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Efficacy and Safety of Direct Oral Anticoagulants Versus Warfarin in Patients with Non-valvular Atrial Fibrillation and Liver Cirrhosis

AbstractBackgroundEvidence of the pharmacodynamics of direct oral anticoagulants (DOACs) is limited in patients with atrial fibrillation (AF) and liver cirrhosis (LC). This study aimed to compare the efficacy and safety of DOACs versus warfarin in patients with non-valvular AF and LC.MethodsWe conducted a new-user, retrospective cohort study involving patients with AF and LC from the Chang Gung Hospital System for the years 2012–2021. LC was categorized per the Child–Pugh classification system. We divided the included patients into two cohorts, namely a DOAC cohort and a warfarin cohort. The measured outcomes were thromboembolic events (ischemic stroke [IS], transient ischemic attack [TIA], and systemic embolism [SE]), intracranial hemorrhage [ICH], gastrointestinal (GI) and major bleeding, and all-cause mortality.ResultsIn total, 478 DOAC users and 247 warfarin users were included in the analysis. DOACs and warfarin exhibited comparable efficacy in preventing thromboembolic events, namely IS (adjusted hazard ratio [aHR], 1.05; 95% confidence interval [CI], 0.42–2.61), TIA (aHR, 1.36; 95% CI, 0.18–10.31]), and SE (aHR, 0.49; 95% CI, 0.14–1.70). DOAC use was associated with a similar risk of ICH (aHR, 0.65; 95% CI, 0.26–1.59) and GI bleeding (aHR, 0.64; 95% CI, 0.39–1.03), a decreased risk of major bleeding (aHR, 0.64; 95% CI, 0.42–0.99), and a reduction in all-cause mortality (aHR, 0.73; 95% CI, 0.54–0.99). Patients with Child– Pugh class A classification exhibited a significant reduction in major bleeding risk in DOAC users (aHR, 0.48; 95% CI, 0.33–0.70); however, this reduction was nonsignificant for patients with class B or C classification (aHR, 0.77; 95% CI, 0.54−1.08)ConclusionRelative to warfarin, DOACs provide comparable efficacy but greater safety for patients with non-valvular AF and LC. Specifically, DOAC use leads to a lower risk of major bleeding and a lower all-cause mortality.Clinical PerspectiveWhat is New?This study reveals that direct oral anticoagulants (DOACs) and warfarin have similar effectiveness in preventing thromboembolic events in patients with non-valvular atrial fibrillation (AF) and liver cirrhosis (LC).DOACs demonstrate a lower risk of major bleeding and reduced all-cause mortality compared to warfarin, especially in patients with Child–Pugh class A LC.The safety profile of DOACs in reducing gastrointestinal bleeding is comparable to that of warfarin, with a trend towards lower risk.What are the Clinical Implications?For patients with non-valvular AF and LC, particularly those with Child–Pugh class A classification, DOACs may be a safer alternative to warfarin due to their lower risk of major bleeding.Clinicians can consider DOACs as a comparable alternative to warfarin for stroke prevention in this patient group, given their similar efficacy in preventing thromboembolic events.The reduced all-cause mortality associated with DOACs highlights their potential benefit in improving overall patient outcomes in the context of AF and LC.

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Clonal Evolution of Der(1;7)(q10;p10) Myeloid Neoplasms

