Medical sciences (Basel, Switzerland)最新文献

Chronic Obstructive Pulmonary Disease (COPD) is a disease characterized by local and systemic inflammation independently of the risk factor; during the exacerbations, such inflammation is accentuated and amplified. A practical inflammatory marker and one with an applicable predictive value in the follow-up has been sought. FeNO has shown an excellent performance in that respect within the context of asthma and has also been studied in tobacco-smoke COPD (COPD-TS). In Biomass-smoke COPD (COPD-BS), this, to our knowledge, has not been evaluated.

Objective: To measure FeNO levels in patients with COPD-BS and to compare these with those of patients with stable COPD-TS and in healthy controls.

Methods: Transversal, observational, descriptive, comparative, and analytical study. A total of 57 patients, including 23 with COPD-BS, 17 with COPD-TS, and 17 healthy control subjects. The measurement of FeNO was carried out on all of these by means of the on-line chemiluminescence technique; the values were expressed in parts per billion (ppb) for their analysis.

Results: It was observed that the FeNO values were similar between COPD-BS and COPD-TS and were significantly different between the healthy and stable COPD (both groups). No correlation was found between pulmonary function and symptoms with FeNO in any of the groups.

Conclusions: The level of FeNO in stable COPD is found to be increased in a similar manner in COPD-BS and COPD-TS, with a significant difference on comparing it with that of the healthy subjects.

Background: Cardiovascular diseases (CVD) are a leading cause of mortality worldwide, influenced by genetic, environmental, and behavioral factors. This study examines the relationship between heavy metal exposure, chronic physiological stress (allostatic load), and lipid profiles, which are markers of CVD risk, using data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018.

Methods: We utilized structural equation modeling (SEM) to explore the associations between blood levels of lead, cadmium, allostatic load (AL), and lipid measures (low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides). The AL index was derived from cardiovascular, inflammatory, and metabolic biomarkers and categorized into quartiles to identify high-risk individuals, with an index out of 10 subsequently developed.

Results: The SEM analysis revealed that both heavy metal exposure and allostatic load are significantly associated with lipid profiles. Higher levels of lead and cadmium were associated with increased LDL and triglycerides, while higher AL scores were linked to increased LDL and triglycerides and decreased HDL levels. Age was also a significant factor, showing positive correlations with LDL and triglycerides, and a negative correlation with HDL.

Conclusions: This study underscores the multifactorial nature of CVD, highlighting the combined impact of environmental pollutants and physiological stress on lipid dysregulation. These findings suggest the need for integrated public health strategies that address both environmental exposures and chronic stress to mitigate cardiovascular risk. Further research is warranted to explore the underlying mechanisms and develop targeted interventions.

Introduction/aim: Central sensitivity to thyroid hormones refers to the responsiveness of the hypothalamic-pituitary-thyroid (HPT) axis to changes in circulating free thyroxine (fT4). Although dose-response relationships between thyroid hormones per se and urinary iodine (UI) levels have been observed, central sensitivity to thyroid hormones in relation to UI remains unexplored. The aim of the present study was to evaluate central sensitivity to thyroid hormones (by means of the Thyroid Feedback Quantile-based Index [TFQI], which is a calculated measure, based on TSH and fT4, that estimates central sensitivity to thyroid hormones) in pregnancy and to assess whether it differs according to gestational age and/or iodine intake.

Materials and methods: One thousand, one hundred and two blood and urine samples were collected from pregnant women (with a mean age ± SD of 30.4 ± 4.6 years) during singleton pregnancies; women with known/diagnosed thyroid disease were excluded. Specifically, TSH and fT4, anti-thyroid peroxidase antibodies and UI were measured in each trimester and at two months postpartum, while the TFQI was calculated for all the study samples. After the elimination of outliers, statistical analysis was conducted with analysis of variance (ANOVA) for the variables versus time period, while Pearson's correlation was used to assess the TFQI versus UI.

Results: The mean TFQI index ranged from -0.060 (second trimester) to -0.053 (two months postpartum), while the corresponding UI was 137 and 165 μg/L, respectively. The TFQI-UI correlation was marginally negative (Pearson r: -0.323, p: 0.04) and significantly positive (r: +0.368, p: 0.050) for UI values over 250 μg/L, in the first and the second trimesters of pregnancy, respectively.

Discussion: The TFQI is a new index reflecting central sensitivity to thyroid hormones. A lower TFQI indicates higher sensitivity to thyroid hormones. In our sample, the TFQI was mainly positively related to iodine intake in the second trimester of pregnancy (following the critical period of organogenesis). Thus, the observed changes in the TFQI may reflect the different ways of the central action of thyroid hormones, according to the phase of pregnancy. These results have the potential to enhance our comprehension of the changes in the HPT axis' function via variations in central sensitivity to thyroid hormones and its interplay with nutritional iodine status during pregnancy.

