Comparative associations of MASLD and MAFLD with the presence and severity of coronary artery calcification.

We aimed to compare the associations of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) with coronary artery calcification (CAC). Patients who simultaneously underwent ultrasonography to diagnose hepatic steatosis and cardiac computed tomography to detect CAC were included. The presence and severity of CAC were defined with CAC-score thresholds of > 0 and > 300, respectively, and patients were divided into the following groups: no MASLD or MAFLD (reference), MASLD-only, MAFLD-only, and overlapping groups. Overall, 1,060/2,773 (38.2%) patients had CAC, of which 196 (18.5%) had severe CAC. The MASLD and MAFLD prevalence rates were 32.6% and 45.2%, respectively, with an overlap of 30.7%. In an ASCVD risk score-adjusted model, both MASLD (adjusted odd ratios [aOR], 1.21; 95% confidence interval [CI], 1.02-1.44; p = 0.033) and MAFLD (aOR 1.20; 95% CI 1.01-1.42, p = 0.034) were associated with CAC, whereas only MASLD (aOR 1.38; 95% CI 1.01-1.89, p = 0.041) was associated with severe CAC. Compared to the reference group, the overlapping group showed an association with CAC (aOR 1.22; 95% CI 1.01-1.47; p = 0.038); however, the MASLD and MAFLD subgroups did not differ in their association with CAC. MASLD may predict a higher risk of ASCVD more effectively than MAFLD.

Calcium-permeable AMPA receptors govern PV neuron feature selectivity.

The brain helps us survive by forming internal representations of the external world1,2. Excitatory cortical neurons are often precisely tuned to specific external stimuli3,4. However, inhibitory neurons, such as parvalbumin-positive (PV) interneurons, are generally less selective5. PV interneurons differ from excitatory neurons in their neurotransmitter receptor subtypes, including AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors (AMPARs)6,7. Excitatory neurons express calcium-impermeable AMPARs that contain the GluA2 subunit (encoded by GRIA2), whereas PV interneurons express receptors that lack the GluA2 subunit and are calcium-permeable (CP-AMPARs). Here we demonstrate a causal relationship between CP-AMPAR expression and the low feature selectivity of PV interneurons. We find low expression stoichiometry of GRIA2 mRNA relative to other subunits in PV interneurons that is conserved across ferrets, rodents, marmosets and humans, and causes abundant CP-AMPAR expression. Replacing CP-AMPARs in PV interneurons with calcium-impermeable AMPARs increased their orientation selectivity in the visual cortex. Manipulations to induce sparse CP-AMPAR expression demonstrated that this increase was cell-autonomous and could occur with changes beyond development. Notably, excitatory-PV interneuron connectivity rates and unitary synaptic strength were unaltered by CP-AMPAR removal, which suggested that the selectivity of PV interneurons can be altered without markedly changing connectivity. In Gria2-knockout mice, in which all AMPARs are calcium-permeable, excitatory neurons showed significantly degraded orientation selectivity, which suggested that CP-AMPARs are sufficient to drive lower selectivity regardless of cell type. Moreover, hippocampal PV interneurons, which usually exhibit low spatial tuning, became more spatially selective after removing CP-AMPARs, which indicated that CP-AMPARs suppress the feature selectivity of PV interneurons independent of modality. These results reveal a new role of CP-AMPARs in maintaining low-selectivity sensory representation in PV interneurons and implicate a conserved molecular mechanism that distinguishes this cell type in the neocortex.

Distorted time perception in patients with neurocognitive impairment.

