Potential Overtreatment of DCIS in Patients with Limited Life Expectancy.

INTRODUCTION: As the benefits of intensive locoregional therapy for ductal carcinoma in situ (DCIS) are realized over time in older adults, life expectancy may help to guide treatment decisions. We examined whether life expectancy was associated with extent of locoregional therapy in this population. PATIENTS AND METHODS: Women ≥ 70 years old with < 5 cm of DCIS diagnosed 2010-2015 were identified in the Surveillance, Epidemiology, and End Results (SEER)-Medicare dataset and categorized by a life expectancy ≤ 5 or > 5 years, defined by a validated claims-based measure. Differences in locoregional therapy (mastectomy + axillary surgery, mastectomy-only, lumpectomy + radiation therapy (RT) + axillary surgery, lumpectomy + RT, lumpectomy-only, and no treatment) by life expectancy were assessed using Pearson chi-squared tests. Generalized linear mixed models were used to identify factors associated with receipt of lumpectomy-only. RESULTS: Of 5346 women (median age of 75 years, range 70-97 years), 927 (17.3%) had a life expectancy ≤ 5 years. Of the 4041 patients who underwent lumpectomy, 710 (13.3%) underwent axillary surgery. More patients with life expectancy ≤ 5 years underwent lumpectomy-only (39.4% versus 27%), mastectomy-only (8.1% versus 5.3%), or no treatment (5.8% versus 3.2%; p < 0.001). On multivariable analysis, women with life expectancy ≤ 5 years had a significantly greater likelihood of undergoing lumpectomy-only [OR 1.90, 95% CI (1.63-2.22)]. CONCLUSIONS: Life expectancy is associated with lower-intensity locoregional therapy for older women with DCIS, yet a large proportion of patients with a life expectancy ≤ 5 years received RT and axillary surgery, highlighting potential overtreatment and opportunities to de-escalate locoregional therapy in older adults.

A Self-Cascade Penetrating Brain Tumor Immunotherapy Mediated by Near-Infrared II Cell Membrane-Disrupting Nanoflakes via Detained Dendritic Cells.

Immunotherapy can potentially suppress the highly aggressive glioblastoma (GBM) by promoting T lymphocyte infiltration. Nevertheless, the immune privilege phenomenon, coupled with the generally low immunogenicity of vaccines, frequently hampers the presence of lymphocytes within brain tumors, particularly in brain tumors. In this study, the membrane-disrupted polymer-wrapped CuS nanoflakes that can penetrate delivery to deep brain tumors via releasing the cell-cell interactions, facilitating the near-infrared II (NIR II) photothermal therapy, and detaining dendritic cells for a self-cascading immunotherapy are developed. By convection-enhanced delivery, membrane-disrupted amphiphilic polymer micelles (poly(methoxypoly(ethylene glycol)-benzoic imine-octadecane, mPEG-b-C18) with CuS nanoflakes enhances tumor permeability and resides in deep brain tumors. Under low-power NIR II irradiation (0.8 W/cm2), the intense heat generated by well-distributed CuS nanoflakes actuates the thermolytic efficacy, facilitating cell apoptosis and the subsequent antigen release. Then, the positively charged polymer after hydrolysis of the benzoic-imine bond serves as an antigen depot, detaining autologous tumor-associated antigens and presenting them to dendritic cells, ensuring sustained immune stimulation. This self-cascading penetrative immunotherapy amplifies the immune response to postoperative brain tumors but also enhances survival outcomes through effective brain immunotherapy.

Prostate magnetic resonance imaging utilization and its relationship with advanced prostate cancer detection.

