Loss of white matter integrity mediates the association between cortical cerebral microinfarcts and cognitive dysfunction: A longitudinal study.

Cortical cerebral microinfarcts (CMIs) are associated with loss of white matter (WM) integrity and cognitive impairment in cross-sectional studies, while further investigation using longitudinal datasets is required. This study aims to establish the association between cortical CMIs and WM integrity assessed by diffusion-tensor imaging (DTI) measures and to investigate whether DTI measures mediate the relationship between cortical CMIs and cognitive decline. Cortical CMIs were graded on 3T MRI. DTI measures were derived from histogram analysis of mean diffusivity (MD) and fractional anisotropy (FA). Cognitive function was assessed using a neuropsychological test battery. Linear mixed-effect models were employed to examine associations of cortical CMIs with longitudinal changes in DTI measures and cognitive function. Final analysis included 231 patients (71.14 ± 7.60 years). Presence of cortical CMIs at baseline was associated with longitudinal changes in MD median and peak height and FA median and peak height, as well as global cognition (ß = -0.50, 95%CI: -0.91, -0.09) and executive function (ß = -0.77, 95%CI: -1.25, -0.28). MD median mediated the cross-sectional association between cortical CMIs and global cognition. Further studies are required to investigate whether cortical CMIs and loss of WM integrity are causally related or if they are parallel mechanisms that contribute to cognitive decline.

Pro-tumorigenic activity of PYCR1 in gastric cancer through regulating the PI3K/AKT signaling.

Background: The primary objective of this investigation was to assess the impact of pyrroline-5-carboxylate reductase 1 (PYCR1) on the progression of gastric cancer (GC), specifically focusing on tumor growth and metastatic potential. Methods: Surgical specimens from patients with different stages of GC were assayed for PYCR1 expression using immunohistochemistry. PYCR1 expression was manipulated by depletion or overexpression approaches in GC cells, and these cells were applied to explore the functional roles of PYCR1. Expression of apoptosis- and metastasis-related markers was quantified through quantitative real-time PCR and Western blot. Results: Higher PYCR1 expression was ascertained in surgical specimens from patients with GC as compared to noncancerous adjacent tissues. Additionally, PYCR1 overexpression in GC tissues was linked to adverse clinical outcomes. The depletion of PYCR1 in GC cells resulted in a pronounced reduction in proliferation, the induction of apoptosis, and the attenuation of invasion and metastasis. Conversely, its ectopic expression notably augmented proliferation, restricted apoptosis, and stimulated invasion and metastasis. In addition, the knockdown of PYCR1 resulted in a significant elevation in the activation of caspase 3, a key protein involved in apoptosis. This depletion also led to a decrease in the activation or expression of proteins associated with metastasis, such as phosphorylated (p)-phosphatidylinositol 3-kinase (PI3K), p-AKT serine/threonine kinase (AKT), and snail family transcriptional repressor 1 (Snail). Additionally, it resulted in an upregulation of E-cadherin expression. Conversely, the overexpression of PYCR1 notably increased the levels of p-PI3K, p-AKT, and Snail, while simultaneously reducing E-cadherin expression. Conclusion: PYCR1, by activating PI3K/AKT signaling, assumes a crucial role in governing malignant characteristics of GC cells, including proliferation, apoptosis, and metastasis. These findings underscore the promising potential of PYCR1 as a diagnostic biomarker and a target for tailored therapeutic interventions in patients with GC.

Anisometropia and its association with refraction development in highly myopic children.