Background: Time perception is known to be distorted in patients with neuropsychiatric disorders. Therefore, this study aims to investigate the correlation between cognitive decline and time distortion by examining time perception in participants with neurocognitive impairment (Alzheimer's disease [AD], vascular dementia [VD], and Parkinson's disease dementia [PDD]) compared to those with subjective cognitive impairment (SCI). Methods: Overall, 569 participants with cognitive decline complaints between 2013 and 2022 were investigated. Participants were subjected to a verbal estimation task, time production task, time comparison task, and neuropsychological assessments. Results: Time perception abilities were distorted in patients with neurocognitive impairment compared to those with SCI. Despite similar educational backgrounds, the vascular cognitive impairment (VCI)/VD group demonstrated the lowest MMSE scores (22.4 ± 4.2, p-value <0.001) and larger time-estimation errors. Patients with VCI/VD significantly underestimated time in the 35-s (19.6 ± 12.6s) and 60-s (28.7 ± 19.9s) tasks. In the time production task, patients with VCI/VD produced shorter times in their 15-s (12.7 ± 4.3; p-value = 0.001), 30-s (23.6 ± 8.3; p value < 0.001), and 60-s (43.8 ± 18.9; p-value <0.001) trials. In the time comparison task, the VCI/VD group had significantly fewer correct answers than that in the SCI groups (6.0 ± 1.3 vs. 7.1 ± 0.9, p-value <0.001). Correlation analysis revealed that multiple cognitive functions are involved in the time perception tasks. Conclusions: Patients with VCI/VD had the poorest time perception. These findings may provide a modest contribution to understanding the underlying pathophysiology and psychological connections related to temporal abilities in time perception.

A Rare Case of X-Linked Four-Way Philadelphia Chromosome Translocation with Therapeutic Challenges and Clonal Evolution.

BACKGROUND: Chronic myeloid leukemia (CML), a myeloproliferative neoplasm defined by the BCR::ABL1 fusion gene arising from the Philadelphia chromosome (Ph) translocation t(9:22)(q34;q11), exhibits diverse clinical courses often influenced by additional chromosomal aberrations (ACAs). This report presents a case of CML har-boring a novel four-way Ph translocation involving the X chromosome, offering insights into the interplay between complex karyotypes and treatment response and emphasizing the need for further research into the role of ACAs in CML management. METHODS: A 42-year-old man diagnosed with CML in the accelerated phase presented a novel four-way Ph translocation involving chromosomes X, 5, 9, and 22: 46,Y,t(X;5;9;22)(q26;q15;q34;q11.2). Despite achieving a major molecular response initially with imatinib and nilotinib, BCR::ABL1 levels (international scale) increased up to 24.0%, which prompted the use of second-line nilotinib. RESULTS: Follow-up bone marrow (BM) studies revealed clonal evolution with trisomy 8 and an unclassified ABL1 mutation (E292V), potentially contributing to resistance. Though a transient major molecular response (MMR) occurred after a switch to third-line dasatinib, this change failed to achieve a deep molecular response, and BCR-ABL1 levels were elevated above the MMR. CONCLUSIONS: This case highlights the challenge of ACAs impacting CML treatment response and prognosis. Limited knowledge exists on complex Ph translocations involving the X chromosome, but this report contributes data for further research. Understanding ACA effects on therapeutic response and prognosis requires a detailed study of such complex chromosomal aberrations.

Local Ablation for Hepatocellular Carcinoma: 2024 Expert Consensus-Based Practical Recommendations of the Korean Liver Cancer Association.

Local ablation for hepatocellular carcinoma, a non-surgical option that directly targets and destroys tumor cells, has advanced significantly since the 1990s. Therapies with different energy sources, such as radiofrequency ablation, microwave ablation, and cryoablation, employ different mechanisms to induce tumor necrosis. The precision, safety, and effectiveness of these therapies have increased with advances in guiding technologies and device improvements. Consequently, local ablation has become the first-line treatment for early-stage hepatocellular carcinoma. The lack of organized evidence and expert opinions regarding patient selection, preprocedure preparation, procedural methods, swift post-treatment evaluation, and follow-up has resulted in clinicians following varied practices. Therefore, an expert consensus-based practical recommendation for local ablation was developed by a group of experts in radiology and hepatology from the Research Committee of the Korean Liver Cancer Association in collaboration with the Korean Society of Image-Guided Tumor Ablation to provide useful information and guidance for performing local ablation and for the pre- and post-treatment management of patients.

The Impact of Pinus koraiensis Leaf Extract Consumption on Postprandial ApoB100 and Lipid Metabolism: A Randomized, Double-Blind, Placebo-Controlled Trial in Healthy Participants Subjected to an Oral High-Fat Challenge.