BACKGROUND: The rise in advanced prostate cancer has coincided with increased use of Magnetic Resonance Imaging (MRI), leading to the hypothesis that this increase in surveillance registries is an artifact of more sensitive imaging tools. We assessed the association between regional variation in prostate MRI and advanced prostate cancer diagnoses. METHODS: We utilized SEER-Medicare data (2004-2015), including men > 65 diagnosed with localized prostate cancer. The predictor variable was the utilization of prostate MRI in each hospital referral region (HRR, representing regional healthcare markets). We compared the proportion of disease recorded as locally advanced or of regional risk group (cT3, cT4, and cN1) which would plausibly have been detected by prostate MRI. We conducted adjusted multivariable analysis and performed correlation analysis with Spearman rank coefficient at the level of the HRR. Sensitivity analysis for years 2011 to 2015 was conducted. RESULTS: Of 98,921 men diagnosed, 4.01% had locally advanced or regional disease. The median prostate MRI utilization rate was 4.58% (IQR [3.03%, 8.12%]). Adjusted multivariable analysis revealed no statistically significant correlation between MRI utilization and proportion of advanced prostate cancer (aOR = 1.01, 95% CI, [0.99,1.03]) in each region. The correlation between MRI usage and advanced diagnosis was not significant (Spearman Ρ = 0.09, P = 0.4). Sensitivity analysis conducted between 2011 and 2015 showed similar results (aOR = 1.008, 95% CI, [0.989, 1.027]; Spearman Ρ = 0.16, P = 0.1). CONCLUSIONS: During our study period, HRR-level utilization of MRI was not associated with higher incidences of advanced prostate cancer. This suggests the rising advanced prostate cancer diagnoses observed in this period are unlikely an artifact of greater sensitivity of modern imaging tests, but potentially due to other factors such as changes in screening or risk factors. With increased utilization and evolving techniques in recent years, the association between MRI and advanced prostate cancer detection warrants continued monitoring.

Cordycepin Augments the Efficacy of Anti-PD1 against Colon Cancer.

Colon cancer has a poor clinical response to anti-PD1 therapy. This study aimed to evaluate the effect of cordycepin on the efficacy of anti-PD1 treatment in colon cancer. The viability of CT26 mouse colon carcinoma cells, cell-cycle progression, morphology, and the expression of mRNA and protein were assessed. A syngeneic animal model was established by implanting CT26 cells into BALB/c mice for in vivo experiments. Multi-parameter flow cytometry was used to analyze the splenic cell lineages and tumor microenvironment (TME). The in vitro data revealed that cordycepin, but not adenosine, inhibited CT26 cell viability. The protein, but not mRNA, expression levels of A2AR and A2BR were suppressed by cordycepin but not by adenosine in CT26 cells. The combination of cordycepin, but not adenosine, with anti-PD1 exhibited a greater tumor-inhibitory effect than anti-PD1 alone as well as inhibited the expression of A2AR and A2BR in splenic macrophages. In the TME, the combination of cordycepin and anti-PD1 increased the number of CD3+ T cells and neutrophils and decreased the number of natural killer (NK) cells. Overall, cordycepin augmented the antitumor effects of anti-PD1 against mouse colon carcinoma cells and inhibited the expression of the adenosine receptors A2AR and A2BR in splenic macrophages and intratumoral NK cells.

Effectiveness of fentanyl buccal soluble film in cancer patients with inadequate breakthrough pain control.

BACKGROUND: Clinical evidence for the rapidity and effectiveness of fentanyl buccal soluble film (FBSF) in reducing pain intensity of breakthrough cancer pain (BTcP) remains inadequate. This study aimed to evaluate the efficacy of FBSF proportional to the around-the-clock (ATC) opioid regimens in rapidly relieving the intensity of BTcP episodes by determining the percentage of patients requiring further dose titration. METHODS: The study procedure included a dose-finding period followed by a 14-day observation period. Pain intensity was recorded with a Numeric Rating Scale (NRS) at onset and 5, 10, 15, and 30 min after FBSF self-administration. Meaningful pain relief was defined as the final NRS score ≤ 3. Satisfaction survey was conducted for each patient after treatment using the Global Satisfaction Scale. RESULTS: A total of 63 BTcP episodes occurred in 30 cancer patients. Only one patient required rescue medication at first BTcP episode and then achieved meaningful pain relief after titrating FBSF by 200 µg. Most BTcP episodes relieved within 10 min. Of 63 BTcP episodes, 30 (47.6%), 46 (73.0%), and 53 (84.1%) relieved within 5, 10, and 15 min after FBSF administration. Only grade 1/2 adverse events were reported, including somnolence, malaise, and dizziness. Of the 63 BTcP episodes, 82.6% were rated as excellent/good satisfaction with FBSF. CONCLUSION: FBSF can be administrated "on demand" by cancer patients at the onset of BTcP, providing rapid analgesia by achieving meaningful pain relief within 10 min. TRIAL REGISTRATION: This study was retrospectively registered 24 December, 2021 at Clinicaltrial.gov (NCT05209906): https://clinicaltrials.gov/study/NCT05209906 .