Osteoporosis, a skeletal disorder, is expected to affect 60% of women aged over 50 years. Dual-energy X-ray absorptiometry (DXA) scans, the current gold standard, are typically used post-fracture, highlighting the need for early detection tools. Panoramic radiographs (PRs), common in annual dental evaluations, have been explored for osteoporosis detection using deep learning, but methodological flaws have cast doubt on otherwise optimistic results. This study aims to develop a robust artificial intelligence (AI) application for accurate osteoporosis identification in PRs, contributing to early and reliable diagnostics. A total of 250 PRs from three groups (A: osteoporosis group, B: non-osteoporosis group matching A in age and gender, C: non-osteoporosis group differing from A in age and gender) were cropped to the mental foramen region. A pretrained convolutional neural network (CNN) classifier was used for training, testing, and validation with a random split of the dataset into subsets (A vs. B, A vs. C). Detection accuracy and area under the curve (AUC) were calculated. The method achieved an F1 score of 0.74 and an AUC of 0.8401 (A vs. B). For young patients (A vs. C), it performed with 98% accuracy and an AUC of 0.9812. This study presents a proof-of-concept algorithm, demonstrating the potential of deep learning to identify osteoporosis in dental radiographs. It also highlights the importance of methodological rigor, as not all optimistic results are credible.

The treatment landscape for metastatic renal cell carcinoma (RCC) has advanced significantly with first-line immunotargeted therapy combinations. However, no statistically significant differences were observed in the cohort of patients with favorable risk and some oncologists continue to use sunitinib in these patients. PD-L1 expression has emerged as a negative prognostic factor in RCC, particularly in sunitinib-treated patients, where higher PD-L1 levels are linked to worse outcomes. This article discusses the potential risks associated with the use of sunitinib in PD-L1-positive patients.

Introduction: Colorectal cancer (CRC) is the third most common cancer globally and a leading cause of cancer-related deaths. While liver metastasis is common, brain metastasis (BM) is rare, occurring in 0.1% to 14% of cases. Risk factors for BM include lung metastasis at diagnosis, rectal cancer, and mutations in RAS and KRAS genes. Due to its rarity, guidelines for BM screening and treatment are limited. The aim of this study is to identify the clinical characteristics and predictors of BM at the time of the initial diagnosis of CRC.

Methods: We evaluated patients ≥18 years old with metastatic colorectal cancer and brain metastases at diagnosis from the SEER database (2010-2021). A retrospective cohort study was conducted to analyze overall survival and predictive factors for brain metastasis, utilizing multivariate logistic regression, Kaplan-Meier survival analysis, and the Cox proportional hazards models, with p-values < 0.05 considered significant.

Results: Out of 24,703 patients with metastatic colorectal cancer (mCRC), 228 (0.92%) had brain metastasis (BM) at diagnosis. BM was more prevalent in average-onset mCRC (≥50 years) compared to early-onset (<50 years) (1% vs. 0.55%, p = 0.004). Certain factors, such as older age and adenocarcinoma subtype, were associated with BM. Additionally, Asians/Pacific-Islanders (HR 1.83 CI: 1.01-3-33, p = 0.045) and American Indians/Alaska Natives (HR 4.79 CI 1.15-19.97, p = 0.032) had higher mortality rates, while surgical treatment and chemotherapy were linked to decreased mortality. Patients with BM had significantly worse overall survival (6 months vs. 21 months, p < 0.001).

Conclusion: BM in mCRC is uncommon, but it is associated with significantly worse outcomes, including markedly reduced overall survival. Our study highlights several critical factors associated with the presence of BM, such as older age and specific racial/ethnic groups, which may inform risk stratification and early-detection strategies. Our findings emphasize the need for heightened awareness and screening for BM in high-risk mCRC patients, as well as the inclusion of these patients in clinical trials to explore tailored therapeutic approaches aimed at improving survival and quality of life.

Background: The aims of this study were to assess the perioperative morbidity, mortality and long-term survival of octogenarians undergoing acute type A aortic dissection repair (ATAAD), and to compare open and closed distal anastomosis techniques.

Methods: This was a single-centre retrospective study (2007-2021). Open versus closed distal anastomosis were compared. Uni- and multivariable logistic regression analyses were performed to identify independent predictors of in-hospital mortality. Kaplan-Meier and Cox proportional hazards methods were used to compare long-term survival.

