in hospitalized patients with COVID-19, providing protection to vulnerable patients and reducing the YLL gap.

Osteoporosis (OP) is a chronic disease that affects older adults’ quality of life, with fragility fractures (FF) being its most significant consequence due to their impact on healthcare systems in terms of morbidity, and economic and caregiving burden. FF are defined as fractures resulting from low-energy trauma, defined as falls from a standing height or less, and are usually considered osteoporotic (1). World demographic projections warn of a significant increase in adults aged 65 and older by 2050. These demographic changes mean that OP and FF will soon become an even greater challenge for healthcare systems, where prevention programs should be a priority.

In Mexico, FF is also a public health challenge, with an initial reported incidence of nearly 2,000 cases per 100,000 population, and a projected seven-fold increase by 2050. Given this scenario, there is an urgent need for policy- and decision-makers to change their approach and formulate health policies that guarantee that people aged 65 and older are screened for fractures and have access to appropriate care. These policies should be part of a strategy to minimize FF and ensure active and healthy aging according to the WHO's Decade of Healthy Ageing.

In this context, a group of Mexican experts representing different health organizations interested in the burden of OP and FF met to discuss possible strategies to reduce their burden for the next decade and summarize them in this Call to Action to promote public policies that prioritize an evidence-based approach to the prevention and treatment of OP and FF.

Background

Patients with endometriosis tend to have a low body mass index, suggesting an inverse relationship between body fat and risk of disease. This is supported by evidence that miRNAs differentially expressed in endometriosis induce browning of pre-adipocytes in vitro. Thus, we hypothesize that endometriosis may underlie adipose tissue (AT) dysfunction and browning.

Aims

Identify inflammation and browning processes in AT collected from endometriosis patients.

Methods

Visceral and subcutaneous AT samples were obtained during endometriosis (n = 32) or uterine myoma (n = 14; controls) surgery. Blood catecholamines were determined by high-performance liquid chromatography while IL-6 and TGF-β levels were quantified by ELISA. Adipocyte cross-sectional areas were analyzed in H&E-stained sections by computer-assisted morphometry. Macrophages (F4/80; Galectin-3) and browning activation (UCP-1; PGC-1α) in tissues were identified by dual label immunofluorescence. Expression of inflammatory (IL-6; MCP-1; Galectin-3; CD206; TIMP1; TGF-β) and browning-related (UCP-1; PGC-1α; DIO2; CITED1; CIDEA; TMEM26; TBX1; PRDM16; PPAR-γ) molecules in AT were assessed by RT-PCR and Western blotting.

Results

Compared to controls, patients presented smaller adipocytes, especially in VAT, and lower norepinephrine levels. Serum IL-6, but not TGF-β, was increased in patients. UCP-1, PGC-1α, IL-6, and MCP-1 were upregulated in VAT from endometriosis women, which also evidenced a reduction of CD206, relative to controls. However, no differences were found in mRNA expression of IL-6, TIMP1, and TGF-β nor Galectin-3 protein levels. In SAT, protein expression remained unchanged between patients and controls.

Conclusions

Our findings support an endometriosis’ role as a pro-catabolic state along with local signals of VAT browning and inflammation.

Background

The prevalence of oral human papillomavirus (HPV) in the healthy population and patients with oral diseases such as oral squamous cell carcinoma (OSCC), oral potentially malignant disorders (OPMDs), and oral benign lesions (BL), is not consistently described in the literature, with scarce and often heterogeneous data. In addition, the efficacy of HPV prophylactic vaccines in preventing HPV-related oral disorders has been scarcely investigated.

Methods

The prevalence of HPV and the potential impact of vaccines were analyzed in 1,415 oral rinse specimens, collected over 10 years and grouped into four categories based on histological/clinical diagnosis.

Results

HPV prevalence in OSCC, OPMD, and BL patients and in healthy individuals potentially exposed to HPV (HPE) was comparable (12.7 vs. 27.2% vs. 13.5 vs. 9%). Statistical analysis of the vaccine impact involved calculating high and low estimates and showed a significant difference only for the low effect. The nonavalent vaccine had higher low estimates than the bivalent vaccine in OSCC and HPE patients (29.6 vs. 51.9%, p < 0.05; 18.2 vs. 42.4%, p < 0.05), while for OPMD and BL, the frequency of bivalent low estimates was lower than that of quadrivalent and nonavalent (48.6 vs. 68.6%, p < 0.05 and 48.6 vs. 77.1%, p < 0.05; 23.9 vs. 50.7%, p < 0.05, and 23.9 vs. 63.4%, p < 0.05).

Conclusions

This study provided new insights into the prevalence of oral HPV and showed that the nonavalent vaccine may provide better protection than the other vaccines in the presence of an OSCC diagnosis. Conversely, the quadrivalent vaccine may be sufficient to prevent OPMD and BL.

It is well known that oocytes are produced during fetal development and that the total number of primary follicles is determined at birth. In humans, there is a constant loss of follicles after birth until about two years of age. The number of follicles is preserved until the resumption of meiosis at puberty and there is no renewal of the oocytes; this dogma was maintained in the last century because there were no suitable techniques to detect and obtain stem cells. However, following stem cell markers, several scientists have detected them in developing and adult human ovarian tissues, especially in the ovarian surface epithelial cells. Furthermore, many authors using different methodological strategies have indicated this possibility. This evidence has led many scientists to explore this hypothesis; there is no definitive consensus to accept this idea. Interestingly, oocyte retrieval from mature ovaries and other tissue sources of stem cells has contributed to the development of strategies for the retrieval of mature oocytes, useful for assisted reproductive technology. Here, we review the evidence and controversies on oocyte neooogenesis in adult women; in addition, we agree with the idea that this process may occur in adulthood and that its alteration may be related to various pathologies in women, such as polycystic ovary syndrome, premature ovarian insufficiency, diminished ovarian reserve and several infertility and genetic disorders.

Background

Systemic sclerosis (SSc) is an autoimmune disease (AD), that receives less attention compared to rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and primary Sjögren's syndrome (pSS). This study aims to analyze transcriptional profiles and immune cell composition in peripheral blood mononuclear cells (PBMC) from SSc patients compared to other ADs.

Methods

RNA-seq data from 119 untreated patients (eight with SSc, 42 with RA, 41 with pSS, 28 with SLE) and 20 healthy controls were analyzed. Bioinformatics tools were employed to identify differentially expressed genes (DEGs), biological functions and immune cell profiles unique to SSc and shared with other ADs.

Results

1,148 DEGs were found in SSc, with upregulated genes associated with megakaryocyte processes and downregulated genes associated with neutrophil function and immune response.

DEGs, including ALDH1A1 and MEGF9, were associated with neutropenia. Upregulated transcription factors (TFs) were linked to embryonic hematopoiesis and downregulated TFs were involved in leukocyte differentiation and immune regulation. Comparative analysis with other ADs revealed common pathogenic pathways, emphasizing megakaryocyte proliferation. Neutrophils count was significantly decreased in ADs (p < 0.001) compared to healthy controls. Comparative analysis highlighted common pathways, particularly in megakaryocyte proliferation, and unique genes (MEGF9, MMP8, and KRT family members) in SSc, suggesting roles in neutrophil function, skin integrity, and fibrosis.

Conclusions

This study identifies dysregulated gene expression (KRT and MMP8) associated with neutrophil function and increased megakaryocytes in SSc, highlighting common patterns across autoimmune diseases. These findings offer new insights into the potential pathogenesis of SSc, and help to explore new targets for the treatment.