Pinus koraiensis (PK) leaf extract, derived from Korean pine byproducts, holds promise for alleviating postprandial hyperlipidemia. In this study, we investigated the potential of PK leaf extract for modulating postprandial hyperlipidemia in adults with normal or borderline fasting triglyceride levels. In a randomized, double-blind, parallel design, 70 subjects were randomly assigned to either the placebo or PK group for 4 weeks. After 4 weeks of consuming PK leaf extract, the results indicated a trend toward decreased serum apolipoprotein B-100 (ApoB100) levels 2 h after a high-fat challenge. Furthermore, significant improvements were observed in the incremental area under the curve (iAUC) at 0-4 h and 2-4 h compared to baseline, particularly among individuals with a higher body weight (>61.35 kg) and daily caloric intake (>1276.5 kcal). Based on these findings, PK leaf extract may have beneficial effects on postprandial lipoprotein metabolism, especially among individuals with a relatively high body weight and caloric intake.

The Effect of Organic Vegetable Mixed Juice on Blood Circulation and Intestine Flora: Randomized, Double-Blinded, Placebo-Controlled Clinical Trial.

Epidemiological evidence suggests that fruit and vegetable intake significantly positively affects cardiovascular health. Since vegetable juice is more accessible than raw vegetables, it attracts attention as a health functional food for circulatory diseases. Therefore, this study measured blood lipids, antioxidants, blood circulation indicators, and changes in the microbiome to confirm the effect of organic vegetable mixed juice (OVJ) on improving blood circulation. This 4-week, randomized, double-blinded, placebo-controlled study involved adult men and women with borderline total cholesterol (TC) and low-density lipoprotein (LDL) levels. As a result, blood lipid profile indicators, such as TC, triglycerides, LDL cholesterol, and apolipoprotein B, decreased (p < 0.05) in the OVJ group compared with those in the placebo group. Additionally, the antioxidant biomarker superoxide dismutase increased (p < 0.05). In contrast, systolic and diastolic blood viscosities, as blood circulation-related biomarkers, decreased (p < 0.05) in the OVJ group compared with those in the placebo group. After the intervention, a fecal microbiome analysis confirmed differences due to changes in the intestinal microbiome composition between the OVJ and placebo groups. In conclusion, our research results confirmed that consuming OVJ improves blood circulation by affecting the blood lipid profile, antioxidant enzymes, and microbiome changes.

The Effects of Lilium lancifolium Thunb. on the Alleviation of Joint Pain: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Arthritis is mainly a geriatric disease that causes joint pain and lowers the quality of life. This clinical trial was performed to evaluate the efficacy of Lilium lancifolium Thunb. (HY-LL) in alleviating joint pain. Six candidate anti-inflammatory components including regaloside A were identified in HY-LL using HPLC analysis. All participants were assigned to the HY-LL or the placebo group and took tablets twice a day for 12 weeks. As a result, pain VAS and K-WOMAC total scores significantly decreased after 12 weeks compared to the baseline in the HY-LL group, with a statistically significant difference between the two groups (p = 0.043, 0.043). The K-WOMAC sub-scores for pain and function showed a statistically significant improvement in the HY-LL group compared to the placebo group (p = 0.023, 0.047). Furthermore, the participants' overall quality of life improved after 12 weeks of HY-LL consumption (p = 0.024). However, no significant differences were observed in the blood biomarkers. Therefore, this study demonstrated the positive effect of 12 weeks of HY-LL consumption on joint pain and quality of life.

Real-world safety and effectiveness of lenvatinib in unresectable hepatocellular carcinoma in Korea: post-marketing study.

Aim: This post-marketing surveillance study evaluated the safety and effectiveness of lenvatinib as first-line treatment for unresectable hepatocellular carcinoma in Korea.Materials & methods: Adverse drug reactions (ADRs) and other safety and effectiveness end points were assessed in patients who initiated lenvatinib according to the approved label in republic of Korea.Results: Among 658 lenvatinib-treated patients, ADRs were reported in 57.8%; ADRs grade ≥3 in 13.5%. The most common grade ≥3 ADRs were asthenia (1.2%) and hepatic encephalopathy (1.2%). Physician-reported tumor responses (n = 511) were complete (1.0%) or partial (12.9%) response and stable (45.2%) or progressive disease (40.9%); objective response rates were higher with longer lenvatinib treatment duration (p < 0.001).Conclusion: Lenvatinib was generally well tolerated and effective in real-world clinical practice in Korea.Clinical trial registration: ClinicalTrials.gov NCT05225207.