Background der(1;7)(q10;p10) (der(1;7)) is a recurrent unbalanced translocation found in 1.5~6% of MDS and AML patients. It is caused by rearrangement of centromere alpha satellites in chromosomes 1 and 7 resulting in an amplification of 1q and a deletion of 7q. Previous studies comparing der(1;7)(+) cases to those with other lesions of 7q loss (-7/del(7q)) demonstrated a higher frequency of RUNX1 mutations, no TP53 mutations and a better prognosis for der(1;7) cases suggesting that der(1;7)(+) may define a unique entity of myeloid neoplasms (MN). However, with the lack of comprehensive molecular characterization using unbiased platforms such as whole genome/exome sequencing, the entire picture of der(1;7)(+) MN still remains unclear. Methods We enrolled a total of 148 MN cases harboring der(1;7) and an additional 3,238 der(1;7)(−) MN cases: -7/del(7q), +1q and ‘OTHER’. We first analyzed paired tumor/normal DNA from 26 der(1;7) cases using whole exome sequencing (WES), followed by targeted-capture sequencing of 329 genes, including those commonly mutated in MN and others newly identified in der(1;7) cases in WES. To investigate the origin of der(1;7)(+) MN, we also enrolled 11,234 healthy individuals to evaluate der(1;7) in clonal hematopoiesis, in which der(1;7) was detected on based on SNP array-based karyotyping. Results In accordance with previous reports, der(1;7) MDS cases showed an improved overall survival (OS) compared to -7/del(7q) MDS cases (Hazard Ratio (HR) =0.71, p=0.098), which however, was shorter than OS in +1q (HR=1.36, p=0.11) and ‘OTHER’ (HR=1.8, p<0.001) MDS cases. der(1;7)(+) cases were characterized by very high mortality from infection (45.5%), while mortality from disease progression was less common (36.4%), showing a sharp contrast to -7/del(7q) and ‘OTHER’ MDS cases which had 13.9% and 10.8% infection-related deaths, and 72.3% and 76.9% disease progression, respectively (Figure 1A.). WES in 26 der(1;7)(+) cases revealed a novel transcription factor, MYB in 2 cases, which was found in 18 (12%) of 148 der(1;7) cases using targeted-capture sequencing. der(1;7)(+) cases were characterized by high frequency of mutations in transcription factors, including RUNX1 (37.8%), GATA2 (12%), ETV6 (13%), and BCOR (14%) (Figure 1B.), which were significantly more frequent in der(1;7) cases than other sub-types (Odds Ratio (OR)<6)(Figure 1B.). Very high frequency of ETNK1 mutations is highly unique to der(1;7)(+) cases (18.9%) compared to that in other cases (<10%). High frequency of mutations in transcription factors seems to be a unique feature of der(1;7)(+) cases. Trisomy 8 and del(20q) CNAs were also common in der(1;7) cases (16% and 21%, respectively). Together with DNMT3A and del(20q), der(1;7) showed the highest variant allele frequency (VAF), suggesting the early origin of these lesions. Additionally, we identified der(1;7) in 6 out of 11,234 healthy individuals using SNP array-based highly sensitive copy number detection, of which 4 died from MDS, suggesting that der(1;7)(+) clonal hematopoiesis might be the origin of MDS in these cases. Moreover, we also analyzed longitudinal samples from 9 der(1;7)(+) cases using duplex-sequencing, der(1;7) showed consistently high VAF, further supporting that der(1;7) tended to represent the major clone. Conclusion Showing a unique set of co-mutation pattern and clinical features, der(1;7) MN defines a distinct subset of myeloid neoplasms, which may originate from der(1;7)(+) clonal hematopoiesis. der(1;7)(+) patients were at higher risk of life-threatening infection, which needs to be carefully prevented and monitored during their clinical course.

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Monitoring the effectiveness of nanosecond laser for the treatment of port-wine stain patients using non-invasive imaging systems

A variety of lasers have been used to treat port-wine stain (PWS) birthmarks, however, all of them carry the risk of adverse effects. Our objective was to assess the effectiveness and safety of nanosecond (ns) laser treatment for PWS patients using non-invasive images. This study included 20 PWS patients, whose ages ranged from one to sixteen years. A nanosecond laser (λ=595 nm; τp=2 ns), with a spot size of 5 mm, and parameters of 0.2-0.3 J/cm2, 5 Hz, was used in three passes. The infrared thermal imager aided in determining the optimal laser dosage and preventing side effects. The primary efficiency was evaluated using a DermaSpectrometer, and patients were followed up after one week, four weeks, three months, and twelve months. The infrared thermal images of skin surface temperature assessment in the first ten seconds were recorded after the maximal energy density 0.3 J/cm2 treatment. The thermal wave equation and Penne’s bioheat transfer equation ranged from 32.4±0.1 to 33.8±0.2°C, 32.6±0.1 to 34.7±0.3°C (baseline skin surface temperature - 32.4±0.3°C) respectively. Transient hyperpigmentation appeared in 5% (n=1) of the 20 patients, but it resolved spontaneously within three months. There was no evidence of permanent hypopigmentation or scarring. The DermaSpectrometer revealed a 30% reduction in Hb-index three months after a single treatment. The infrared image instrument is helpful in determining the optimum laser dosage. For the treatment of PWS patients, a nanosecond pulsed laser at 595nm was effective and safe.

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Breast Carcinoma With Tubulopapillary Features Has a Distinct Immunophenotypic and Molecular Signature: A Report of Two Tumors and Literature Review.

Breast carcinoma with tubulopapillary features is a newly described entity associated with poor prognosis with only 14 tumors reported in the literature. We report 2 additional tumors and identify novel immunohistochemical and molecular features of the tumor. The first tumor was from a 72-year-old woman with nonmetastatic breast carcinoma and the second was from a 32-year-old woman with metastatic breast carcinoma who received neoadjuvant therapy. Both tumors had high-grade nuclear features with a distinctive morphology characterized by infiltrating open glands with intratubular papillary and micropapillary projections in >90% of the invasive carcinoma. In addition to the usual predictors of aggressive behavior, both tumors showed a high expression of p16 and SOX10, which has not been previously described. Targeted tumor sequencing revealed pathogenic variants of TP53 in both tumors, in agreement with previous reports. Prior studies have shown a correlation between p16 and SOX10 expression with high-grade features and worse prognosis; typically seen in triple-negative carcinomas as demonstrated in both of our tumors. However, not all reported tumors of breast carcinoma with tubulopapillary features have demonstrated a triple-negative profile as there are a few reports of tumors with estrogen receptor and/or human epidermal growth factor 2 expression. Due to their distinct morphologic and molecular characteristics, breast carcinoma with tubulopapillary features may represent a new breast cancer histologic subtype.