CLINICAL RELEVANCE: Anisometropia can affect visual development in children. Investigations of anisometropia in high myopes would explore potential causes related to anisometropia, highlighting the management of anisometropia in high myopia. BACKGROUND: The prevalence of anisometropia ranged from 0.6% to 4.3% in general paediatric population and from 7% to 14% in myopes. Anisometropia is regarded as an associated factor for myopia development, while myopia progression is a stimulus driving anisometropic development. The purpose of this study was to investigate the prevalence of anisometropia and its association with refraction development in Chinese children with high myopia. METHODS: In the cohort study, a total of 1,577 highly myopic (spherical equivalent ≤-5.0D) children aged 4-18 years were included. Refractive parameters (dioptre of sphere, dioptre of cylinder, corneal curvature radius, and axial length) of both eyes were measured after cycloplegia. The prevalence and degree of anisometropia were compared among refractive groups (non-parametric tests or chi-square tests), and regression analyses were used to determine associated factors of anisometropia. The statistical significance was set to P < 0.05 (two-tailed). RESULTS: In highly myopic children with a mean (standard deviation) age of 13.06 (2.80) years, the proportions of spherical equivalent anisometropia, cylindrical anisometropia and spherical anisometropia ≥1.00 D were 34.5%, 21.9% and 39.9%, respectively. There was more spherical equivalent anisometropia associated with more severe astigmatism (P for trend <0.001). In the multivariate regression analysis, more spherical equivalent anisometropia, cylindrical anisometropia and spherical anisometropia were associated with higher degrees of astigmatism (standard beta = -0.175, -0.148 and -0.191, respectively). More spherical anisometropia was associated with better spherical power (standard beta = 0.116). CONCLUSION: The proportion of anisometropia in highly myopic children was high, compared with previously reported general population, and more severe anisometropia was associated with higher degree of cylindrical power, but not spherical power.

Association of diet quality with hand grip strength weakness and asymmetry in a multi-ethnic Asian cohort.

Hand grip strength (HGS) is an important diagnostic tool for sarcopenia and a reliable predictor for age-related chronic diseases and mortality. Interventions in nutrition have been shown as a low-cost strategy to maintain muscular strength and mass. However, there are limited data on the effect of diet on HGS in Southeast Asian populations. This study aims to investigate the association of diet quality with HGS weakness and asymmetry in a multi-ethnic population in Singapore. This cross-sectional study used data from the Singapore Multi-Ethnic Cohort (n = 1547). Dietary data were collected using a validated semi-quantitative FFQ and summarised as the Dietary Quality Index - International (DQI-I). HGS was calculated as the maximum value of six measurements from both hands. HGS weakness and asymmetry were defined using well-recognised criteria. Multivariable linear regression and logistic regression were utilised for continuous and binary outcomes, respectively, adjusting for age, sex, ethnicity, physical activity and smoking status. It was found that the highest quartile of DQI-I was significantly associated with higher HGS (ß = 1·11; 95 % CI 0·41, 1·82; Pfor trend < 0·001) and lower odds of HGS asymmetry (OR = 0·71; 95 % CI 0·53, 0·94; Pfor trend = 0·035) and both HGS weakness and asymmetry (OR = 0·50; 95 % CI 0·32, 0·76; Pfor trend = 0·004). Among the different components of DQI-I, only dietary adequacy was significantly associated with higher HGS (Pfor trend < 0·001) and lower odds for both HGS weakness and asymmetry (Pfor trend = 0·006). Our findings support that DQI-I, an indicator of overall diet quality, can be used to provide dietary guidelines for prevention and management of muscle wasting, sarcopenia and frailty.

Cylinder power progression associated with axial length in young children: a two-year follow-up study.

PURPOSE: To describe the association of refraction development and axial length (AL) in young children and provide new insights into the progression of cylinder power. METHODS: Children (2-3 grades) were enrolled from primary schools in Shanghai and followed up for two years. Cycloplegic refraction, AL, and corneal curvature radius were measured. Refraction parameters were compared among groups with different AL, AL1 (AL < 23.5 mm), AL2 (23.5 mm ≤ AL < 24.5 mm), and AL3 (AL ≥ 24.5 mm). Multiple regression analysis was used to explore risk factors of diopter of cylinder (DC) progression. RESULTS: In total, out of 6891 enrolled children, 5961 participants (7-11 yrs) were included in the final analysis. Over the two-year period, the cylinder power significantly changed, and those with longer AL had more rapid DC progression over the two years (AL1, -0.09 ± 0.35 D; AL2, -0.15 ± 0.39 D; AL3, -0.29 ± 0.44 D) (P < 0.001). The change in DC was independently associated with AL at baseline (P < 0.001). The proportion of with-the-rule astigmatism increased from 91.3% to 92.1% in AL1 group, from 89.1% to 91.8% in AL2 group and from 87.1% to 92.0% in AL3 group. CONCLUSIONS: Young children with long AL experienced rapid progression of cylinder power. Both the control of myopia progression and attention to the correction of astigmatism are necessary in the health management of children with long AL. The significantly increased AL in participants might contribute to both the extent and direction of astigmatism.