A Randomized Crossover Trial Evaluating the Impact of Cultural Dexterity Training on Surgical Residents' Knowledge, Cross-Cultural Care, Skills, and Beliefs: The Provider Awareness and Cultural dexterity Training for Surgeons (PACTS) Trial.

OBJECTIVES: This trial examines the impact of the Provider Awareness and Cultural dexterity Toolkit for Surgeons (PACTS) curriculum on surgical residents' knowledge, cross-cultural care, skills, and beliefs. SUMMARY BACKGROUND DATA: Cross-cultural training of providers may reduce healthcare outcome disparities, but its effectiveness in surgical trainees is unknown. METHODS: PACTS focuses on developing skills needed for building trust, working with patients with limited English proficiency, optimizing informed consent, and managing pain. The PACTS trial was a randomized crossover trial of 8 academic general surgery programs in the United States: The Early group ("Early") received PACTS between Periods 1 and 2, while the Delayed group ("Delayed") received PACTS between Periods 2 and 3. Residents were assessed pre- and post-intervention on Knowledge, Cross-Cultural Care, Self-Assessed Skills, and Beliefs. Chi-square and Fisher's exact tests were conducted to evaluate within- and between-intervention group differences. RESULTS: Of 406 residents enrolled, 315 were exposed to the complete PACTS curriculum. Early residents' Cross-Cultural Care (79.6% to 88.2%, P<0.0001), Self-Assessed Skills (74.5% to 85.0%, P<0.0001), and Beliefs (89.6% to 92.4%, P=0.0028) improved after PACTS; Knowledge scores (71.3% to 74.3%, P=0.0661) were unchanged. Delayed resident scores pre- to post-PACTS showed minimal improvements in all domains. When comparing the two groups at Period 2, Early residents had modest improvement in all 4 assessment areas, with statistically significant increase in Beliefs (92.4% vs 89.9%, P=0.0199). CONCLUSION: The PACTS curriculum is a comprehensive tool that improved surgical residents' knowledge, preparedness, skills, and beliefs, which will help with caring for diverse patient populations.

A 35-gene mutation profile predicts the therapeutic outcome of patients with esophageal squamous cell carcinoma receiving neo-adjuvant chemoradiation.

Esophageal cancer is a common malignancy worldwide with a poor prognosis without radical resection. Neoadjuvant concurrent chemoradiotherapy (NACRT) followed by esophagectomy is widely used for treating locally advanced esophageal cancer in the thorax. The study aimed to assess mutation profiles and their correlation with therapeutic outcomes in patients diagnosed with locally advanced thoracic esophageal squamous cell carcinoma (ESCC). A retrospective analysis was conducted on 62 patients with ESCC who underwent NACRT. All patients received concurrent chemoradiotherapy (CCRT) utilizing intensity-modulated radiation therapy alongside concurrent chemotherapy with a cisplatin-based regimen. A 35-gene next-generation sequencing (NGS) panel detecting 402 genetic variants was used, which has been proven predictive in ESCC patients who received definitive chemoradiation. The 35-gene mutation profiles were analyzed in pre-treatment biopsies. The results reveled there were variants correlated with pathological complete remission or partial response, overall survival, and progression-free survival. A combination of p.Pro1319Ser and p.Arg2159Gly mutations in the MUC17 gene demonstrated an adverse impact on pathological response (OR [95% CI] = 7.00 (3.07-15.94), P < 0.001). Additionally, the variants located in the MUC17, MUC4, and MYH4 genes exhibited notably effects on tumor recurrence or mortality. Patients harboring either the MUC17 p.Thr2702Val or MUC4 p.Thr3355Ser mutation displayed a more than four-fold increased risk for disease recurrence or mortality. We concluded that specific mutations correlated to the pathological complete response in ESCC receiving neoadjuvant chemoradiation can be identified through the utilization of 35-gene expression profiles. Further investigation into the pathophysiological roles of MUC17 and MUC4 mutations in ESCC is warranted.

