Journal of clinical medicine research最新文献

Background: Impaired social functioning is one of the core symptoms of schizophrenia (SCZ). Genetic factors have also been implicated in SCZ. To contribute to the discussion on the involvement of genetic factors in SCZ, we evaluated the social functioning of first-degree relatives (FR) of patients with SCZ.

Methods: This was a non-interventional observational study. We examined social functioning using the Japanese version of the Social Functioning Scale (SFS-J) in three groups: SCZ, SCZ FR, and healthy controls (HC). The effects of the groups (SCZ, FR, and HC) on social functioning were evaluated using analysis of covariance. In addition, the cutoff value for SCZ in the SFS total score was calculated, and the trend in the proportion of individuals below the cutoff value in each group was evaluated.

Results: Data from 256 subjects (SCZ (n = 44), FR (n = 26), and HC (n = 186)) were analyzed. Group, years of education, intelligence quotient (IQ), and sex were found to be significant factors affecting SFS total scores. The proportion of SFS scores < 140 (the cutoff value for SCZ) was 9.1% in HC, 57.7% in FR, and 95.4% in SCZ, showing a continuous increase in the proportion of SFS scores < 140 across the three groups (P < 0.0001).

Conclusions: In social functioning assessed by SFS, the score for FR was intermediate between those of SCZ and HC. The results of this study suggest that genetic factors may influence social functioning scores in SCZ and FR.

Background: Graft-versus-host disease (GvHD) is a serious complication of allogeneic hematopoietic cell transplantation, and the major cause of post-transplant mortality and morbidity. If steroid treatment as first-line therapy fails, treatment options are limited. Ruxolitinib (Ruxo) as well as extracorporeal photopheresis (ECP) showed high efficacy in the treatment of steroid-refractory (SR) acute and chronic GvHD.

Methods: We interrogated data from 68 adult and pediatric patients with SR acute and chronic GvHD, between 2017 and 2024, who received either Ruxo plus ECP (Ruxo + ECP, n = 31) or Ruxo alone (Ruxo, n = 37). Endpoints were to compare the overall response rates (ORRs) including complete response (CR) and partial response (PR) of acute and chronic GvHD at last encounter, and the percentage of patients with history of acute GvHD, who progressed to chronic GvHD at 1 year, 1-year non-relapse mortality (NRM), graft-versus-host disease relapse-free survival (GRFS) and survival outcomes at 3 years.

Results: Patient, disease, and transplant characteristics were well balanced, except for more severe acute GvHD in Ruxo + ECP arm (66.6% vs. 18.5%, P = 0.007) and longer Ruxo treatment in Ruxo alone arm (11 vs. 7 months, P = 0.05). The ORRs were 58% for Ruxo + ECP arm compared to 49% in Ruxo alone arm (P = 0.002) at last encounter and the duration of response was 17.6 versus 9 months (P = 0.3171), respectively. In both arms, 87% and 93% of patients could taper steroids rapidly by 50% and 16%. At 1 year, cumulative incidence of chronic GvHD was higher after Ruxo versus Ruxo + ECP, being 55% (95% CI: 42-69%) vs. 26% (95% CI: 22-64%) (P = 0.018). No statistically significant difference in 1-year NRM, relapse, and GRFS and survival at 3 years was observed.

Conclusion: Our data suggest improved long-term control of acute and chronic GvHD by combining Ruxo plus ECP compared with Ruxo alone.

Background: Adenomyosis and endometriosis are estrogen-driven disorders with a recognized potential for malignant transformation, particularly through atypical endometriosis. The molecular and immune mechanisms underlying this progression remain incompletely understood. However, clinical factors such as age, comorbidities, and hormonal therapy can also influence lesion behavior. The objectives were to comprehensively evaluate hormonal, proliferative-apoptotic, cell-cycle, and immune-microenvironmental alterations across the spectrum of endometrial lesions and to assess the impact of prior endometrial hyperplasia and associated clinical parameters.

