Purpose: Metastatic rectal cancer (mRC) is a highly lethal and complex disease that demands a multidisciplinary treatment approach. However, the clinical effectiveness of radiotherapy (RT) for de novo mRC remains controversial and uncertain. Methods: This retrospective cohort study examined medical records from Kaohsiung Chang Gung Memorial Hospital for patients with histologically confirmed de novo mRC diagnosed between January 2015 and December 2020. All patients received standard systemic therapy and radical surgery when feasible. The primary outcome, overall survival (OS), was assessed using the Kaplan-Meier method. Multivariable analysis was performed using a Cox regression model. Results: Among 271 patients included in the analysis, 117 received RT and 154 did not. The median OS was significantly longer in the RT group compared with the non-RT group (27.8 months vs. 21.9 months; P=0.046). Multivariate analysis identified several independent predictors of OS: age ≥65 years (hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.26–2.27; P=0.001), primary tumor resection (HR, 2.62; 95% CI, 1.90–3.61; P<0.001), M1b or M1c disease (HR, 1.97; 95% CI, 1.44–2.69; P<0.001), and receipt of RT (HR, 1.41; 95% CI, 1.02–1.94; P=0.036). Conclusion RT significantly improves OS in patients with mRC, underscoring its role in treatment strategies. These findings support its inclusion in therapeutic protocols and highlight the need for larger, multicenter trials to confirm and extend these results.

Malignant gastric outlet obstruction (MGOO) occurs in 2% to 25% of patients with pancreatic ductal adenocarcinoma (PDAC) who do not undergo surgical intervention. Over the past decade, duodenal self-expandable metal stent (D-SEMS) has been widely used for MGOO and has demonstrated high technical (89.1% to 100%) and clinical (85.7% to 94.3%) success rates.Endoscopic ultrasonography-guided gastroenterostomy (EUS-GE) has emerged as a promising alternative with comparable technical (89.3% to 98.9%) and clinical (89.0% to 100%) success rates. Notably, EUS-GE reduces the 6-month reintervention rate by approximately 25% relative to D-SEMS in patients with MGOO, thus making it an increasingly popular treatment option. Despite its advantages, EUS-GE may not be suitable for patients with massive ascites, extensive peritoneal carcinomatosis, gastric linitis plastica, or an inaccessible small bowel. Moreover, EUSGE requires a longer procedure time and incurs higher overall costs, even when considering the increased reintervention rate associated with D-SEMS. While the risk of adverse events is similar between EUS-GE and D-SEMS, EUS-GE requires a higher level of operator expertise to ensure safety and may also require deeper levels of anesthesia than D-SEMS. Advancements in cancer therapy have prolonged survival in PDAC patients, but most do not require reintervention for MGOO, unlike those with other malignancies. Thus, EUS-GE may be suitable for patients with a longer life span who are willing to undergo deep anesthesia at a high-volume center with an experienced specialist. Given these considerations, more comprehensive studies are needed before EUS-GE can be recommended as a standard replacement for D-SEMS in the treatment of MGOO.

Introduction: Itch, an uncomfortable sensation leading to the urge to scratch, is often inadequately managed by conventional antihistamine drugs, which can be ineffective in certain pruritic conditions and cause undesirable side effects. Therefore, there is a need to identify new pharmacologically potent antipruritic compounds with fewer side effects. A synthetic curcuminoid analogue, 2,6-bis-(4-hydroxy-3-methoxybenzylidene)-cyclohexanone (BHMC), a derivative of curcumin - a bioactive compound found in turmeric - has demonstrated various pharmacological ac-tivities. Previous studies have shown that BHMC possesses antinociceptive and anti-inflammatory properties. This study aimed to investigate the antipruritic effects of BHMC in mice models of induced pruritus. Materials and Meth-ods: The pruritus in mice was induced using compound 48/80, substance P, histamine, and serotonin to establish an itch-induced mouse model. BHMC was administered intraperitoneally (i.p.) at doses of 0.1, 0.3, and 1.0 mg/kg. Results: BHMC significantly reduced pruriceptive responses in all models tested and notably inhibited compound 48/80 and substance P-induced mast cell degranulation in skin tissues. Conclusions: These findings suggest that BHMC inhibits pruriceptive responses in mice, likely through the inhibition of mast cell degranulation and/or direct antagonism of peripheral histamine and serotonin receptors. This may warrant further exploration of the antipruritic effect of BHMC in clinical trials for the betterment of animal and human health.