FK228 suppress the growth of human malignant pleural mesothelioma tumor independent to epithelioid or non-epithelioid histology.

Human malignant pleural mesothelioma (hMPM) is an aggressive, rare disease with a poor prognosis. Histologically, MPM is categorized into epithelioid, biphasic, and sarcomatoid subtypes, with the epithelioid subtype generally displaying a better response to treatment. Conversely, effective therapies for the non-epithelioid subtypes are limited. This study aimed to investigate the potential role of FK228, a histone deacetylase inhibitor, in the suppression of hMPM tumor growth. We conducted a comprehensive analysis of the histological and molecular characteristics of two MPM cell lines, CRL-5820 (epithelioid) and CRL-5946 (non-epithelioid). CRL-5946 cells and non-epithelioid patient-derived xenografted mice exhibited heightened growth rates compared to those with epithelioid MPM. Both CRL-5946 cells and non-epithelioid mice displayed a poor response to cisplatin. However, FK228 markedly inhibited the growth of both epithelioid and non-epithelioid tumor cells in vitro and in vivo. Cell cycle analysis revealed FK228-induced G1/S and mitotic arrest in MPM cells. Caspase inhibitor experiments demonstrated that FK228-triggered apoptosis occurred via a caspase-dependent pathway in CRL-5946 but not in CRL-5820 cells. Additionally, a cytokine array analysis showed that FK228 reduced the release of growth factors, including platelet-derived and vascular endothelial growth factors, specifically in CRL-5946 cells. These results indicate that FK228 exhibits therapeutic potential in MPM by inducing cytotoxicity and modulating the tumor microenvironment, potentially benefiting both epithelioid and non-epithelioid subtypes.

Comparison of modified Furlow palatoplasty using small double-opposing Z-plasty and conventional Furlow palatoplasty: A long-term outcome study.

BACKGROUND: The aim of palatoplasty is to create a functional palate to achieve normal speech, while minimizing post-operative complications. This study aimed to compare the long-term outcomes of modified Furlow palatoplasty using small double-opposing Z-plasty (small-DOZ) and conventional Furlow palatoplasty (conventional-DOZ) performed in a single center. METHODS: A retrospective review of consecutive patients who underwent Furlow palatoplasty between May 2007 and March 2014 was executed. Non-syndromic patients subjected to palatoplasty prior to 24 months of age and followed-up until at least 9 years of age were included. RESULTS: A total of 196 small-DOZ and 280 conventional-DOZ palatoplasty patients were included in this study. Overall, 14 patients (2.9%) developed oronasal fistula, and 40 patients (8.4%) received velopharyngeal insufficiency (VPI) surgery. In comparisons, oronasal fistula rate was significantly higher in conventional-DOZ (0.5% vs. 4.6%, p = 0.01), and the VPI prevalence was not significantly different (9.2% vs. 7.9%, p = 0.62). Patients who developed fistula had a significantly higher likelihood of developing VPI than patients without oronasal fistula (50.0% vs. 7.1%, respectively; p < 0.01), with an odds ratio of 13.0. CONCLUSION: Both modalities of palatoplasty yielded commendable velopharyngeal function in the long-term follow-up. The small-DOZ with reduced tension lowered the risk of oronasal fistula.

Achieve fairness without demographics for dermatological disease diagnosis.

In medical image diagnosis, fairness has become increasingly crucial. Without bias mitigation, deploying unfair AI would harm the interests of the underprivileged population and potentially tear society apart. Recent research addresses prediction biases in deep learning models concerning demographic groups (e.g., gender, age, and race) by utilizing demographic (sensitive attribute) information during training. However, many sensitive attributes naturally exist in dermatological disease images. If the trained model only targets fairness for a specific attribute, it remains unfair for other attributes. Moreover, training a model that can accommodate multiple sensitive attributes is impractical due to privacy concerns. To overcome this, we propose a method enabling fair predictions for sensitive attributes during the testing phase without using such information during training. Inspired by prior work highlighting the impact of feature entanglement on fairness, we enhance the model features by capturing the features related to the sensitive and target attributes and regularizing the feature entanglement between corresponding classes. This ensures that the model can only classify based on the features related to the target attribute without relying on features associated with sensitive attributes, thereby improving fairness and accuracy. Additionally, we use disease masks from the Segment Anything Model (SAM) to enhance the quality of the learned feature. Experimental results demonstrate that the proposed method can improve fairness in classification compared to state-of-the-art methods in two dermatological disease datasets.