Results: Fifty octogenarian patients were included (median age-82 years; closed distal-22; open distal-28). Median cardiopulmonary bypass time was 187 min (open distal vs. closed distal group; 219 min vs. 115.5 min, p < 0.01, respectively). Median cross-clamp time was 93 min (IQR; 76-130 min). Median circulatory arrest time was 26 min (IQR; 20-39 min) in the open-distal group. In-hospital mortality was 18% (open distal; 14.2% vs. closed distal; 22.7%, p = 0.44). Stroke was 26% (open distal; 28.6% vs. closed distal; 22.7%, p = 0.64). Median survival was 7.2 years (IQR; 4.5-11.6 years). Survival was comparable between open and closed distal groups (median 10.6 vs. 7.2 years, p = 0.35, respectively). Critical preoperative status (HR; 3.2, p = 0.03) and composite endpoint (renal replacement therapy, new neurological event, length of stay > 30 days or return to theatre; HR; 4.1, p = 0.02) predicted adverse survival. Open distal anastomosis did no impact survival.

Conclusions: ATAAD repair in selected octogenarians has acceptable short- and long-term survival. There is no significant difference between open versus closed distal anastomosis strategies.

This study evaluates the long-term outcomes of minimally invasive mitral valve repair (MIMVR) in patients with degenerative mitral regurgitation, focusing on survival, mitral valve repair failure, and re-operation rates. A cohort of patients undergoing three primary repair techniques-quadrangular resection, edge-to-edge repair, and artificial chordae implantation-was analyzed using time-to-event methods. The overall survival rates at 1, 10, and 20 years were high and comparable among the techniques, indicating effective long-term benefits of MIMVR. However, freedom from recurrence of moderate mitral regurgitation (MR) ≥ 2 was significantly higher in the quadrangular resection and edge-to-edge groups compared to the artificial chordae group. No significant differences were observed for recurrent MR ≥ 3. Re-operation rates were low and similar across all techniques, underscoring the durability of MIMVR. Pre-discharge residual MR ≥ 2 was identified as a strong predictor of long-term repair failure. These findings confirm the effectiveness of MIMVR, with all techniques demonstrating excellent long-term survival and durability.

This research aims to determine whether HLA heterozygosity confers a protective effect against hepatitis B virus infection by analyzing the relationship between HLA diversity and the risk of hepatitis B virus (HBV) infection. A total of 327 hepatitis B patients were selected and categorized based on their clinical status: 284 patients with chronic HBV infection and 43 patients with HBV-related liver cirrhosis (LC). The control group included 304 healthy individuals. HLA genotyping for 11 loci, including HLA class I and class II, was conducted using next-generation sequencing. The results of this study indicate a statistically significant negative correlation between HLA class II heterozygosity and the risk of HBV infection. Specifically, heterozygosity in HLA-DQB1 (OR = 0.49, 95% CI = 0.31-0.76, p = 0.01277) and HLA-DRB1 (OR = 0.42, 95% CI = 0.24-0.77, p = 0.01855) were significantly associated with protection. Subgroup analysis was conducted to explore the effect of HLA diversity among pathological subtypes (chronic hepatitis B and control group, liver cirrhosis and control group). For liver cirrhosis, compared with the control group, a decreased risk of LC was possibly associated with the heterozygosity of HLA class I locus B (OR = 0.24, 95% CI = 0.09-0.65, p = 0.0591), but this hypothesis was not confirmed by other studies. The diversity of HLA, measured by HLA heterozygosity, was associated with a protective effect against HBV infection.

The rise in biological therapies has revolutionized oncology, with immunotherapy leading the charge through breakthroughs such as CAR-T cell therapy for melanoma and B-ALL. Modified bispecific antibodies and CAR-T cells are being developed to enhance their effectiveness further. However, CAR-T cell therapy currently relies on a costly ex vivo manufacturing process, necessitating alternative strategies to overcome this bottleneck. Targeted in vivo viral transduction offers a promising avenue but remains under-optimized. Additionally, novel approaches are emerging, such as in vivo vaccine boosting of CAR-T cells to strengthen the immune response against tumors, and dendritic cell-based vaccines are under investigation. Beyond CAR-T cells, mRNA therapeutics represent another promising avenue. Targeted delivery of DNA/RNA using lipid nanoparticles (LNPs) shows potential, as LNPs can be directed to T cells. Moreover, CRISPR editing has demonstrated the ability to precisely edit the genome, enhancing the effector function and persistence of synthetic T cells. Enveloped delivery vehicles packaging Cas9 directed to modified T cells offer a virus-free method for safe and effective molecule release. While this platform still relies on ex vivo transduction, using cells from healthy donors or induced pluripotent stem cells can reduce costs, simplify manufacturing, and expand treatment to patients with low-quality T cells. The use of allogeneic CAR-T cells in cancer has gained attraction for its potential to lower costs and broaden accessibility. This review emphasizes critical strategies for improving the selectivity and efficacy of immunotherapies, paving the way for a more targeted and successful fight against cancer.