Objective:To analyze early improvements in clinical indicators among patients with pre-diabetes (pre-DM), type 2 diabetes mellitus (T2DM), and hypertension (HT) participating in the Chronic Disease Co-Care (CDCC) Pilot Scheme in the Hong Kong Special Administrative Region of the People′s Republic of China (HKSAR). Methods:This longitudinal study enrolled participants with pre-DM, T2DM, and HT who participated in the CDCC Pilot Scheme between November 2023 and May 2024. Baseline clinical data was collected. All participants were managed followed standardized protocols: family doctors issued prescriptions in accordance with the Hong Kong Reference Framework by the Health Bureau of the Government of the HKSAR, District Health Centre (DHC) and DHC Express provided health education, and personalized counseling by allied health professionals (nurses, optometrists, and dietitians). During the screening phase, screening costs, including consultations and related laboratory investigations, were fully covered by the Government of the HKSAR, while partial subsidies were available during the treatment phase. Participants were followed for 6 months. Primary outcomes were glycated hemoglobin A1c (HbA1c) for pre-DM and T2DM, and blood pressure for HT. Secondary outcomes included body mass index (BMI), triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and the Framingham model-based 10-year cardiovascular risk score. Changes in clinical indicators from baseline to 6 months were analyzed using a linear mixed model, with subgroup analyses by age, sex, and baseline Framingham 10-year cardiovascular disease risk score. Results:A total of 3 910 participants were included in the study, comprising 903 (23.1%) with pre-DM, 478 (12.2%) with T2DM, and 2 529 (64.7%) with HT. Pre-DM participants had an age of (61.4±7.0) years with 641 (71.0%) females; T2DM participants had an age of (60.4±7.4) years with 247 (51.7%) females; HT participants had an age of (60.8±7.9) years with 1 237 (48.9%) females. At 6 months, HbA1c levels declined in the pre-DM and T2DM groups by -0.09% (95% CI:-0.10%--0.07%) and -1.06% (95% CI:-1.21%--0.91%), respectively. In the HT group, systolic blood pressure decreased by 15.3 mmHg (1 mmHg=0.133 kPa) (95% CI:-16.0--14.6 mmHg) and diastolic blood pressure by 8.6 mmHg (95% CI:-9.0--8.1 mmHg). BMI decreased in the three groups, with the largest reduction in the T2DM group (-1.04 kg/m 2, 95% CI:-1.22--0.86 kg/m 2). TC, TG, and LDL-C levels decreased in the three groups (all P<0.05). Subgroup analysis revealed that among HT participants, individuals with a baseline Framingham 10-year cardiovascular disease risk of ≥20% experienced greater reductions in blood pressure compared to those with a risk <20% ( P<0.05). Additionally, male participants demonstrated significantly lower diastolic blood pressure than female participants ( P<0.05). Among participants with T2DM, males exhibited greater reductions in HbA1c levels than females, and participants aged 45-64 years showed significantly lower HbA1c levels compared to those aged 65 years and older (both P<0.05). Conclusions:In the early phase of the CDCC Pilot Scheme, glycemic, blood pressure, lipid, and BMI indicators improved among patients with pre-DM, T2DM, and HT. These effects were particularly pronounced in males and in individuals younger than 65 years of age.