New-Onset Atrial Fibrillation Is a Red Flag to Microvascular Free Tissue Transfer Failure in Head and Neck Cancer Patients.

BACKGROUND: Postoperative new-onset atrial fibrillation (AF) has been shown to be associated with increased surgical morbidity and mortality following cancer ablation surgery. However, evidence of new-onset AF's impact on surgical outcomes in head and neck cancer patients undergoing tumor ablation and microvascular free tissue transfer remains scarce. This study aims to evaluate the association between AF and surgical outcomes in these patients. METHODS: We enrolled head and neck cancer patients who underwent tumor ablation reconstructed with microvascular free tissue transfer from the National Health Insurance Research Database (NHIRD). Patients were grouped into the following: (1) without AF, (2) new-onset AF, and (3) preexisting AF. The groups were matched by propensity score based on age, gender, cancer stage, and comorbidities. The primary outcome was postoperative complications, whereas all-cause mortality was the secondary outcome. RESULTS: In total, 26,817 patients were included in this study. After matching, we identified 2,176 (79.24%) patients without AF, 285 (10.37%) with preexisting AF, and 285 (10.37%) with new-onset AF. Our results demonstrated that the free flap failure rate was twofold escalated in patients with new-onset AF (9.8%) compared to those without AF (5.4%) or preexisting AF (5.3%; p = 0.01). However, we did not identify significant differences among other postoperative complications across groups. Additionally, we found that the risk of all-cause mortality was significantly elevated in patients with preexisting AF (p < 0.001) compared to those without AF or new-onset AF. CONCLUSION: Our study demonstrated that new-onset AF is associated with an increased risk of flap failure and could serve as a predictor. On the other hand, all-cause mortality in patients with preexisting AF was significantly elevated. Close postoperative monitoring in patients with new-onset and preexisting AF is crucial to identify any potential adverse effects.

Cimetidine Attenuates Therapeutic Effect of Anti-PD-1 and Anti-PD-L1 and Modulates Tumor Microenvironment in Colon Cancer.

Histamine modulates immunity by binding to histamine receptor 2 (H2R). Cimetidine, an H2R antagonist that inhibits gastric acid secretion and treats gastrointestinal ulcers, interferes with histamine-mediated immunomodulation and may have anticancer activity. This study examined cimetidine's effect on the anticancer effect of anti-PD-L1 in colon cancer. The MTT assay, colony formation assay, and DNA histograms assessed cell viability, clonogenicity, and cell cycle distribution, respectively. Flow cytometry measured H2R and PD-L1 expression and estimated specific immune cell lineages. For the in vivo study, tumor cells were subcutaneously implanted into the right flank of BALB/c mice. Cimetidine had no significant effect on CT26 cell viability, clonogenicity, or cell cycle distribution. It also did not affect H2R and PD-L1 expression levels in CT26 cells. In vivo, anti-PD-1 and anti-PD-L1 suppressed CT26 tumor growth, whereas cimetidine showed mild antitumor activity. In the combined experiment, cimetidine significantly attenuated anti-PD-1 and anti-PD-L1' antitumor effects without major toxicity. In the tumor microenvironment, anti-PD-L1 increased CD3+ T, CD4+ T, and CD8+ T cells and M1 macrophages. Combined treatment with cimetidine reversed this. Cimetidine also reversed anti-PD-1 and anti-PD-L1's decrease in circulating and tumor-associated neutrophils. Cimetidine attenuated anti-PD-L1's antitumor effect and modulated the tumor microenvironment in colon cancer.

Mac-2-Binding Protein Glycosylation Isomer to Albumin Ratio Predicts Bacterial Infections in Cirrhotic Patients.