Cerebral microinfarcts revisited: Detection, causes, and clinical relevance.

Cerebral microinfarcts (CMIs) are small ischemic lesions invisible to the naked eye at brain autopsy, while the larger ones (0.5-4 mm in diameter) have been visualized in-vivo on magnetic resonance imaging (MRI). CMIs can be detected on diffusion-weighted imaging (DWI) as incidental small DWI-positive lesions (ISDPLs) and on structural MRI for those confined to the cortex and in the chronic phase. ISDPLs may evolve into old cortical-CMIs, white matter hyperintensities or disappear depending on their location and size. Novel techniques in neuropathology and neuroimaging facilitate the detection of CMIs, which promotes understanding of these lesions. CMIs have heterogeneous causes, involving both cerebral small- and large-vessel disease as well as heart diseases such as atrial fibrillation and congestive heart failure. The underlying mechanisms incorporate vascular remodeling, inflammation, blood-brain barrier leakage, penetrating venule congestion, cerebral hypoperfusion, and microembolism. CMIs lead to clinical outcomes, including cognitive decline, a higher risk of stroke and mortality, and accelerated neurobehavioral disturbances. It has been suggested that CMIs can impair brain function and connectivity beyond the microinfarct core and are also associated with perilesional and global cortical atrophy. This review aims to summarize recent progress in studies involving both cortical-CMIs and ISDPLs since 2017, including their detection, etiology, risk factors, MRI correlates, and clinical consequences.

Exploration and validation of the Ki67, Her-2, and mutant P53 protein-based risk model, nomogram and lymph node metastasis model for predicting colorectal cancer progression and prognosis.

Introductions: Identifying biological markers of colorectal cancer (CRC) development and prognosis and exploring the intrinsic connection between these molecular markers and CRC progression is underway. However, a single molecular tumor marker is often difficult to assess and predict the progression and prognosis of CRC. Consequently, a combination of tumor-related markers is much needed. Ki67, Her-2, and mutant P53 (MutP53) proteins play pivotal roles in CRC occurrence, progression and prognosis. Methods: Based on the expressions by immunochemistry, we developed a risk model, nomogram and lymph node metastasis model by R software and Pythons to explore the value of these proteins in predicting CRC progression, prognosis, and examined the relationship of these proteins with the CRC clinicopathological features from 755 (training set) and 211 CRC (validation set) patients collected from the hospital. Results: We found that Ki67 expression was significantly correlated with T-stage, N-stage, TNM-stage, vascular invasion, organization differentiation, and adenoma carcinogenesis. Moreover, Her-2 expression was significantly correlated with T-stage, N-stage, TNM-stage, vascular and nerve invasion, pMMR/dMMR, signet ring cell carcinoma, and organization differentiation. MutP53 expression was significantly correlated with T-stage, N-stage, TNM-stage, vascular and nerve invasion, adenoma carcinogenesis, signet ring cell carcinoma, organization differentiation, and pMMR/dMMR. Increased expression of each of the protein indicated a poor prognosis. The established risk model based on the three key proteins showed high predictive value for determining the pathological characteristics and prognosis of CRC and was an independent influencer for prognosis. The nomogram prediction model, which was based on the risk model, after sufficient evaluation, showed more premium clinical value for predicting prognosis. Independent cohort of 211 CRC patients screened from the hospital verified the strong predictive efficacy of these models. The utilization of the XGBoost algorithm in a lymph node metastasis model, which incorporates three crucial proteins, demonstrated a robust predictive capacity for lymph node metastasis. Discussion: The risk model, nomogram and lymph node metastasis model have all provided valuable insights into the involvement of these three key proteins in the progression and prognosis of CRC. Our study provides a theoretical basis for further screening of effective models that utilize biological markers of CRC.