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A Biomarker of Stress and Self-reported Caregiving Distress Predict Poor Quality of Life in Family Caregivers of Patients With Heart Failure.

Family caregivers are at a high risk for low quality of life due to caregiving-related stress. Caregivers' stress is commonly assessed using self-reported measures, which reflect relatively subjective and long-term stress related to caregiving, but objective biological markers of stress are rarely used for caregivers. The purposes of this study were (1) to determine whether caregiver characteristics were associated with stress assessed using a stress biomarker (serum cortisol) and a self-reported caregiving distress measure (Caregiver Burden Inventory) and (2) to determine the predictability of both stress measures for quality of life in caregivers of patients with heart failure. Taiwanese family caregivers (N = 113; mean age, 54.5 years; 70.8% female) of patients with heart failure completed surveys including caregiving distress and quality of life measured by the Caregiver Burden Inventory and the Short Form-36 (physical and psychological well-being subscales), respectively, and provided blood samples for serum cortisol. Independent t tests, correlation, and hierarchical regression were conducted. Single caregivers had higher serum cortisol levels than married caregivers (P = .002). Men had significantly higher serum cortisol levels than women (P = .010), but men reported lower caregiving distress than women (P = .049). Both serum cortisol (β = -0.32, P = .012) and caregiving distress (β = -0.29, P = .018) were significant predictors of quality of life in the physical well-being scale while controlling for caregivers' characteristics and depressive symptoms. Serum cortisol (β = -0.28, P = .026) and caregiving distress (β = -0.25, P = .027) also predicted quality of life in the psychological well-being scale. Serum cortisol and self-reported caregiving distress have similar predictability for quality of life in family caregivers of patients with heart failure. Reducing stress and caregiving distress is critical to improving quality of life in this population.

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Short-term outcomes of intracorporeal delta-shaped overlap versus extracorporeal anastomosis after laparoscopic colectomy: a propensity score-matched cohort study

Abstract Background Laparoscopic colectomy methods, including intracorporeal anastomosis (IA), are commonly used in clinical practice and have become a research area. Previously, we described a novel IA technique, delta‑shaped overlap anastomosis (DOLA). This study aimed to describe detailed surgical tools for DOLA and their feasibility and safety by comparing short-term DOLA outcomes with those of conventional extracorporeal anastomosis (EA) after propensity score matching. Methods In total, 121 consecutive patients who underwent laparoscopic colectomy between June 2018 and August 2021 were retrospectively assessed. Linear staplers were used for all anastomoses. DOLA and EA groups included 46 and 74 patients, respectively. Propensity score matching analysis was conducted to compare matched groups based on clinicopathological characteristics, surgical and perioperative outcomes, complications, and postoperative inflammatory reactions. After matching, the DOLA and EA groups consisted of 35 cases each that were analyzed. Results Both groups had similar demographic characteristics, surgical procedures, histopathological outcomes, and postoperative complications. The DOLA group had significantly less blood loss than the EA group (10 versus 20 mL, p < 0.001). The DOLA group skin excision length (4 versus 6 cm, p < 0.001) and postoperative hospital stay length (6 versus 7 days, p < 0.001) were significantly shorter than those of the EA group. Increasing C-reactive protein (CRP) values at 1, 3, and 6 postoperative days were significantly lower in the DOLA group than in the EA group (p = 0.02, p = 0.03, and p = 0.04, respectively). Conclusions DOLA was significantly associated with lesser blood loss, shorter skin incision lengths, shorter postoperative hospital stays, and lower CRP level elevations than EA. DOLA is a safe, feasible technique that is potentially less invasive as compared to conventional EA.

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Chronic Hepatitis B, C, and stroke; association and pathophysiology

Background and Objectives:
 Hepatitis infection may raise the incidence of stroke and other cerebrovascular abnormalities, according to several studies. However, its association is controversial. This review looked to compile the most recent research on the relationship between HBV and HCV, atherosclerosis, and stroke.
 Methods:
 This article reviews the literature on the connection between hepatitis B and C viruses with stroke and atherosclerosis. The search included articles from PubMed, PakMediNet, and Google Scholar, as well as a Medline search using specific keywords and MeSH terms. A total of 2655 articles were identified. Out of these 2655 articles we identified 134 articles in English for review. These 134 articles comprised of original studies, individual case studies, and retrospective cohorts. The review included original research, individual case reports, and retrospective cohorts published after 1990. Studies addressing co-infection with HIV were excluded.
 Results:
 After the screening, many articles were selected which included several topics of discussion under the said heading. The studies were closely examined to gather pertinent information relevant to the review's objectives. Most of the literature emphasized the link between chronic hepatitis and the risk of stroke.
 Conclusion:
 Although current evidence does tilt the scale in favor of hepatitis-causing cerebrovascular disease, this review study has some limitations, such as the lack of prospective cohorts and limited evidence for the natural history of hepatitis patients in relation to cardiovascular and cerebrovascular diseases.

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