Aveir VR real-world performance and chronic pacing threshold prediction using mapping and fixation electrical data.

AIMS: Aveir VR performance and predictors for its pacing threshold (PCT) in a real-world cohort were investigated. METHODS: Electrical measurements at various stages of an Aveir VR implant were prospectively collected. Predictors for 3-month PCT were studied. A retrospective cohort of consecutive 139 Micra implants was used to compare the PCT evolution. High PCT was defined as ≥1.5 V, using a pulse width of 0.4 ms for Aveir and 0.24 ms for Micra. Excellent PCT was defined as ≤0.5 V at the respective pulse width. RESULTS: Among the 123 consecutive Aveir VR implant attempts, 122 (99.2%) were successful. The majority were of advanced age (mean 79.7) and small body size (mean BSA 1.60). Two patients (1.6%) experienced complications, including one pericardial effusion after device reposition and one intraoperative device dislodgement. Eighty-eight patients reached a 3-month follow-up. Aveir 3-month PCT was correlated with impedance at mapping (P = 0.015), tether mode (P < 0.001), end-of-procedure (P < 0.001), and mapping PCT (P = 0.035), but not with PCTs after fixation (P > 0.05). Tether mode impedance >470 ohms had 88% sensitivity and 71% specificity in predicting excellent 3-month PCT. Although it is more common for Aveir to have high PCT at end of procedure (11.5% for Aveir and 2.2% for Micra, P = 0.004), the rate at 3 months was similar (2.3% for Aveir and 3.1% for Micra, P = 1.000). CONCLUSION: Aveir VR demonstrated satisfactory performance in this high-risk cohort. Pacing thresholds tend to improve to a greater extent than Micra after implantation. The PCT after fixation, even after a waiting period, has limited predictive value for the chronic threshold. Low-mapping PCT and high intraoperative impedance predict chronic low PCT.

Addressing the risk and management of cardiometabolic complications in prostate cancer patients on androgen deprivation therapy and androgen receptor axis-targeted therapy: consensus statements from the Hong Kong Urological Association and the Hong Kong Society of Uro-Oncology.

Background: Androgen deprivation therapy (ADT) is the foundational treatment for metastatic prostate cancer (PCa). Androgen receptor (AR) axis-targeted therapies are a new standard of care for advanced PCa. Although these agents have significantly improved patient survival, the suppression of testosterone is associated with an increased risk of cardiometabolic syndrome. This highlights the urgency of multidisciplinary efforts to address the cardiometabolic risk of anticancer treatment in men with PCa. Methods: Two professional organizations invited five urologists, five clinical oncologists, and two cardiologists to form a consensus panel. They reviewed the relevant literature obtained by searching PubMed for the publication period from April 2013 to April 2023, to address three discussion areas: (i) baseline assessment and screening for risk factors in PCa patients before the initiation of ADT and AR axis-targeted therapies; (ii) follow-up and management of cardiometabolic complications; and (iii) selection of ADT agents among high-risk patients. The panel convened four meetings to discuss and draft consensus statements using a modified Delphi method. Each drafted statement was anonymously voted on by every panelist. Results: The panel reached a consensus on 18 statements based on recent evidence and expert insights. Conclusion: These consensus statements serve as a practical recommendation for clinicians in Hong Kong, and possibly the Asia-Pacific region, in the management of cardiometabolic toxicities of ADT or AR axis-targeted therapies in men with PCa.

Mid-term Results of a Novel Dedicated Venous Stent for the Treatment of Chronic Thoracic Central Vein Obstruction of Benign Aetiology.

