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.

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.

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.

Accumulation of plasma levels of anthocyanins following multiple saskatoon berry supplements.

1. Anthocyanins are a subgroup of flavonoids responsible for the blue, purple and red color of many fruits, flowers and leaves. Consumption of foods rich in anthocyanins is associated with a reduced risk of cardiovascular disease and cancer. Most food intervention studies employ once or twice per day dose schedules. 2. The current study demonstrated that plasma concentrations of cyanidin-3-galactoside and cyanidin-3-xyloside, the two major components of saskatoon berries, were significantly increased following three consecutive saskatoon berry supplements 4 hours apart. This accumulation is due to the residual concentrations of anthocyanins at the time of second and third supplements. 3. Accumulation was especially pronounced for peonidin-3-glucoside and peonidin-3-galactoside, the methylated metabolites of cyanidin-3-glucoside and cyanidin-3-galactoside, respectively. Little or no accumulation was observed for cyanidin-3-arabinoside and cyanidin-3-glucoside, two other components of saskatoon berries, possibly due to their short half-lives. 4. Thus, taking anthocyanin supplements with every meal would provide higher plasma concentrations for some anthocyanins and their metabolites than the once or twice-a-day dose regimens.

Chronic subdural haematoma in antithrombotic cohorts: characteristics, surgical outcomes, and recurrence.

Objective: With the continuing increase of the aged population, neurosurgeons face increasing numbers of chronic subdural haematoma (CSDH) patients using antithrombotic (AT) drugs, i.e., anticoagulants (ACs) and antiplatelets (APs). However, there are few case reports that address this cohort and their outcomes. Here, a retrospective analysis of CSDH patients on AT therapies was performed to investigate their clinical characteristics, surgical outcomes, and postoperative recurrence.Methods: We analysed 546 CSDH patients who underwent surgery at the Subei People's Hospital of Jiangsu province from January 2014 to December 2017. The patients were divided into groups based on their history of preceding AT treatments as well as recurrence. The clinical data, surgical outcomes, and recurrence were collected for further analysis.Results: A total of 124 patients (22.7%) were receiving AT therapy, including 43 patients (7.9%) taking ACs and 81 patients (14.8%) taking APs. AT cohorts exhibited significantly higher non-traumatic CSDH, more serious pre-illness status, and larger haematoma volume, compared with the control patients. The haematoma clearance rate, duration of YL-1 needle, complications, and functional outcomes did not differ after novel YL-1 needle drainage, whereas a higher recurrence, mortality, and prolonged length of stay were observed in the AT group. Multivariate regression of postoperative recurrence within 3 months revealed that preoperative consciousness disorders, AC therapy, haematoma volume, and operative complications were significant predictive factors of CSDH recurrence. However, AP therapy was not associated with recurrence.Conclusions: The use of ATs causes large haematoma volumes that aggravate the severity in CSDH patients and is more prevalent among non-traumatic patients. AC therapy was a risk factor for CSDH recurrence, whereas AP therapy was not.

Long-term impact of dry eye symptoms on vision-related quality of life after phacoemulsification surgery.

PURPOSE: To observe the long-term changes in dry eye symptoms and vision-related quality of life in age-related cataract patients after phacoemulsification. METHODS: A total of 101 cataract patients after phacoemulsification combined with IOL implantation (Ph-IOL) in one eye were enrolled. Visual acuity, tear film breakup time (BUT), and Schirmer test 1 (ST1) were measured before and 1, 3, and 6 months after surgery. Ocular Surface Disease Index (OSDI) scores were used to evaluate the severity of dry eye symptoms. Utility values were assessed by the time trade-off (TTO), standard gamble for death (SGD), standard gamble for blindness (SGB) and rating scale (RS). RESULTS: The average LogMAR visual acuity in the operated eye was 1.35 ± 0.50 and increased rapidly after Ph-IOL, approaching a peak at 3 months (0.26 ± 0.15). The BUT and ST1 results decreased abruptly 1 month after surgery and gradually recovered until 6 months. OSDI scores increased significantly after surgery and gradually decreased until 6 months. Utility values evaluated by TTO, SGD, SGB and RS before surgery were 0.67 ± 0.19, 0.75 ± 0.15, 0.67 ± 0.20 and 0.2 ± 0.18, respectively, and increased to 0.91 ± 0.06, 0.98 ± 0.04, 0.92 ± 0.52 and 0.91 ± 0.06, 6 months after. Utility values measured with TTO, SGB or RS correlated significantly (P < 0.05) with visual acuity and OSDI scores pre- and postoperatively. CONCLUSIONS: Dry eye symptoms persist more than 3 months after Ph-IOL. Utility values were negatively influenced by dry eye symptoms.

COMPARISON OF RECENTLY USED PHACOEMULSIFICATION SYSTEMS USING A HEALTH TECHNOLOGY ASSESSMENT METHOD.

