Annals of medicine最新文献

Background: Autonomic dysfunction, including orthostatic hypotension and postural tachycardia syndrome, has emerged as a COVID-19 complication. This nationwide propensity score-matched cohort study investigated COVID-19's impact on subsequent prescriptions of autonomic dysfunction in Japan.

Patients and methods: Using a claims database covering 16 million residents identified between 2020 and 2022, propensity-score matching (PSM) created comparable groups of COVID-19 patients and controls. PSM used age, sex, calendar month, comorbidities, and baseline medications, with nearest-neighbor 1:1 with replacement. The primary composite outcome was the first outpatient prescription of midodrine, fludrocortisone, amezinium methylsulfate, and droxidopa. Cox proportional hazards models yielded hazard ratios (HRs) with 95% confidence intervals (CIs). Effect modifications were examined by subgroups.

Results: Among 3,074,329 matched pairs, over a median follow-up of 8 months, 13011 composite outcome were observed, and COVID-19 infection was associated with a 36% relative increase in prescriptions (HR 1.36, 95%CI 1.32-1.41). The risk persisted beyond one year, with the strongest association observed for fludrocortisone (576 events, HR 1.71, 95%CI 1.44-2.02), although the frequency was the highest in midodrine prescription (7009 events, HR 1.28, 95%CI 1.22-1.34). Subgroup analysis revealed higher risks among older individuals, males, those with myocardial infarction, heart failure, and antihypertensive medications.

Conclusions: COVID-19 infection is significantly associated with increased initiation of pharmacotherapy for autonomic dysfunction, with sustained risk beyond one year. These findings highlight the to manage autonomic dysfunction among COVID-19 survivors and informing clinical care and public health planning.

Background: The maxillary sinus (MS) exhibits interindividual anatomical variation influenced by sex, age, and craniofacial morphology. Understanding these variations is essential for surgical, endodontic, and implant planning. However, morphometric data for Saudi subpopulations, particularly from northern regions such as Ha'il, remain limited.

Objective: To assess MS morphometric dimensions using cone-beam computed tomography (CBCT) in a Saudi subpopulation from the Ha'il region and to evaluate variations according to sex, age, and laterality.

Methods: A retrospective CBCT-based cross-sectional study analysed 1,018 scans of Saudi adults aged 18-70 years. Sinus width, length, area, and perimeter were measured bilaterally on standardised coronal sections. Statistical analyses included Mann-Whitney U, Wilcoxon signed-rank, Kruskal-Wallis, and repeated-measures ANCOVA tests, with significance set at p < 0.05.

Results: Males demonstrated significantly larger MS dimensions than females, particularly for area (p = 0.043), perimeter (p = 0.045), and width after covariate adjustment (p = 0.007). No significant age-related differences were observed across adult groups. Although right-left differences were statistically significant for all parameters (p < 0.01), the magnitude of asymmetry was minimal and clinically insignificant. Overall, MS dimensions remained stable throughout adulthood with a slight right-sided laterality predominance.

Conclusion: CBCT-based morphometric assessment of the MS in a Saudi subpopulation from the Ha'il region revealed significant sex-related differences, minimal laterality-related asymmetry, and stable dimensions across adult age groups. These region-specific normative data enhance anatomical understanding and support improved diagnostic accuracy and procedural safety in implantology, oral surgery, maxillofacial practice, and forensic applications.

Background: The testis is a male-specific organ that plays a central role in spermatogenesis and androgen secretion. Testicular ageing is a hallmark of male senescence. However, the underlying mechanisms, as well as strategies to prevent, delay, or reverse this process, remain incompletely understood.

Discussion: As a critical component of male ageing, testicular ageing has attracted broad scientific attention, with ongoing efforts to identify effective strategies to delay or prevent its onset, though therapeutic efficacy remains limited. In this review, we summarise the biological and clinical features of testicular ageing, discuss its underlying molecular and cellular mechanisms, and highlight emerging strategies aimed at mitigating age-related testicular dysfunction, with the goal of advancing understanding and improving therapeutic outcomes.

Conclusions: Testicular ageing is a defining feature of male senescence, marked by progressive structural deterioration and declining steroidogenic and spermatogenic capacity. Although lifestyle, pharmacological, and stem-cell-based interventions show promise, their clinical applicability remains limited. A deeper mechanistic understanding and well-designed, large-scale prospective studies are essential to establish effective strategies for delaying or preventing testicular ageing.

Background: Early spontaneous abortion (ESA) is recognized as the most common complication during pregnancy and is often linked to dysfunction in the trophoblast and placenta. Studies suggest that downregulation of trophoblast oestrogen-related receptor gamma (ESRRG) may play a significant role in the impairment of placental function. In light of these findings, we evaluated the impact of ESRRG on trophoblast and placental function in ESAs, aiming to uncover new targets for diagnosis and treatment.