OBJECTIVES: Endovascular treatment is indicated for the treatment of symptomatic thoracic central vein obstruction (TCVO) but is limited by high rates of restenosis and the need for re-intervention. The aim was to assess the safety and mid-term patency of a novel dedicated venous stent for the treatment of TCVO of benign aetiology. METHODS: This was a prospective single centre observational study of 20 patients (median age 65 years, 50% male) referred for the treatment of symptomatic chronic (>three months duration) TCVO between May 2016 and January 2018. Balloon angioplasty with implantation of a self expanding nitinol stent (Vici, Boston Scientific, Marlborough, MA, USA) was performed in all patients. Clinical records including demographics, aetiologies and types of TCVO, and procedural details were recorded. Patients were followed up clinically at one, six, and 12 months. Primary and assisted primary patency were reported. RESULTS: All 20 lesions were total occlusions, of which 55% (n = 11) were de novo, 10% (n = 2) peri-stent restenosis, and 35% (n = 7) in-stent re-occlusion. The aetiology of TCVO was predominantly (95%) because of multiple or prolonged central venous line insertion. The procedural success rate was 90% (18/20) with no procedural complications. The median follow up was 13.5 months. Primary patency was 100% at 6 months. One patient required re-intervention for stent in segment restenosis at 7 months. The assisted primary patency rate was 100% at 12 months. CONCLUSION: Endovascular treatment of benign TCVO with the novel dedicated venous stent was safe and effective in relieving obstructive symptoms with excellent one year patency rates.

Comprehensive identification of peptides in tandem mass spectra using an efficient open search engine.

We present a sequence-tag-based search engine, Open-pFind, to identify peptides in an ultra-large search space that includes coeluting peptides, unexpected modifications and digestions. Our method detects peptides with higher precision and speed than seven other search engines. Open-pFind identified 70-85% of the tandem mass spectra in four large-scale datasets and 14,064 proteins, each supported by at least two protein-unique peptides, in a human proteome dataset.

What's Old is New Again - A Review of the Current Evidence of Colchicine in Cardiovascular Medicine.

Colchicine is a well-established drug approved by the Food and Drug Administration (FDA) for the prevention and treatment of gout. It possesses unique anti-inflammatory properties. Interests in the usage of colchicine in cardiovascular medicine have been rekindled recently with several large trials been carried out to investigate its efficacy in treatment of various cardiac conditions including pericarditis, postpericardiotomy syndrome, atrial fibrillation and coronary artery disease. In this review, the basic pharmacological properties of colchicine will be discussed, and the evidences of its benefits for different applications in cardiovascular medicine will be reviewed.

Novel platelet ADP P2Y12 inhibitors in the treatment of acute coronary syndrome.

Inhibition of the platelet P2Y12 receptor plays an important role in the prevention of thrombotic complications of acute coronary syndrome and percutaneous coronary interventions. Despite clinical benefits with clopidogrel therapy in these high risk patients, efficacy of clopidogrel is limited by slow onset of action, variability in platelet inhibitory response and potential drug-drug interactions. Importantly, suboptimal platelet inhibition by clopidogrel is associated with worse prognosis. This underscores the need for alternate antiplatelet treatment strategies. A number of novel P2Y12 antagonists are approved or in advanced development and some have demonstrated superior platelet inhibition effect, clinical outcomes, and safety profile than clopidogrel in patients with acute coronary syndrome. The aim of this manuscript is to provide an overview on the current status in P2Y12 receptor inhibition and to review the pharmacology and clinical development of four of these agents: prasugrel, cangrelor, ticagrelor, and elinogrel.

Role of warfarin pharmacogenetic testing in clinical practice.

Chronic oral anticoagulation with warfarin is difficult to maintain within the therapeutic range and requires frequent monitoring and dose adjustments. Variations in two genes, VKORC1 and CYP2C9, have been associated with variation in warfarin metabolism among individuals. Patients with CYP2C9*2 and *3 variants have longer times to dose stabilization and are at higher risk of serious and life-threatening bleeding. VKORC1 polymorphisms significantly influence time to first therapeutic warfarin range, and variants in this gene determine low-, intermediate- and high-warfarin dose requirements. The prevalence of CYP2C9 and VKORC1 polymorphisms vary among different ethnic groups, and can account for over 30% of variance in warfarin dose. Recent studies suggest that the pharmacogenomics-guided dosing algorithm can accurately predict warfarin dosage and might reduce adverse events. We aim to review the pharmacogenetics of warfarin metabolism and the clinical role of genetic testing for warfarin therapy.

[Expression of Beclin1 in primary hepatocellular carcinoma].