OBJECTIVES: To compare the recently used phacoemulsification systems using a health technology assessment (HTA) model. METHODS: A self-administered questionnaire, which included questions to gauge on the opinions of the recently used phacoemulsification systems, was distributed to the chief cataract surgeons in the departments of ophthalmology of eighteen tertiary hospitals in Shanghai, China. A series of senile cataract patients undergoing phacoemulsification surgery were enrolled in the study. The surgical results and the average costs related to their surgeries were all recorded and compared for the recently used phacoemulsification systems. RESULTS: The four phacoemulsification systems currently used in Shanghai are the Infiniti Vision, Centurion Vision, WhiteStar Signature, and Stellaris Vision Enhancement systems. All of the doctors confirmed that the systems they used would help cataract patients recover vision. A total of 150 cataract patients who underwent phacoemulsification surgery were enrolled in the present study. A significant difference was found among the four groups in cumulative dissipated energy, with the lowest value found in the Centurion group. No serious complications were observed and a positive trend in visual acuity was found in all four groups after cataract surgery. The highest total cost of surgery was associated with procedures conducted using the Centurion Vision system, and significant differences between systems were mainly because of the cost of the consumables used in the different surgeries. CONCLUSIONS: This HTA comparison of four recently used phacoemulsification systems found that each of system offers a satisfactory vision recovery outcome, but differs in surgical efficacy and costs.

The Growth Hormone Secretagogue Hexarelin Protects Rat Cardiomyocytes From in vivo Ischemia/Reperfusion Injury Through Interleukin-1 Signaling Pathway.

Hexarelin, a synthetic growth hormone-releasing peptide, has been proven to possess cardioprotective actions through its binding to the growth hormone secretagogue receptor (GHSR) 1a and the non-GHSR receptor CD36. However, its effect on myocardial ischemia/reperfusion (I/R) injury has not been fully clarified in vivo. We aimed to determine whether hexarelin treatment could protect cardiomyocytes from I/R injury and to examine the underlying mechanisms. In vivo hearts of male SD rats underwent 30 minutes of ischemia by left coronary artery ligation followed by reperfusion. The rats were then treated subcutaneously twice daily with hexarelin [100 µg/kg·day], ghrelin [400 µg/ kg·day], or saline for 7 days. Echocardiography, malondialdehyde detection, and histochemical staining were performed after treatment. In addition, Western blot was used to examine the expression levels of IL-1ß, IL-1Ra, and IL-1RI. Our study showed that hexarelin treatment improved cardiac systolic function, decreased malondialdehyde production, and increased the number of surviving cardiomyocytes. The beneficial effects of hexarelin treatment were slightly superior to those of equimolar ghrelin treatment. We meanwhile confirmed that hexarelin induced down-regulation of IL-1ß expression and up-regulation of IL-1Ra expression in I/R myocardium, which could be neutralized by the GHSR antagonist [D-Lys3]-growth hormone releasing peptide-6 ([D-Lys3]-GHRP-6). These findings suggest that hexarelin protects in vivo cardiomyocytes from I/R injury partly by modification of the IL-1 signaling pathway through the activation of cardiac GHSR1a receptors.

Cost-Utility Analyses of Cataract Surgery in Advanced Age-Related Macular Degeneration.

PURPOSE: To explore the cost-utility of cataract surgery in patients with advanced age-related macular degeneration (AMD). METHODS: Patients who were diagnosed as having and treated for age-related cataract and with a history of advanced AMD at the Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, were included in the study. All of the participants underwent successful phacoemulsification with foldable posterior chamber intraocular lens implantation under retrobulbar anesthesia. Best-corrected visual acuity (BCVA) and utility value elicited by time trade-off method from patients at 3-month postoperative time were compared with those before surgery. Quality-adjusted life years (QALYs) gained in a lifetime were calculated at a 3% annual discounted rate. Costs per QALY gained were calculated using the bootstrap method, and probabilities of being cost-effective were presented using a cost-effectiveness acceptability curve. Sensitivity analyses were performed to test the robustness of the results. RESULTS: Mean logarithm of the minimum angle of resolution BCVA in the operated eye increased from 1.37 ± 0.5 (Snellen, 20/469) to 0.98 ± 0.25 (Snellen, 20/191) (p < 0.001); BCVA in the weighted average from both eyes (=75% better eye + 25% worse eye) was changed from 1.13 ± 0.22 (Snellen, 20/270) to 0.96 ± 0.17 (Snellen, 20/182) (p < 0.001). Utility values from both patients and doctors increased significantly after surgery (p < 0.001 and p = 0.007). Patients gained 1.17 QALYs by cataract surgery in their lifetime. The cost per QALY was 8835 Chinese yuan (CNY) (1400 U.S. dollars [USD]). It is cost-effective at the threshold of 115,062 CNY (18,235 USD) per QALY in China recommended by the World Health Organization. The cost per QALY varied from 7045 CNY (1116 USD) to 94,178 CNY (14,925 USD) in sensitivity analyses. CONCLUSIONS: Visual acuity and quality of life assessed by utility value improved significantly after surgery. Cataract surgery was a cost-effective intervention for patients with coexistent AMD.

Mediastinal actinomycosis masquerading as a mass: a case of progressive dysphagia in an immunocompromised patient.

Actinomycosis is a rare endogenous infection characterised by indolent progression, contiguous spreading, abscess formation and draining sinuses. Here, we present a case of Schaalia odontolytica causing a mediastinal abscess that is unique in its acuity and location. Our patient presented with worsening dysphagia, and CT of her chest revealed a new mass in the posterior mediastinum displacing the oesophagus. Oesophagram revealed mild motility disorder, but no masses or ulcers within the oesophagus. Oesophagogastroduodenoscopy with endoscopic ultrasound revealed extrinsic compression of the oesophagus. Fine-needle aspiration of the mass yielded purulent fluid, which was cultured. A single colony of S. odontolytica was isolated. Initially, medical treatment was favoured, but as she developed worsening dysphagia, the abscess was drained. She continued on long-term antibiotic therapy after drainage and had complete resolution of the abscess at 1 year.

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.

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.

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.

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.

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.

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.

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.

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.