Angioedema in the Absence of C1 Esterase Inhibitor Deficiency in a Young Patient With Anti-dsDNA Negative Lupus Nephritis.

Hereditary angioedema (HAE) is an autosomal dominant condition marked by a lack of functioning C1 esterase inhibitor (C1-INH). In contrast, acquired angioedema (AAE) due to a deficiency of C1 esterase inhibitor (AAE-C1-INH) may be the manifestation of an underlying lymphoproliferative, neoplastic, or autoimmune condition. Both are potentially fatal. The C1q protein is normal in HAE but low in AAE. A third mechanism has been reported to cause angioedema, especially in systemic lupus erythematosus (SLE) patients. AAE, which happens in association with SLE, may respond well to steroids. Here we present a case of AAE in a young female with SLE that led to upper airway compromise, requiring endotracheal intubation. Early detection and treatment of such cases can lead to an outstanding prognosis by preventing airway compromise and anoxic brain injury. Even though it is a condition of either very young or middle-aged patients, practitioners must be aware of this uncommon disease linked with SLE in adolescents and young adults.

Genomic analysis of matrix metalloproteinases affecting the prognosis and immunogenic profile of gastric cancer.

This study systematically and comprehensively analyzed the characteristics of matrix metalloproteinases (MMPs) in gastric cancer (GC) and revealed the relationship between MMPs and prognoses, clinicopathological features, tumor microenvironment, gene mutations, and drug therapy response in patients with GC. Based on the mRNA expression profiles of 45 MMP-related genes in GC, we established a model that classified GC patients into three groups based on cluster analysis of the mRNA expression profiles. The 3 groups of GC patients showed significantly different prognoses as well as tumor microenvironmental characteristics. Next, we used Boruta's algorithm and PCA method to establish an MMP scoring system and found that lower MMP scores were associated with better prognoses, lower clinical stages, better immune cell infiltration, lower degrees of immune dysfunction and rejection, and more genetic mutations. Whereas a high MMP score was the opposite. These observations were further validated with data from other datasets, showing the robustness of our MMP scoring system. Overall, MMP could be involved in the tumor microenvironment (TME), clinical features, and prognosis of GC. An in-depth study of MMP patterns can better understand the indispensable role of MMP in the development of GC and reasonably assess the survival prognosis, clinicopathological features, and drug efficacy of different patients, thus providing clinicians with a broader vision of GC progression and treatment.

Association of clinical outcomes and the predictive value of T lymphocyte subsets within colorectal cancer patients.

Introduction: Tumor immunity is a hot topic in tumor research today, and human immunity is closely related to tumor progression. T lymphocyte is an important component of human immune system, and the changes in their subsets may influence the progression of colorectal cancer (CRC) to some extent. This clinical study systematically describes and analyzes the association of CD4+ and CD8+ T-lymphocyte content and CD4+/CD8+ T-lymphocyte ratio with CRC differentiation, clinical pathological stage, Ki67 expression, T-stage, N-stage, carcinoembryonic antigen (CEA) content, nerve and vascular infiltration, and other clinical features, as well as preoperative and postoperative trends. Furthermore, a predictive model is constructed to evaluate the predictive value of T-lymphocyte subsets for CRC clinical features. Methods: Strict inclusion and exclusion criterion were formulated to screen patients, preoperative and postoperative flow cytometry and postoperative pathology reports from standard laparoscopic surgery were assessed. PASS and SPSS software, R packages were invoked to calculate and analyze. Results: We found that a high CD4+ T-lymphocyte content in peripheral blood and a high CD4+/CD8+ ratio were associated with better tumor differentiation, an earlier clinical pathological stage, lower Ki67 expression, shallower tumor infiltration, a smaller number of lymph node metastases, a lower CEA content, and a lower likelihood of nerve or vascular infiltration (P < 0.05). However, a high CD8+ T-lymphocyte content indicated an unpromising clinical profile. After effective surgical treatment, the CD4+ T-lymphocyte content and CD4+/CD8+ ratio increased significantly (P < 0.05), while the CD8+ T-lymphocyte content decreased significantly (P < 0.05). Further, we comprehensively compared the merits of CD4+ T-lymphocyte content, CD8+ T-lymphocyte content, and CD4+/CD8+ ratio in predicting the clinical features of CRC. We then combined the CD4+ and CD8+ T-lymphocyte content to build models and predict major clinical characteristics. We compared these models with the CD4+/CD8+ ratio to explore their advantages and disadvantages in predicting the clinical features of CRC. Discussion: Our results provide a theoretical basis for the future screening of effective markers in reflecting and predicting the progression of CRC. Changes in T lymphocyte subsets affect the progression of CRC to a certain extent, while their changes also reflect variations in the human immune system.