Methods: Seventy-seven formalin-fixed paraffin-embedded cases were stratified into five groups: eutopic endometrium (n = 17), adenomyosis (n = 27), typical endometriosis (n = 16), atypical endometriosis (n = 10), and endometriosis-associated carcinoma (n = 24). Immunohistochemical analysis included estrogen receptor, progesterone receptor, Ki67, BCL2, P53, cyclin D1, CDK4, P16, FOXP3, CD68, and CD163. Clinical variables including age, comorbidities, and medication history were integrated into statistical analysis. Marker expression was quantified semi-quantitatively, and clinical associations with prior endometrial hyperplasia were evaluated using Kruskal-Wallis and Mann-Whitney U tests.

Results: Cyclin D1, CDK4, and P16 expression progressively increased from benign lesions to carcinoma (P < 0.001). FOXP3⁺ T cells and CD163⁺ M2 macrophages accumulated in atypical endometriosis and carcinoma, indicating an immunosuppressive microenvironment. Patients with prior atypical endometrial hyperplasia demonstrated significantly higher expression of proliferative (cyclin D1, CDK4, and P16) and immune-suppressive markers (FOXP3 and CD163) and a 66% progression to carcinoma. Clinical background factors were statistically adjusted and did not alter the overall progression trend.

Conclusion: The stepwise evolution from benign endometrial lesions to carcinoma is driven by coordinated proliferative and immune microenvironmental shifts, potentiated by a history of atypical endometrial hyperplasia. Integrating immunohistochemical and clinical risk factors may enhance early identification and surveillance of patients at high risk for endometriosis-associated carcinoma.

Background: Atrial fibrillation (AF) is a frequent but variably reported complication of thyrotoxicosis, with mechanisms that extend beyond thyroid hormone excess. Clarifying its prevalence and determinants may guide early detection and management.

Methods: We conducted a retrospective cross-sectional study of adults with thyrotoxicosis. Clinical, biochemical, and electrocardiographic data were reviewed. Associations between variables and AF were assessed using generalized linear models with robust errors, and results expressed as adjusted odds ratios (ORs) with 95% confidence intervals (CIs).

Results: Among 801 patients with thyrotoxicosis, 65 had AF, yielding a prevalence of 8.1% (95% CI: 6.3 - 10.2). Compared with non-AF patients, those with AF were older, more often male (48% vs. 20%), and more frequently had chronic kidney disease, dyslipidemia, diabetes, heart failure (HF), cerebrovascular disease, and thyroid crisis (all P < 0.01). In multivariable analysis, independent determinants included age 35 - 60 years (adjusted OR 5.48; 95% CI: 2.03 - 14.83), age > 60 years (adjusted OR 11.39; 95% CI: 3.43 - 37.76), male sex (adjusted OR 3.38; 95% CI: 1.70 - 6.30), HF (adjusted OR 11.25; 95% CI: 2.85 - 44.54), and thyroid crisis (adjusted OR 61.84; 95% CI: 21.89 - 181.32). Thyroid hormone levels were not independently associated with AF.

Conclusion: AF was observed in approximately 8% of patients with thyrotoxicosis. The findings suggested that clinical vulnerabilities - older age, male sex, HF, and thyroid crisis - were more strongly associated with AF than thyroid hormone levels. These results supported targeted AF screening in high-risk thyrotoxic patients and indicated that rhythm management should consider patient susceptibility alongside restoring euthyroidism.

Background: Febrile patients with tachycardia present diverse profiles that complicate triage. Although the Emergency Severity Index (ESI) is widely used in Thailand, inter-rater variability limits consistency. Machine learning (ML) may enhance reliability using routinely collected triage data. The objectives were to develop and evaluate ML models predicting ESI levels 1-3 in febrile tachycardic adults and identify the best model for clinical use.

Methods: This diagnostic prediction study analyzed adults with fever (≥ 37.6 °C) and pulse rate > 100 beats per minute in the triage area of Lampang Hospital, Thailand, during June - August 2024. Patients with complete data were included, whereas referrals and expert-disagreement cases were excluded. Expert-assigned ESI levels were the outcome. Thirteen routinely collected triage variables were evaluated as candidate predictors. The dataset (n = 500) was randomly split 80:20 into development and testing sets. Random forest, extreme gradient boosting (XGBoost), and gradient boosting machine models were developed using five-fold cross-validation with class-weighting for imbalance correction. Performance was assessed using area under the receiver operating characteristic curve (AuROC), calibration, and confusion matrices, with attention to clinically relevant misclassification.