OBJECTIVE: To detect Beclin1 expression and explore its clinical significance in primary hepatocellular carcinoma (HCC). METHODS: Beclin1 expressions in 10 normal hepatic tissues, 30 hepatitis liver, 30 cirrhotic liver and 50 HCC tissues were detected by immunohistochemical staining. RESULTS: The positivity rates of Beclin1 expression in the HCC, cirrhotic liver, hepatitis liver and normal liver tissues were 78.00% (39/50), 26.67% (8/30), 53.33% (16/30), and 10.00% (1/10), respectively, showing significant differences between them (chi(2)=28.31, P<0.05). Beclin1 expression was significantly higher in HCC tissues than in the cirrhotic, hepatitis and normal liver tissues (chi(2)=20.39, 5.31, and 14.41, respectively, P<0.05), and hepatitis tissues showed significantly higher Beclin1 expression than hepatic cirrhosis tissues and normal hepatic tissues (chi(2)=4.44 and 4.12, respectively, P<0.05). CONCLUSION: The abnormal expression of Beclin1 is closely associated with the pathogenesis and development of primary hepatocellular carcinoma, and may play an important role in this process.

Surveillance programme for hepatocellular carcinoma improves the survival of patients with chronic viral hepatitis.

BACKGROUND: The survival benefit of surveillance for hepatocellular carcinoma (HCC) is controversial. AIM: We aimed to examine the survival benefit of HCC surveillance in chronic viral hepatitis. METHODS: Survivals of HCC patients related to chronic viral hepatitis from the Hepatology Clinic (surveillance group) were compared with those referred from other hospitals/clinics (no-surveillance group). Lead-time and length-time biases were adjusted based on tumour volume doubling times. RESULTS: Among 579 patients (91% hepatitis B), 472 (82%) patients had HCC and 79 (17%) of these patients were referred from the surveillance programme. HCC was smaller (4.2 vs. 7.7 cm; P<0.001) and fewer in numbers (2.6 vs. 3.8, P=0.03) in the surveillance group vs. the no-surveillance group. Treatment by surgery (20 vs. 10%, P=0.007) and local ablative therapy (46 vs. 19%, P<0.001) were more frequent in the surveillance group than that in the no-surveillance group. The median survival of the surveillance group (88 weeks) was significantly longer than that of the no-surveillance group (26 weeks) (P<0.001). The adjusted cumulative survival at 2 years was significantly longer in the surveillance group if the tumour volume doubling time was <90 days (P=0.0352). CONCLUSIONS: HCC surveillance can improve the survival of patients with chronic viral hepatitis B.

[Clinicopathologic features of dendritic fibromyxolipoma].

OBJECTIVE: To study the clinicopathologic features of dendritic fibromyxolipoma for the purpose of differentiating it from other confusable soft tissue neoplasms. METHODS: Eight cases of dendritic fibromyxolipoma were obtained and their clinicopathologic features were studied. Immunohistochemistry stains for CD34, bcl-2, vimentin, cytokeratin, EMA, S-100, HHF35 and smooth muscle actin were performed with labeled streptavidin-biotin (SLAB) system on DAKO auto-immunohistochemical stainer. RESULTS: Dendritic fibromyxolipoma usually occurrs in middle-aged to elderly men, developing primarily in the subcutis or muscular fascia of the head and neck region, shoulder, back, calf and foot. Grossly, it is well-circumscribed, partly thinly encapsulated lesion with focal mucinous or gelatinous cutting surface. Histologically, all these tumors showed similar histological features., and were characterized by an admixture of mature adipose tissue, spindle and stellate cells, and abundant myxoid stroma with prominent collagenization. The proportion of above elements varied in different tumors or in different areas within the same tumor. One of the pathologic characteristics was the proliferation of spindle cells and stellate cells showing thin cytoplasmic dendritic prolongations. No cytological atypia or mitotic activity could be identified. Furthermore, the lesions were well-vascularized and the vascular elements consisted of small to median-sized and capillary-sized plexiform vessels. Spindle cells were strongly positive for CD34, bcl-2 and vimentin but negative for S-100 protein and epithelial and muscle markers. CONCLUSIONS: Dendritic fibromyxolipoma is characterized by clinicopathologic and immunohistochemical features. Based on those features of this tumor, this entity appears to represent a transitional form between spindle cell lipoma and solitary fibrous tumor, and should be distinguished from myxiod liposarcoma and myxoid malignant fibrous histiocytoma. Due to the benign nature of this lesion, simple local excision is curative.