[Box: see text].

Volumizing and Cogged Threads for Nose Augmentation.

BACKGROUND: Nose augmentation using nonsurgical methods, including volumizing and cogged threads, has gained popularity due to its minimally invasive nature, shorter recovery times, and reduced risks compared to traditional rhinoplasty. However, there is limited literature on the use of these techniques in the Asian population. AIMS: This study aims to present two successful cases of nose augmentation using volumizing and cogged threads, providing evidence of their effectiveness and demonstrating the insertion techniques through a supplementary video. PATIENTS/METHODS: Two female patients (aged 26 and 33) underwent nonsurgical nose augmentation. The first patient received volumizing threads to enhance nasal contour, while the second patient received cogged threads to refine the nasal tip and alar base. Both procedures were performed using polydioxanone (PDO) threads, with follow-ups conducted to assess the outcomes. RESULTS: Both patients exhibited significant improvement in nasal contour and projection, with outcomes maintained for up to 8 months post-procedure. The patients reported high satisfaction with the aesthetic results, and no complications were observed during the follow-up period. CONCLUSIONS: Volumizing and cogged threads offer a promising nonsurgical alternative for nose augmentation, particularly in patients seeking minimal invasiveness and natural-looking results. While the initial outcomes are positive, further research is needed to evaluate the long-term safety and effectiveness of these techniques, especially in the Asian demographic.

Efficacy of PARP inhibitor therapy after targeted BRAF/MEK failure in advanced melanoma.

Modern advancements in targeted therapy and immunotherapy have significantly improved survival outcomes for advanced melanoma; however, there remains a need for novel approaches to overcome disease progression and treatment resistance. In recent years, PARPi therapy has shown great promise both as a single regimen and in combination with other therapeutics in melanoma. Here, we describe three unique cases of advanced BRAF V600 mutated melanoma that progressed on targeted BRAF/MEK agents that subsequently exhibited partial to near-complete responses to combinatory PARPi and BRAF/MEK inhibitors. This highlights both a potential synergy underlying this combinatory approach and its efficacy as a treatment option for patients with advanced melanoma refractory to targeted and/or immunotherapies. Prospective clinical trials are needed to explore this synergic effect in larger melanoma cohorts to investigate this combination for treating refractory advanced melanoma.

Rescue therapy of early neurological deterioration in lacunar stroke.

BACKGROUND: Early neurological deterioration (END) occurs in many patients with acute ischemic stroke due to a variety of causes. Although pharmacologically induced hypertension (PIH) and anticoagulants have been investigated in several clinical trials for the treatment of END, the efficacy and safety of these treatments remain unclear. Here, we investigated whether PIH or anticoagulation is better as a rescue therapy for the progression of END in patients with lacunar stroke. METHODS: This study included patients with lacunar stroke who received rescue therapy with END within 3 days of symptom onset between April 2014 and August 2021. In the PIH group, phenylephrine was administered intravenously for 24 h and slowly tapered when symptoms improved or after 5 days of PIH. In the anticoagulation group, argatroban was administered continuously intravenously for 2 days and twice daily for next 5 days. We compared END recovery, defined as improvement in NIHSS from baseline, excellent outcomes (0 or 1 mRS at 3 months), and safety profile. RESULTS: Among the 4818 patients with the lacunar stroke, END occurred in 147 patients. Seventy-nine patients with END received PIH (46.9%) and 68 patients (46.3%) received anticoagulation therapy. There was no significant difference in age (P = 0.82) and sex (P = 0.87) between the two groups. Compared to the anticoagulation group, the PIH group had a higher incidence of END recovery (77.2% vs. 51.5%, P < 0.01) and excellent outcomes (34.2% vs. 16.2%, P = 0.04). PIH was associated with END (HR 2.49; 95% CI 1.06-5.81, P = 0.04). PIH remained associated with END recovery (adjusted HR 3.91; 95% CI 1.19-12.90, P = 0.02). Safety outcomes, like hemorrhagic conversion and mortality, were not significantly different between the two groups. CONCLUSIONS: As a rescue therapy for the progression of END in lacunar stroke patients, PIH with phenylephrine was more effective with similar safety compared to anticoagulation with argatroban.