Results: XGBoost demonstrated the best discrimination with AuROC values of 1.00 (confidence interval (CI): 0.99 - 1.00), 0.94 (CI: 0.89 - 0.98), and 0.97 (CI: 0.93 - 1.00) for ESI levels 1-3 in the test set. Calibration showed the lowest Brier scores, and misclassification was minimal, supporting strong predictive consistency across categories.

Conclusions: XGBoost was selected for integration into the Smart ER system as the Thailand Triage Prediction System (TTPS), providing real-time prediction to enhance triage accuracy, support decision-making, and improve workflow.

Background: Stromal cell-derived factor-1 (SDF-1) is a chemokine that regulates atherogenesis, angiogenesis, and multiple physiological processes. Dyslipidemia can contribute to low plasma SDF-1 disturbing its vascular repair functions and elevating cardiovascular risk. Statin therapy is recommended for patients with acute coronary syndrome irrespective of low-density lipoprotein-cholesterol (LDL-C) levels. This study aimed to evaluate the potential associations of plasma SDF-1 levels with LDL-C levels, coronary occlusion-based disease severity, low left ventricular ejection fraction (LVEF) values, and statin therapy in patients with unstable angina (UA).

Methods: Patients with new UA (n = 108) were selected from Coronary Care Unit, King Abdulaziz University Hospital. The exclusion criteria included previous history of myocardial infarction, cardiac valvular problems, myocarditis, liver dysfunction, and recent acute infection. The demographic and clinical features were collected. Disease severity and LVEF values were determined. Plasma SDF-1, LDL-C, and troponin levels were measured.

Results: There were poor correlations between plasma SDF-1 level, and sociodemographic features and risk factors except with LDL-C, where it showed a significant correlation. Furthermore, plasma SDF-1 showed non-significant variations with LVEF values and troponin peak levels. In contrast, plasma SDF-1 declined significantly in statin-treated patients, regardless of LDL-C level, compared with those untreated. The receiver operating characteristic (ROC) curve for SDF-1 test showed good accuracy.

Conclusion: In patients with severe UA, plasma SDF-1 level showed significant variations with LDL-C levels and statin therapy suggesting that it can give insight into response to statin therapy regardless of LDL-C level. The ROC analysis showed favorable characteristics suggesting a potential usefulness of plasma SDF-1 assay to discriminate the statin-treated patients from those untreated. This novel approach highlights SDF-1 potential as a biomarker for monitoring statin therapy and predicting risks for adverse events in UA. Furthermore, it could pave the way for longitudinal studies with repeated measurements of plasma SDF-1 to evaluate its role as a prognostic indicator for major adverse cardiovascular events besides the other cardiovascular disease risk factors.

Background: Inflammatory bowel disease (IBD) is linked to high risks of depression and anxiety. Stigma, limited mental health awareness, and barriers to access continue to contribute to underdiagnosis in Saudi Arabia. This study aimed to determine the prevalence of depression and anxiety among IBD patients, identify related risk factors, and assess barriers to mental health treatment.

Methods: A cross-sectional study including 92 IBD patients from gastroenterology clinics at King Faisal and Al-Noor hospitals was conducted. Data were collected through face-to-face, phone interviews, and an online Arabic questionnaire assessing sociodemographic, IBD-related factors, and mental health information using Patient Health Questionnaire-2 (PHQ-2) and Generalized Anxiety Disorder-7 (GAD-7). Analysis employed Chi-square, Fisher's exact, and logistic regression model to determine associations.

Results: Among 92 patients, 15.2% had symptoms of anxiety, depression, or both. Screening detected 19.6% with depressive symptoms (PHQ-2) and 46.7% with anxiety symptoms (GAD-7), with 17.4% experiencing severe anxiety symptoms. Saudi nationality (OR = 40.15, P = 0.035) was significantly linked to clinical diagnoses. Shorter disease duration (< 6 months, P = 0.017; 1-3 years, P = 0.011), was associated with lower odds of anxiety symptoms, while recent exacerbations (< 3 months, P = 0.012) were associated with increased risk of anxiety symptoms. Higher risk of depression symptoms was associated with recent exacerbations (OR = 7.51, P = 0.055) and smoking (OR = 5.04, P = 0.072). Barriers included stigma (8.7%), cost (6.5%), and concerns about medication side effects (40.2%).