Patients/materials and methods: Bioinformatics methods were used to analyse differentially expressed genes in the trophoblast of ESA patients and normal controls. ESA Patients and controls were recruited and the villus tissues were collected. Protein and mRNA levels were determined by western blot and qRT-PCR, respectively. Mitochondrial morphological changes in trophoblasts were observed via transmission electron microscopy. CCK8 and Transwell assays were conducted with ESRRG-knockdown HTR-8/SVneo cells. MitoSOX staining, JC-1 assays and ATP quantification were used to assess mitochondrial function in vitro. In addition, Esrrg was overexpressed in ICR female mice, and the number of embryos in the uterus was determined.

Results: The expression of ESRRG was significantly decreased in the placental villous tissue of ESA patients, accompanied by abnormal mitochondrial morphology and decreased ATP levels in trophoblast cells. Impaired proliferation, invasion, migration and tube formation abilities were observed in ESRRG-downregulated HTR-8/SVneo cells, as well as impaired mitochondrial function. ESRRG overexpression was associated with improved trophoblast functionality in a lipopolysaccharide-induced abortion model in ICR mice, leading to an increased number of retained embryos in the uterus.

Conclusion: In summary, this study revealed that ESRRG downregulation plays an important role in ESA, providing new targets for diagnosis and treatment.

Background: Many patients with hypertensive nephropathy progress to chronic kidney disease (CKD). Targeting the core pathophysiological pathway of endothelin-1 activation, this study aimed to elucidate response patterns to the endothelin receptor type A/B (ETA/ETB) antagonist bosentan and construct a personalized prediction model.

Methods: This single-centre retrospective cohort study enrolled 166 patients with hypertension-related nephropathy confirmed by renal biopsy. Risk stratification was performed based on a pathological injury scoring. Three efficacy trajectories were identified using latent variable growth mixture models. Efficacy drivers were screened via random forest algorithms. Finally, early response thresholds were established using receiver operating characteristic (ROC) curves.

Results: Patients in the high-damage group exhibited significantly lower creatinine reduction than those in the low-damage group. Trajectory analysis revealed three patterns: sustained improvement (65.1%), with a 12-month creatinine reduction of 110.8 μmol/L, and deterioration (12.0%), with a deterioration inflection point at 5.3 ± 1.7 months and a subsequent creatinine increase of 40.2 μmol/L. Pathological injury score was the primary determinant of efficacy and was significantly negatively correlated with creatinine reduction (r = -0.61). Early response threshold analysis indicated that ΔCr_3M ≥ 42.3 μmol/L predicted 12-month efficacy, with an area under the curve (AUC) of 0.79. The early target-achievement group demonstrated significantly greater creatinine reduction than the nonachievement group. Compared with the non-sodium-glucose cotransporter-2 inhibitor (SGLT2i) group, the SGLT2i group demonstrated a 59% reduction in creatinine, while the diabetic subgroup showed a 47.1% smaller reduction than the nondiabetic subgroup.

Conclusions: Bosentan may improve glomerular haemodynamics in patients with hypertensive nephropathy. We propose pathological and early-response thresholds that could guide dynamic, precision interventions before critical inflection points, potentially paving the way for an upgrade from static to proactive management. These findings require validation in larger cohorts.

Objective: To explore the clinical significance of new haematological indicators, including rheumatoid arthritis-specific citrullinated protein (RA-CP), haemoglobin-to-red cell distribution width ratio (HRR), and mean platelet volume/platelet count (MPV/PC) ratio, in rheumatoid arthritis (RA). This study is the first to evaluate the combined diagnostic utility of RA-CP and HRR in RA.

Methods: Data from 700 subjects, including RA patients, patients with other autoimmune diseases, and healthy controls, were retrospectively analyzed. The relationships between these indicators and the risk of RA were assessed using logistic regression, correlation, and receiver operating characteristic (ROC) curve analyses.

Results: There were significant differences in RA-CP, HRR, and MPV/PC among the three groups (p < 0.001, for all). Logistic regression analysis indicated RA-CP and HRR as independent predictors of RA (p < 0.001, for both). Moreover, RA-CP and HRR were closely associated with the clinical characteristics. In addition, ROC curve analysis revealed that the combined detection of RA-CP, HRR, and anti CCP antibody achieved the highest area under the ROC curve (AUC_{RA - CP + HRR + antiCCP antibody} = 0.998) for the diagnosis of RA and also improved the diagnostic sensitivity (98.31%).