Sphingosine-1-Phosphate-Cathelicidin Axis Plays a Pivotal Role in the Development of Cutaneous Squamous Cell Carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is a common skin cancer caused by mutagenesis resulting from excess UVR or other types of oxidative stress. These stressors also upregulate the production of a cutaneous innate immune element, cathelicidin antimicrobial peptide (CAMP), through endoplasmic reticulum stress-initiated, sphingosine-1-phosphate (S1P) signaling pathway. Although CAMP has beneficial antimicrobial activities, it also can be proinflammatory and procarcinogenic. We addressed whether and how S1P-induced CAMP production leads to cSCC development. Our study demonstrated that (i) CAMP expression is increased in cSCC cells and skin from patients with cSCC; (ii) S1P levels are elevated in cSCC cells, whereas inhibition of S1P production attenuates CAMP-stimulated cSCC growth; (iii) exogenous CAMP stimulates cSCC but not normal human keratinocyte growth; (iv) blockade of FPRL1 protein, a CAMP receptor, attenuates cSCC growth as well as the growth and invasion of cSCC cells mediated by CAMP into an extracellular matrix-containing fibroblast substrate; (v) FOXP3+ regulatory T-cell (which decreases antitumor immunity) levels increase in cSCC skin; and (vi) CAMP induces endoplasmic reticulum stress in cSCC cells. Together, the endoplasmic reticulum stress-S1P-CAMP axis forms a vicious circle, creating a favorable environment for cSCC development, that is, cSCC growth and invasion impede anticancer immunity.

Evaluating the impact of a year-long external mentorship pilot program in classical hematology.

ABSTRACT: Effective mentorship is a pivotal factor in shaping the career trajectory of trainees interested in classical hematology (CH), which is of critical importance due to the anticipated decline in the CH workforce. However, there is a lack of mentorship opportunities within CH compared with medical oncology. To address this need, a year-long external mentorship program was implemented through the American Society of Hematology Medical Educators Institute. Thirty-five hematology/oncology fellows interested in CH and 34 academically productive faculty mentors from different institutions across North America were paired in a meticulous process that considered individual interests, experiences, and background. Pairs were expected to meet virtually once a month. Participation in a scholarly project was optional. A mixed-methods sequential explanatory design was used to evaluate the program using mentee and mentor surveys, a mentee interview, and a mentee focus group. Thirty-three mentee-mentor pairs (94.2%) completed the program. Sixty-three percent of mentee respondents worked on a scholarly project with their mentor; several mentees earned publications, grants, and awards. Mentee perception that their assigned mentor was a good match was associated with a perceived positive impact on confidence (P = .0423), career development (P = .0423), and professional identity (P = .0302). Furthermore, 23 mentees (66%) accepted CH faculty positions after fellowship. All mentor respondents believed that this program would increase retention in CH. This mentorship program demonstrates a productive, beneficial way of connecting mentees and mentors from different institutions to improve the careers of CH trainees, with the ultimate goal of increasing retention in CH.

Postoperative Calcaneocuboid Joint Subluxation and Midtarsal Joint Changes in Pediatric Idiopathic Flexible Flatfoot Treated With Calcaneal Lengthening Osteotomy: A Midterm Follow-up Study.