Effect of Repeated Low-level Red Light on Myopia Prevention Among Children in China With Premyopia: A Randomized Clinical Trial.

Importance: Myopia is a global concern, but effective prevention measures remain limited. Premyopia is a refractive state in which children are at higher risk of myopia, meriting preventive interventions. Objective: To assess the efficacy and safety of a repeated low-level red-light (RLRL) intervention in preventing incident myopia among children with premyopia. Design, Setting, and Participants: This was a 12-month, parallel-group, school-based randomized clinical trial conducted in 10 primary schools in Shanghai, China. A total of 139 children with premyopia (defined as cycloplegic spherical equivalence refraction [SER] of -0.50 to 0.50 diopter [D] in the more myopic eye and having at least 1 parent with SER ≤-3.00 D) in grades 1 to 4 were enrolled between April 1, 2021, and June 30, 2021; the trial was completed August 31, 2022. Interventions: Children were randomly assigned to 2 groups after grade stratification. Children in the intervention group received RLRL therapy twice per day, 5 days per week, with each session lasting 3 minutes. The intervention was conducted at school during semesters and at home during winter and summer vacations. Children in the control group continued usual activities. Main Outcomes and Measures: The primary outcome was the 12-month incidence rate of myopia (defined as SER ≤-0.50 D). Secondary outcomes included the changes in SER, axial length, vision function, and optical coherence tomography scan results over 12 months. Data from the more myopic eyes were analyzed. Outcomes were analyzed by means of an intention-to-treat method and per-protocol method. The intention-to-treat analysis included participants in both groups at baseline, while the per-protocol analysis included participants in the control group and those in the intervention group who were able to continue the intervention without interruption by the COVID-19 pandemic. Results: There were 139 children (mean [SD] age, 8.3 [1.1] years; 71 boys [51.1%]) in the intervention group and 139 children (mean [SD] age, 8.3 [1.1] years; 68 boys [48.9%]) in the control group. The 12-month incidence of myopia was 40.8% (49 of 120) in the intervention group and 61.3% (68 of 111) in the control group, a relative 33.4% reduction in incidence. For children in the intervention group who did not have treatment interruption secondary to the COVID-19 pandemic, the incidence was 28.1% (9 of 32), a relative 54.1% reduction in incidence. The RLRL intervention significantly reduced the myopic shifts in terms of axial length and SER compared with the control group (mean [SD] axial length, 0.30 [0.27] mm vs 0.47 [0.25] mm; difference, 0.17 mm [95% CI, 0.11-0.23 mm]; mean [SD] SER, -0.35 [0.54] D vs -0.76 [0.60] D; difference, -0.41 D [95% CI, -0.56 to -0.26 D]). No visual acuity or structural damage was noted on optical coherence tomography scans in the intervention group. Conclusions and Relevance: In this randomized clinical trial, RLRL therapy was a novel and effective intervention for myopia prevention, with good user acceptability and up to 54.1% reduction in incident myopia within 12 months among children with premyopia. Trial Registration: ClinicalTrials.gov Identifier: NCT04825769.

Guselkumab-Associated Pulmonary Disease and Diffuse Alveolar Hemorrhage with Drug Rash with Eosinophilia and Systemic Symptoms.