INTRODUCTION: Mac-2-binding protein glycosylation isomer (M2BPGi) is a novel biomarker for liver fibrosis, but little is known about its role in cirrhosis-associated clinical outcomes. This study aimed to investigate the predictive role of M2BPGi in cirrhosis-associated complications. METHODS: One hundred and forty-nine cirrhotic patients were retrospectively enrolled. Patients were followed up for 1 year, and cirrhosis-associated clinical events were recorded. Receiver operating characteristic curve (ROC) analysis was used to establish the values of the predictive models for cirrhotic outcomes, and Cox proportional hazards regression models were used to identify predictors of clinical outcomes. RESULTS: Sixty (40.3%) patients experienced cirrhosis-associated clinical events and had higher M2BPGi levels compared to those without events (8.7 vs. 5.1 cutoff index, p < 0.001). The most common cirrhosis-associated complications were bacterial infections (24.2%). On ROC analysis, M2BPGi to albumin ratio (M2BPGi/albumin) had comparable discriminant abilities for all cirrhosis-associated events (area under the ROC curve [AUC] = 0.74) compared with M2BPGi, Child-Pugh, model for end-stage liver disease, albumin-bilirubin scores, and neutrophil-to-lymphocyte ratio and was superior to M2BPGi alone for all bacterial infectious events (AUC = 0.80). Cox regression analysis revealed that the M2BPGi/albumin, but not M2BPGi alone, independently predicted all cirrhosis-associated events (hazard ratio [HR] = 1.34, p = 0.038) and all bacterial infectious events (HR = 1.51, p = 0.011) within 1 year. However, M2BPGi/albumin did not predict other cirrhotic complications and transplant-free survival. DISCUSSION/CONCLUSION: M2BPGi/albumin might serve as a potential prognostic indicator for patients with cirrhosis, particularly for predicting bacterial infections.

Influence of Verbal Instruction on Gait Training in Parkinson Disease: A Randomized Controlled Trial.

OBJECTIVE: Verbal instruction is one of the most commonly used methods that therapists use to correct walking pattern for people with Parkinson disease. This study aimed to compare the long-term training effects of two different verbal instructions that either asked the participants to "take big steps" or "strike the ground with the heel" on walking ability in individuals with Parkinson disease. DESIGN: Forty-five participants with Parkinson disease were randomized into the big-step or heel strike group. The participants underwent 12 sessions of treadmill and overground gait training. Throughout the interventions, the big-step group received an instruction to "take big steps," while the heel strike group received an instruction to "strike the ground with your heel." The primary outcome was gait performance, including velocity, stride length, cadence, and heel strike angle. The participants were assessed before, immediately after, and 1 mo after training. RESULTS: Both groups showed significant improvements in gait performance after training. The heel strike group showed continuous improvements in velocity and stride length during the follow-up period; however, the big-step group showed slightly decreased performance. CONCLUSIONS: A verbal instruction emphasizing heel strike can facilitate long-term retention of walking performance in people with Parkinson disease.

Effect of bone marrow aspiration concentrate and platelet-rich plasma combination in anterior cruciate ligament reconstruction: a randomized, prospective, double-blinded study.

BACKGROUND: The effect of bone marrow aspirate concentrate (BMAC) and platelet-rich plasma (PRP) combination in enhancing graft maturation and tendon-bone tunnel interfacial healing after anterior cruciate ligament (ACL) reconstruction remains unclear. We hypothesised that BMAC and PRP combination could lead to better clinical results and better graft maturation/interface healing than PRP alone or conventional ACL reconstruction without any other biologic augmentation. METHODS: In this randomised double-blind prospective study, patients undergoing ACL reconstruction surgery were randomly assigned into three groups: (1) control group (without any biologic augmentation), (2) PRP treatment group, and (3) combined BMAC and PRP (BMAC + PRP) group. Moreover, they were evaluated using the clinical functional score, laxity examination, and magnetic resonance imaging (MRI) analysis. RESULTS: No significant difference was observed in the improvement of functional scores among groups. However, laxity improvement at 24 weeks showed a significant difference with the BMAC + PRP group having the lowest laxity. MRI analysis showed no significant change in whole graft maturation among groups. In particular, the BMAC + PRP group showed delayed signal peak and higher graft signal at 24 weeks compared with the other two groups; however, the difference was not significant. With regard to tendon-bone interfacial healing, the BMAC + PRP group showed significantly wider tendon-bone interface in the femoral bone tunnel at 24 weeks compared with the other two groups. Moreover, the BMAC + PRP group showed significantly higher peri-tunnel edema signal in the femoral bone tunnel at 12 weeks compared with the other two groups. CONCLUSION: PRP alone and BMAC and PRP combination showed limited enhancing effect in clinical function, graft maturation and tendon-bone interfacial healing compared with control (no additional treatment). When BMAC is used in ACL reconstruction, the possibility of greater inflammation in the early stage to graft maturation and bone tunnel healing should be considered.