BACKGROUND: Calcaneal lengthening osteotomy (CLO) is one of the main surgical options for treatment of pediatric idiopathic flexible flatfoot (FFF). Reportedly, calcaneocuboid (CC) joint subluxation occurs after CLO; however, its effect on the midfoot remains unclear. This study aimed to investigate the radiologic midterm results after CLO treatment in pediatric idiopathic FFF. METHODS: We evaluated 23 pediatric patients with idiopathic FFF aged ≥8 years, who underwent CLO from 1999 to 2017 owing to moderate to severe flatfoot deformity (assessed by visual inspection). Patients aged between 8 and 14 years were included (mean follow-up: 6.3 years; range, 3.1-11.4 years). Anteroposterior and lateral weightbearing foot radiographs were assessed for radiologic parameters preoperatively and at the 3-month, 1-year, and final follow-ups postoperatively. RESULTS: All patients had immediate postoperative radiologic correction of the flatfoot deformity, and these improvements were maintained until the final follow-up. The mean allograft length inserted was 9 (range, 8-10) mm. There was increased CC joint subluxation after CLO, but it improved continuously until the final follow-up. A CC joint spur was newly noted in 1 case. There were 24 cases (24/39, 61.5%) of talonavicular (TN) joint spurs at the final follow-up, but 19 of these were already present on the preoperative radiographs (19/24, 79.2%). Further, the new-onset TN joint spurs were not associated with preoperative clinicoradiologic factors. CONCLUSION: In pediatric patients with idiopathic FFF receiving CLO treatment, preoperative radiologic angles improved. CC joint subluxation increased after surgery; however, it gradually reduced without evidence of CC joint arthritic changes over the time period studied in this cohort.

Temporal trends and long-term outcomes of radiofrequency ablation for hepatocellular carcinoma within the Milan criteria.

No study has analysed the temporal trends of the long-term results and clinical characteristics of patients with hepatocellular carcinoma (HCC) treated using radiofrequency ablation (RFA). Therefore, we examined temporal trends of characteristics of patients and treatment-naïve HCCs within the Milan criteria treated by RFA over 20 years. We retrospectively analysed 1099 patients with HCC within the Milan criteria treated with percutaneous RFA from January 2000 to December 2019. The overall survival (OS), recurrence-free survival (RFS), and factors affecting survival and local tumor progression were analysed using the Kaplan‒Meier method and Cox proportional hazards model. A trend test was performed to analyse the changing trends in participants and treatment outcomes. The overall and RFS of patients improved during the later period. In addition, viral hepatitis-related HCC incidence decreased, whereas that of alcohol- or non-alcoholic fatty liver disease-related HCC increased from the earlier to the later period (P for trend < 0.001). HBV antiviral therapy was increased and improved OS and RFS in patients treated using RFA. The outcomes after RFA over a 20-year period improved due to changes over time in target tumors and patients. The results could be useful for selecting patients who will benefit from RFA.

Effectiveness and safety of steamed ginger extract on mild osteoarthritis: a randomized, double-blind, placebo-controlled clinical trial.

The purpose of this study was to evaluate the efficacy and safety of steamed ginger extract (GGE03) in subjects with mild knee osteoarthritis (OA). In total, 100 subjects were randomly assigned (1 : 1) to the GGE03 (0.48 g day-1 as GGE03) or placebo (0 g day-1 as GGE03) group and administered 1.6 g of the product for 12 weeks. Biomarkers were measured before and after intervention. At the efficacy endpoint, pain visual analog scale (VAS) Korean-Western Ontario and McMaster University Osteoarthritis Index (K-WOMAC; total scores, sub-scores) and patient global assessment (PGA) were found to be decreased in a statistically significantly manner in the GGE03 group compared to the placebo group. No significant changes were observed in any safety endpoint. These results suggest that GGE03 intake is useful as a functional food because it has beneficial effects in terms of improving joint pain as well as managing or preventing knee OA without side effects.

Stroke Measures Analysis of pRognostic Testing-Mortality nomogram predicts long-term mortality after ischemic stroke.