Conclusion: RA-CP and HRR were identified as independent predictors of RA, including RA-CP as a risk factor for RA and HRR as a protective factor for RA. Combined detection of RA-CP, HRR, and anti-CCP antibody could enhance the accuracy and sensitivity of laboratory diagnosis. Although MPV/PC did not demonstrate significant independent predictive value in this study, this represents the first exploration of its potential clinical role in RA.

Background: Tuberculosis infection (TBI) is a significant cause of bronchiectasis (BE). Identifying risk factors for radiological BE (RBE) could enhance the early detection of high-risk individuals following TB infection. This study aimed to develop and validate a novel Inflammation-Nutrition Risk Score (INRS) and a corresponding nomogram model to predict the risk of RBE after TBI.

Patients and methods: We enrolled 2,210 post-TBI patients from two medical centres. Data from 1,825 patients at Wuhan Jinyintan Hospital were used to develop the INRS and the RBE nomogram. An independent cohort of 385 patients from Wuhan Union Hospital served as an external validation set.

Results: The INRS was derived from four parameters: PNI, HALP score, Lg(SII) and CAR. Multivariate analysis identified the following independent risk factors for RBE: age ≥60 years (OR = 1.19, p = 0.030), current smoking (OR = 1.71, p = 0.009), COPD (OR = 3.13, p < 0.001), RDW-CV ≥12.8% (OR = 1.09, p = 0.005), ALB <35.5 g/L (OR = 1.04, p = 0.003) and INRS ≥1.86 (OR = 5.04, p < 0.001). The RBE nomogram model demonstrated strong discriminatory power, accuracy and clinical utility across the development, internal validation and external validation cohorts.

Conclusion: In post-TBI patients, the INRS represents a novel predictive biomarker for RBE. The INRS-based nomogram is a clinically applicable and efficient tool for risk stratification and guiding follow-up management to prevent RBE progression.

Background: The treatment strategy for intestinal non-Hodgkin lymphoma (NHL) and the role of surgery warrant reevaluation.

Methods: This study analyzed clinical data from a cohort of 12,047 patients diagnosed with intestinal NHL, extracted from the Korean National Health Insurance System database between 2002 and 2021.

Results: Among these patients, 3,566 (29.6%) were categorized into the surgery group, while 8,481 (70.4%) were included in the nonsurgery group. Surgery was independently associated with both prolonged overall survival (OS) and a favorable prognosis in multivariate analysis (Hazard Ratio [HR] = 0.645, 95% Confidence Interval [CI] = 0.598-0.695, p <.001). The median OS was longer in patients who underwent lymph node dissection during surgery than in patients who did not undergo lymph node dissection (10-year OS with lymph node dissection 63.17% vs. surgery without lymph node dissection 54.78%, p < .001).

Conclusions: To our knowledge, this is the first Korean population-based nationwide study to describe the clinical impact of surgery on the OS of patients with intestinal NHL. A prospective randomized study evaluating strategies to improve the survival of intestinal NHL patients is needed.

Background: No effective treatment strategy for acute respiratory distress syndrome (ARDS) has been established. Conflicting reports on the effects of insulin-like growth factor (IGF)-1 stimulation and the inhibition of IGF-1 receptor (IGF-1R) signalling in tissue injury across several organs have led to hesitation in advancing IGF-1-based treatment strategies for tissue damage.

Objective: We aim to examine whether IGF-1/IGF-1R signalling contributes to recovery from acute lung injury in mouse models and to further explore its potential mechanisms.

Methods: Lipopolysaccharide (LPS) was intratracheally injected into mice to create acute lung injury models. Experiments were conducted to acquire or inhibit IGF-1 signalling through the intratracheal injection of recombinant IGF-1 or JB1, an IGF-1 receptor antagonist during the recovery phase of the models, starting on day 4 after LPS administration. Bone marrow monocyte-derived macrophages (MDMs) cocultured with IGF-1 and/or JB1 were intratracheally injected during the recovery phase.

Results: Inflammatory cell counts and lung injury scores were significantly decreased when recombinant IGF-1 was administered in the later phase, while they increased with the administration of JB1. On day 4 after LPS injection, IGF-1 receptor (IGF-1R, also known as CD221) was strongly expressed on macrophages, particularly in CD11c⁺SiglecF⁺ alveolar macrophages (AMs). Intratracheal injection of MDMs cocultured with IGF-1 decreased lung neutrophil counts, whereas the addition of JB1 to MDMs cocultured with IGF-1 counteracted the effect of IGF-1. JB1 also reduced efferocytosis capacity of AMs in the later phase. In the phagocytosis assay, LPS decreased the efflux capacity of macrophages, but recombinant IGF-1 improved this capacity regardless of the presence or absence of LPS.

Conclusion: IGF-1/IGF-1R signalling in macrophage facilitates the recovery from acute lung injury via enhancing efferocytosis. IGF-1 delivery potentially offers a new treatment strategy for ARDS.