Conclusion: The burden of undiagnosed anxiety and depression is significant among IBD patients in Makkah. Routine screening, stigma reduction, and integrated mental health care are essential.

Background: Several prognostic scores and molecular patterns have been developed to predict increased in-hospital mortality in septic patients. This prospective study aimed to evaluate the prognostic value of systemic inflammatory response syndrome (SIRS), Sequential Organ Failure Assessment (SOFA), quick SOFA (qSOFA), lactate quick SOFA (LqSOFA) and cytokine production levels in emergency department sepsis patients to predict in-hospital mortality.

Methods: A total of 106 septic patients were enrolled. Baseline SOFA, SIRS, qSOFA and LqSOFA scores were calculated, and plasma levels of interleukin (IL)-6, IL-10, tumor necrosis factor-α (TNF-α) and interleukin-33 receptor (IL-33R) were measured on admission.

Results: SOFA, qSOFA, LqSOFA scores were significantly lower in sepsis survivors. IL-33R levels were significantly higher in non-survivors (P = 0.021). The best predictive score for sepsis based on the area under the receiver operating characteristic (ROC) curve was qSOFA (0.764, 95% confidence interval (CI) = 0.663 - 0.866), followed by LqSOFA (0.738, 95% CI = 0.63 - 0.845), SOFA (0.713, 95% CI = 0.604 - 0.822) and SIRS (0.603, 95% CI = 0.478 - 0.729). The addition of IL-33R levels (cut-off values > 55,393 pg/mL) to qSOFA and SOFA significantly increased the diagnostic accuracy of both scores with area under the curve (AUC) of 0.78 (95% CI = 0.695 - 0.85) and 0.740 (95% CI = 0.636 - 0.844), respectively. When evaluating early (within 72 h) in-hospital mortality, both IL-10 and IL-33R were significantly higher in non-survivors (124 pg/mL vs. 41 pg/mL in survivors, 195,610 pg/mL vs. 62,767 pg/mL in survivors, respectively). When added to qSOFA and SOFA scores (cut-off levels 74.5 pg/mL and 55,393 pg/mL for IL-10 and IL-33R, respectively), they significantly increased their diagnostic accuracy.

Conclusions: Sepsis prognostic scores were significantly lower in sepsis survivors. IL-10 levels had a significant impact in predicting early (within 72 h) in-hospital mortality and IL-33R levels in predicting both early and total in-hospital mortality, especially when combined with SOFA and qSOFA scores.

Primary bilateral macronodular adrenocortical hyperplasia (PBMAH) is a heterogeneous disorder, with clinical spectrum ranging from subclinical to severe overt Cushing syndrome (CS). Armadillo repeat containing 5 (ARMC5) mutations, found in 20-55% of cases, are often associated with more severe disease, and specific genotypes may correlate with distinct phenotypes. A 60-year-old woman was admitted with a 1-year history of progressive weight gain and hypokalemia, alongside a 13-year history of refractory hypertension. She exhibited classic CS features and metabolic complications, including hypertension and diabetes. Laboratory tests revealed elevated cortisol, suppressed adrenocorticotropic hormone (ACTH), and positive low- and high-dose dexamethasone suppression tests. Contrast-enhanced computed tomography (CT) showed bilateral irregular macronodular adrenal masses. Adrenal venous sampling (AVS) demonstrated no lateralization (lateralization index < 4). Whole-exome sequencing of peripheral blood leukocytes identified a novel ARMC5 mutation (c.534_555dup, p.Ser186Profs*19). A right adrenalectomy was performed in 2023. Although symptoms improved, cortisol levels remained significantly elevated. Consequently, a left adrenalectomy was performed 15 months later in 2024, which led to marked improvement in her CS symptoms, biomarker levels, and metabolic complications. This case report describes a novel ARMC5 mutation site in a PBMAH patient who ultimately required bilateral adrenalectomy. While AVS combined with CT can help determine the dominant side for surgery, patients with ARMC5 mutations and symmetrically sized tumors often require bilateral adrenalectomy for cure.