BACKGROUND: Predicting long-term mortality is essential for understanding prognosis and guiding treatment decisions in patients with ischemic stroke. Therefore, this study aimed to develop and validate the method for predicting 1- and 5-year mortality after ischemic stroke. METHODS: We used data from the linked dataset comprising the administrative claims database of the Health Insurance Review and Assessment Service and the Clinical Research Center for Stroke registry data for patients with acute stroke within 7 days of onset. The outcome was all-cause mortality following ischemic stroke. Clinical variables linked to long-term mortality following ischemic stroke were determined. A nomogram was constructed based on the Cox's regression analysis. The performance of the risk prediction model was evaluated using the Harrell's C-index. RESULTS: This study included 42,207 ischemic stroke patients, with a mean age of 66.6 years and 59.2% being male. The patients were randomly divided into training (n = 29,916) and validation (n = 12,291) groups. Variables correlated with long-term mortality in patients with ischemic stroke, including age, sex, body mass index, stroke severity, stroke mechanisms, onset-to-door time, pre-stroke dependency, history of stroke, diabetes mellitus, hypertension, coronary artery disease, chronic kidney disease, cancer, smoking, fasting glucose level, previous statin therapy, thrombolytic therapy, such as intravenous thrombolysis and endovascular recanalization therapy, medications, and discharge modified Rankin Scale were identified as predictors. We developed a predictive system named Stroke Measures Analysis of pRognostic Testing-Mortality (SMART-M) by constructing a nomogram using the identified features. The C-statistics of the nomogram in the developing and validation groups were 0.806 (95% confidence interval (CI), 0.802-0.812) and 0.803 (95% CI, 0.795-0.811), respectively. CONCLUSION: The SMART-M method demonstrated good performance in predicting long-term mortality in ischemic stroke patients. This method may help physicians and family members understand the long-term outcomes and guide the appropriate decision-making process.

Evaluation of Chronic Pancreatitis Prognosis Score in an American Cohort.

INTRODUCTION: Chronic Pancreatitis Prognosis Score (COPPS) was developed to discriminate disease severity and predict risk for future hospitalizations. In this cohort study, we evaluated if COPPS predicts the likelihood of hospitalization(s) in an American cohort. METHODS: The Chronic Pancreatitis, Diabetes, and Pancreatic Cancer consortium provided data and serum from subjects with chronic pancreatitis (N = 279). COPPS was calculated with baseline data and stratified by severity (low, moderate, and high). Primary endpoints included number and duration of hospitalizations during 12-month follow-up. RESULTS: The mean ± SD COPPS was 8.4 ± 1.6. COPPS correlated with all primary outcomes: hospitalizations for any reason (number: r = 0.15, P = 0.01; duration: r = 0.16, P = 0.01) and pancreas-related hospitalizations (number: r = 0.15, P = 0.02; duration: r = 0.13, P = 0.04). The severity distribution was 13.3% low, 66.0% moderate, and 20.8% high. 37.6% of subjects had ≥1 hospitalization(s) for any reason; 32.2% had ≥1 pancreas-related hospitalizations. All primary outcomes were significantly different between severity groups: hospitalizations for any reason (number, P = 0.004; duration, P = 0.007) and pancreas-related hospitalizations (number, P = 0.02; duration, P = 0.04). The prevalence of continued drinking at follow-up ( P = 0.04) was higher in the low and moderate groups. The prevalence of anxiety at enrollment ( P = 0.02) and follow-up ( P < 0.05) was higher in the moderate and high groups. DISCUSSION: Statistically, COPPS significantly correlated with hospitalization outcomes, but the correlations were weaker than in previous studies, which may be related to the outpatient nature of the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies cohort and lower prevalence of high severity disease. Studies in other prospective cohorts are needed to understand the full utility of COPPS as a potential tool for clinical risk assessment and intervention.

The Mutational and Microenvironmental Landscape of Cutaneous Squamous Cell Carcinoma: A Review.

Cutaneous squamous cell carcinoma (cSCC) manifests through the complex interactions of UV-induced DNA damage, genetic mutations, and alterations in the tumor microenvironment. A high mutational burden is present in cSCC, as well as both cSCC precursors and normal skin, making driver genes difficult to differentiate. Despite this, several key driver genes have been identified, including TP53, the NOTCH family, CDKN2A, PIK3CA, and EGFR. In addition to mutations, the tumor microenvironment and the manipulation and evasion of the immune system play a critical role in cSCC progression. Novel therapeutic approaches, such as immunotherapy and EGFR inhibitors, have been used to target these dysregulations, and have shown promise in treating advanced cSCC cases, emphasizing the need for targeted interventions considering both genetic and microenvironmental factors for improved patient outcomes.