INTRODUCTION: The COVID-19 pandemic has changed care provision models, with a rapid increase in the adoption of telemedicine to reduce in-person visits. Although there are many benefits to teledermatology, there are also factors that hinder its widespread adoption. We aimed to examine patients' perceptions of teledermatology to identify the barriers to its adoption. METHODS: A prospective study was conducted from 15 June to 14 August 2020. Patients were invited to complete a questionnaire in an outpatient dermatology clinic via direct approach by clinical staff or posters posted at the door of consultation rooms. RESULTS: Out of 2,276 clinic attendances, 997 survey responses (43.8%) were collected over a 3-month period. When asked if they would change their subsequent visit to teledermatology, 294 (29.5%) patients were keen, 166 (16.6%) were unsure and 537 (53.9%) declined. Significant factors for declining teledermatology were lack of prior exposure to videoconferencing ( P < 0.01) and lower educational level ( P = 0.019). Patients also raised concerns regarding the ability of teledermatology to address medical concerns (32.1%) and indicated a preference for face-to-face consultation (29.7%). CONCLUSION Factors that influence patients' decision to adopt teledermatology, such as concerns about its ability to address medical issues, lack of IT literacy or experience in teleconferencing, are modifiable. Targeted strategies such as careful patient selection, a dedicated teleconsultation workflow, and the use of a novel 'teledermatology patient journey' (including a clinic walkthrough at the first visit) and an intuitive audio-enabled user interface, may improve patient perceptions and adoption of teleconsultation service.
Humans ; COVID-19/epidemiology* ; Dermatology/methods* ; Telemedicine ; Male ; Female ; Prospective Studies ; Middle Aged ; Adult ; Surveys and Questionnaires ; SARS-CoV-2 ; Aged ; Perception ; Young Adult ; Pandemics ; Skin Diseases/diagnosis* ; Videoconferencing

Background/Aims: Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population. Methods: This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019). Results: Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg. Conclusions In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.

Purpose: Zinc finger protein 639 (ZNF639) is often found within the overlapping amplicon of PIK3CA, and previous studies suggest its involvement in the pathogenesis of esophageal and oral squamous cell carcinomas. However, its expression and significance in breast cancer remain uncharacterized. Methods: Immunohistochemical analysis of ZNF639 was performed using tissue microarrays.Functional studies, including colony formation, Transwell cell migration, and in vivo metastasis, were conducted on breast tumor cells with ZNF639 knockdown via small interfering RNA transfection. Results: Reduced ZNF639 immunoreactivity was observed in 82% of the breast cancer samples, independent of hormone receptor and human epidermal growth factor receptor 2 status. In multivariate Cox regression analyses, ZNF639 expression was associated with favorable survival outcomes, including recurrence-free survival (hazard ratio, 0.35; 95% confidence interval [CI], 0.14–0.89) and overall survival (hazard ratio, 0.41; 95% CI, 0.16– 1.05). ZNF639 knockdown increased clonogenicity, cell motility, and lung metastasis in NOD/ SCID mice. Following the ZNF639 knockdown, the expression of Snail1, vimentin, and C-C chemokine ligand 20 (CCL20) was upregulated, and the changes in cell phenotype mediated by ZNF639 were reversed by the subsequent knockdown of CCL20. Conclusion Low ZNF639 expression is a novel prognostic factor for recurrence-free survival in patients with breast cancer.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Purpose: Biomarkers predicting clinically significant prostate cancer (sPC) before biopsy are currently lacking. This study aimed to develop a non-invasive urine test to predict sPC in at-risk men using urinary metabolomic profiles. Materials and Methods: Urine samples from 934 at-risk subjects and 268 treatment-naïve PC patients were subjected to liquid chromatography/mass spectrophotometry (LC-MS)-based metabolomics profiling using both C18 and hydrophilic interaction liquid chromatography (HILIC) column analyses. Four models were constructed (training cohort [n=647]) and validated (validation cohort [n=344]) for different purposes. Model I differentiates PC from benign cases. Models II, III, and a Gleason score model (model GS) predict sPC that is defined as National Comprehensive Cancer Network (NCCN)-categorized favorable-intermediate risk group or higher (Model II), unfavorable-intermediate risk group or higher (Model III), and GS ≥7 PC (model GS), respectively. The metabolomic panels and predicting models were constructed using logistic regression and Akaike information criterion. Results: The best metabolomic panels from the HILIC column include 25, 27, 28 and 26 metabolites in Models I, II, III, and GS, respectively, with area under the curve (AUC) values ranging between 0.82 and 0.91 in the training cohort and between 0.77 and 0.86 in the validation cohort. The combination of the metabolomic panels and five baseline clinical factors that include serum prostate-specific antigen, age, family history of PC, previously negative biopsy, and abnormal digital rectal examination results significantly increased AUCs (range 0.88–0.91). At 90% sensitivity (validation cohort), 33%, 34%, 41%, and 36% of unnecessary biopsies were avoided in Models I, II, III, and GS, respectively. The above results were successfully validated using LC-MS with the C18 column. Conclusions Urinary metabolomic profiles with baseline clinical factors may accurately predict sPC in men with elevated risk before biopsy.