Psoriasis is a common skin condition worldwide. Moderate-to-severe disease is treated with biologic or non-biologic disease-modifying anti-rheumatic drugs. These include tumor necrosis factor (TNF)-a inhibitors, interleukin (IL)-17 inhibitors, and IL-23 inhibitors. Case reports of inhibitors of TNF-a and IL-12p40 subunits causing interstitial pneumonia (IP) have been published in the literature, but no case of anti-IL-23p19 subunit biologics causing IP and acute respiratory distress syndrome (ARDS) has been reported before. We report a case of a patient with restrictive lung disease secondary to a body mass index of 36.54 kg/m2, obstructive sleep apnea, and psoriasis, who developed IP and ARDS presumed to be secondary to guselkumab, an anti-IL-23p19 subunit monoclonal antibody. He was on ustekinumab, an anti-IL-12/23p40 for the treatment of psoriasis, but was switched to guselkumab eight months before the presentation, and since then he had been complaining of progressive shortness of breath. He initially presented to the hospital after having drug reaction with eosinophilia and systemic symptoms (DRESS) after being started on amoxicillin for a tooth infection. He was treated with high-dose intravenous steroids but developed progressive shortness of breath. Broad-spectrum antibiotics were added. An extensive infectious, autoimmune, and hypersensitivity work-up was undertaken, which returned negative. A bronchoscopy with bronchoalveolar lavage was performed, which revealed diffuse alveolar hemorrhage (DAH). His lung imaging and oxygenation progressively got worse; hence, no lung biopsy was taken. He was intubated and required inhaled nitric oxide, but due to the lack of improvement, the family elected for comfort measures, and the patient was extubated and passed away. To our knowledge, this is the first case of an association between guselkumab, IP, ARDS, and DAH. Rare instances of DAH with DRESS have been reported before. Whether it was DRESS or guselkumab that caused DAH was uncertain in our patient. Clinicians should monitor for DAH and shortness of breath in patients on guselkumab so that more data can be obtained and studied in the future.

Updated severity and prognosis score of pulmonary alveolar proteinosis: A multi-center cohort study in China.

Background: The high-resolution computed tomography (HRCT) score is an important component of the severity and prognosis score of pulmonary alveolar proteinosis (SPSP). However, the HRCT score in SPSP only considers the extent of opacity, which is insufficient. Methods: We retrospectively evaluated HRCT scores for 231 patients with autoimmune pulmonary alveolar proteinosis (APAP) from three centers of the China Alliance for Rare Diseases. The SPSPII was created based on the overall density and extent, incorporating the SPSP. The severity of APAP patients was assessed using disease severity scores (DSS), SPSP, and SPSPII to determine the strengths and weaknesses of the different assessment methods. We then prospectively applied the SPSPII to patients before treatment, and the curative effect was assessed after 3 months. Results: The HRCT overall density and extent scores in our retrospective analysis were higher than the extent scores in all patients and every original extent score severity group, as well as higher related to arterial partial oxygen pressure (PaO2) than extent scores. The mild patients accounted for 61.9% based on DSS 1-2, 20.3% based on SPSP 1-3, and 20.8% based on SPSPII 1-3. Based on SPSP or SPSPII, the number of severe patients deteriorating was higher in the mild and moderate groups. When applied prospectively, arterial PaO2 differed between any two SPSPII severity groups. The alveolar-arterial gradient in PaO2 (P[A-a]O2), % predicted carbon monoxide diffusing capacity of the lung (DLCO), and HRCT score were higher in the severe group than in the mild and moderate groups. After diagnosis, mild patients received symptomatic treatment, moderate patients received pure whole lung lavage (WLL) or granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy, and severe patients received WLL and GM-CSF therapy. Importantly, the SPSPII in mild and severe groups were lower than baseline after 3 months. Conclusion: The HRCT density and extent scores of patients with APAP were better than the extent score. The SPSPII score system based on smoking status, symptoms, PaO2, predicted DLCO, and overall HRCT score was better than DSS and SPSP for assessing the severity and efficacy and predicting the prognosis. Trial registration: ClinicalTrial.gov, identifier: NCT04516577.

Determinants of Progression and Mortality in Lymphangioleiomyomatosis.