Endoscopic variceal ligation versus propranolol for the primary prevention of oesophageal variceal bleeding in patients with hepatocellular carcinoma: an open-label, two-centre, randomised controlled trial.

OBJECTIVE: This randomised trial aimed to address whether endoscopic variceal ligation (EVL) or propranolol (PPL) is more effective at preventing initial oesophageal variceal bleeding (EVB) in patients with hepatocellular carcinoma (HCC). DESIGN: Patients with HCC and medium-to-large oesophageal varices (EVs) but without previous EVB were randomised to receive EVL (every 3-4 weeks until variceal eradication) or PPL (up to 320 mg daily) at a 1:1 ratio. Long-term follow-up data on EVB, other upper gastrointestinal bleeding (UGIB), non-bleeding liver decompensation, overall survival (OS) and adverse events (AEs) were analysed using competing risk regression. RESULTS: Between June 2011 and April 2021, 144 patients were randomised to receive EVL (n=72) or PPL (n=72). In the EVL group, 7 patients experienced EVB, and 30 died; in the PPL group, 19 patients had EVB, and 40 died. The EVL group had a lower cumulative incidence of EVB (Gray's test, p=0.009) than its counterpart, with no mortality difference (Gray's test, p=0.085). For patients with Barcelona Clinic Liver Cancer (BCLC) stage A/B, EVL was better than PPL in reducing EVB (p<0.001) and mortality (p=0.003). For patients beyond BCLC stage B, between-group outcomes were similar. Other UGIB, non-bleeding liver decompensation and AEs did not differ between groups. A competing risk regression model confirmed the prognostic value of EVL. CONCLUSION: EVL is superior to PPL in preventing initial EVB in patients with HCC. The benefits of EVL on EVB and OS may be limited to patients with BCLC stage A/B and not to those with BCLC stage C/D. TRIAL REGISTRATION NUMBER: NCT01970748.

Cardiac and renal outcomes of direct oral anticoagulants in patients with atrial fibrillation.

BACKGROUND: Oral anticoagulation therapy with warfarin or direct oral anticoagulants (DOACs) is the mainstay for stroke prevention in patients with non-valvular atrial fibrillation (AF). The DOACs might have a lower risk of declining renal function than warfarin. This study aimed to compare renal outcomes among rivaroxaban, edoxaban, dabigatran, and warfarin. METHOD: This cohort study identified 2203 adults with AF who started anticoagulation therapy between 1 July 2013 and 31 December 2020, in a clinical database at a single centre. Inverse probability of treatment weighting was adopted to balance baseline characteristics among four anticoagulants treatment groups. The primary outcome was a composite of cardiac and renal outcomes, involving a ≥30% decline in estimated glomerular filtration rate (eGFR), renal failure and cardiovascular death. RESULTS: After propensity score weighting, dabigatran was associated with significantly lower risks of a ≥30% decline in eGFR (hazard ratio [HR]: .69, 95% confidence interval [CI]: .497-.951, p = .0237), doubling of the serum creatinine level (HR: .49, 95% CI: .259-.927, p = .0282) and the cardiac and renal outcome composite (HR: .67, 95% CI: .485-.913, p = .0115) than warfarin. Rivaroxaban and edoxaban did not show significant protective effects on renal outcomes compared to warfarin. CONCLUSION: In this study, patients treated with dabigatran had significantly reduced risks of declining renal function and composite cardiac and renal events than those treated with warfarin. However, rivaroxaban and edoxaban were not associated with lower risks of any renal outcomes than warfarin. More studies are warranted to investigate and compare the impact of renal function between different DOACs in patients with AF.