BACKGROUND: Lymphangioleiomyomatosis is a progressive diffuse cystic lung disease with approximately 85% survival at 10 years. The determinants of disease progression and mortality after the introduction of sirolimus therapy and vascular endothelial growth factor D (VEGF-D) as a biomarker have not been well defined. RESEARCH QUESTION: Which factors, including VEGF-D and sirolimus therapy, influence disease progression and survival prognosis in patients with lymphangioleiomyomatosis? STUDY DESIGN AND METHODS: The progression dataset and the survival dataset included 282 and 574 patients, respectively, from Peking Union Medical College Hospital, Beijing, China. A mixed-effects model was used to compute the rate of decline in FEV1, and generalized linear models were used to identify variables affecting FEV1 decline. A Cox proportional hazards model was used to explore the association between clinical variables and the outcomes of death or lung transplantation in patients with lymphangioleiomyomatosis. RESULTS: VEGF-D levels and sirolimus treatment were associated with FEV1 changes and survival prognosis. Compared with patients with VEGF-D of < 800 pg/mL at baseline, patients with VEGF-D of ≥ 800 pg/mL lost FEV1 faster (SE, -38.86 mL/y; 95% CI, -73.90 to -3.82 mL/y; P = .031). The 8-year cumulative survival rates of patients with VEGF-D of ≥ 2,000 pg/mL and < 2,000 pg/mL were 82.9% and 95.1%, respectively (P = .014). The generalized linear regression model also demonstrated the benefit of delaying the decline of FEV1 by 65.56 mL/y (95% CI, 29.06-102.06 mL/y) in patients treated with sirolimus compared with those without sirolimus (P < .001). The 8-year risk of death was reduced by 85.1% (hazard ratio, 0.149; 95% CI, 0.075-0.299) after sirolimus treatment. After inverse treatment probability weighting, the risks of death in the sirolimus group were reduced by 85.6%. CT scan results of grade III severity were associated with worse progression than results of grades I or II severity. Patients with baseline FEV1 of 70% predicted or St. George's Respiratory Questionnaire Symptoms domain 50 or higher predicted a higher risk of worse survival. INTERPRETATION: Serum VEGF-D levels, a biomarker of lymphangioleiomyomatosis, are associated with disease progression and survival. Sirolimus therapy is associated with slower disease progression and better survival in patients with lymphangioleiomyomatosis. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03193892; URL: www. CLINICALTRIALS: gov.

Development and external validation of a machine learning-based prediction model for the cancer-related fatigue diagnostic screening in adult cancer patients: a cross-sectional study in China.

PURPOSE: Cancer-related fatigue (CRF) is the most common symptom in cancer patients and may interfere with patients' daily activities and decrease survival rate. However, the etiology of CRF has not been identified. Diagnosing CRF is challenging. Thus, our study aimed to develop a CRF prediction model in cancer patients, using data that healthcare professionals routinely obtained from electronic health records (EHRs) based on the 3P model and externally validate this model in an independent dataset collected from another hospital. METHODS: Between April 2022 and September 2022, a cross-sectional study was conducted on adult cancer patients at two first-class tertiary hospitals in China. Data that healthcare professionals routinely obtained from electronic health records (EHRs) based on the 3P model were collected. The outcome measure was according to ICD-10 diagnostic criteria for CRF. Data from one hospital (n = 305) were used for model development and internal validation. An independent data set from another hospital (n = 260) was utilized for external validation. logistic regression, random forest (RF), Naive Bayes (NB), and extreme gradient boosting (XGBoost) were constructed and compared. The model performance was evaluated in terms of both discrimination and calibration. RESULTS: The prevalence of CRF in the two centers was 57.9% and 56.1%, respectively. The Random Forest model achieved the highest AUC of 0.86 among the four types of classifiers in the internal validation. The AUC of RF and NB were above 0.7 in the external validation, suggesting that the models also have an acceptable generalization ability. CONCLUSIONS: The incidence of CRF remains high and deserves more attention. The fatigue prediction model based on the 3P theory can accurately predict the risk of CRF. Nonlinear algorithms such as Random Forest and Naive Bayes are more suitable for diagnosing and evaluating symptoms.

Niacin-Induced Syncope in a Middle-Aged Male: When an Over-the-Counter Vitamin Goes Wrong.

Niacin is an essential vitamin with lipid-modifying properties. It is readily available in many over-the-counter (OTC) supplements. However, the use of niacin can lead to undesirable adverse reactions, including flushing, nausea, hyperglycemia, etc. Here, we present a rare case of niacin-induced syncope caused by a sudden increase in dosage in a middle-aged male. Extensive history, examination, and cardiovascular investigation were obtained to rule out various common etiologies of syncope. We also discuss the utility of niacin as a nutritional supplement, as most individuals obtain sufficient niacin intake from foods and beverages. As a treatment for dyslipidemia, niacin no longer exhibits cardiovascular benefits in the contemporary statin era. We argue that an additional niacin supplement is both unnecessary and potentially harmful. Therefore, niacin supplementation should be cautiously taken with no additional health benefits and frequent deleterious effects.

Effect of Ocular Magnification on Macular Choroidal Thickness Measurements Made Using Optical Coherence Tomography in Children.

PURPOSE: To evaluate the relationship between ocular magnification correction and macular choroidal thickness (ChT) measurements in children, and to demonstrate when ocular magnification correction is necessary. METHODS: Chinese children aged 6-9 years with various refractive statuses were included. Swept-source optical coherence tomography was used to measure macular ChT. A self-designed program was adopted to simulate ChT changes in each sector of the ETDRS grid in the macula under various simulated axial lengths (ALs). RESULTS: ChT measurements were not affected for all simulated ALs in over 95% of the individuals in the central fovea. In the inferior, superior, and temporal parafoveal sectors, the extent of AL that may include 95% of the individuals narrowed from approximately 22.0 mm to 27.2 mm. In the nasal parafoveal sector and inferior, superior, and temporal perifoveal sectors, the extent of AL that may include 95% of the individuals became even narrower, from approximately 22.8 mm to 26.0 mm. The narrowest extent was observed in the perifoveal nasal sector, ranging from 23.3 mm to 25.5 mm. The effect of ocular magnification was more significant in hyperopes than in myopes in the inferior parafoveal sector and temporal, superior, and nasal perifoveal sectors. CONCLUSION: During macular ChT measurements, ocular magnification correction is not necessary in the central fovea. However, ocular magnification should be corrected normally in the nasal perifoveal region and in individuals with ALs shorter than 22.8 mm or longer than 26.0 mm in the remaining macular regions.

Gene mutations in sporadic lymphangioleiomyomatosis and genotype-phenotype correlation analysis.

BACKGROUND: Sporadic lymphangioleiomyomatosis (S-LAM) is a rare neoplasm with heterogeneous clinical features that is conventionally considered to be related to TSC2. This study serves to elucidate the mutation landscape and potential correlation between S-LAM genomic profiles and clinical phenotypes. METHODS: Genomic profiles of 22 S-LAM patients were obtained by sequencing genomic DNA and cell-free DNA from various specimens using an NGS (next-generation sequencing)-based tumor-driver gene panel. Detected mutations were summarized. Symptoms, serum vascular endothelial growth factor D (VEGF-D) values, pulmonary function, and six-minute walk distance (6MWD) were compared among groups with different TSC2 status and genotypes to analyze genotype-phenotype correlations. RESULTS: 67 Variants in 43 genes were detected, with a TSC2 mutation detection rate of 68.2%. The TSC2 detection rate was similar in specimens obtained either through transbronchial lung biopsy (TBLB) or surgical lung biopsy (70.0% vs. 69.2%, p > 0.05). A novel mutation in VEZF1 (c.A659G) was detected in four participants and may represent a mild disease state. TSC2 mutation was significantly related to a shorter 6MWD (p < 0.05), and a higher percentage of VEGF-D over 800 pg/mL (p < 0.05); stop-gain mutation was significantly related to a higher prevalence of pneumothorax. CONCLUSIONS: Tumor-driver mutations in genes other than TSC2 may have a role in S-LAM, and TBLB specimens are practical alternatives for genomic analysis. TSC2 mutation detectability and types are related to the disease severity and phenotypes of S-LAM.