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In patients with unresectable hepatocellular carcinoma (HCC), the advances in direct-acting antiviral (DAA) therapy for chronic hepatitis C remain unclear. We aimed to investigate the characteristics of DAA therapy, when compared to interferon (IFN) therapy.

In this hospital-based study, all HCC patients in Barcelona Clinic Liver Cancer (BCLC) stage B or C, who received pegylated IFN or DAA, were retrospectively screened from 2009 to 2020. Doxorubicin nmr Patients without viremia, without HCC, or with HCC in BCLC stage 0, A, or D prior to antiviral therapy, were excluded. Rates of, and odds ratio (OR) for sustained virological response (SVR) achievement were analyzed.

Nineteen and 78 patients were recruited into the IFN and DAA groups, respectively. The median age was significantly older in the DAA group (DAA vs. IFN 69.5 [25%-75% IQR 62.8-77.3] vs. 64.0 [25%-75% IQR 61.0-68.0]; p< 0.05). The SVR rates were higher in the DAA group as per protocol (DAA vs. IFN 94.5% vs. 76.5%; p< 0.05) and in BCLC stage B (DAA vs. IFN 95.2% vs. 76.5%; p< 0.05). All patients in BCLC stage C received DAA therapy, with the SVR rate being 90.9%. In multivariable regression analysis, the 4-week virological response (OR 5.6, 95% CI 1.3-25.4) and HCC within the up-to-7 criteria (OR 3.7, 95% CI 1.1-12.9) were independent factors associated with SVR (all p< 0.05).

Compared to IFN therapy, more elderly patients with unresectable HCCs were able to receive DAA therapy, while achieving a significantly higher SVR rate.

Compared to IFN therapy, more elderly patients with unresectable HCCs were able to receive DAA therapy, while achieving a significantly higher SVR rate.

Fetal supraventricular tachycardia is a relatively uncommon cardiac rhythm abnormality which is often associated with adverse perinatal outcomes if untreated. Although there are several treatment modalities and protocols in use globally, there is no consensus as to the most effective antiarrhythmic to manage this condition.

This study aimed to evaluate perinatal outcomes following prenatal maternal therapy for fetal supraventricular tachycardia.

This was a 20-year retrospective cohort study. Institutional records were reviewed for antenatal therapy choice and maternal and fetal outcomes.

Sixty-nine cases met diagnostic criteria for fetal SVT, of which 56 (81%) received maternal antiarrhythmic therapy. Digoxin was the most common, but least effective, first-line therapy in 28 patients, achieving successful rate reversion in 35.7%. Thirty-one patients (55%) required second-line therapy, and this was most successful with digoxin and flecainide polytherapy achieving rate reversion in 17 of 18 cases (94.5%) at a median of 3 days (1.5-7). Hydrops was present in 23 (33%) cases at initial presentation, 16 of which achieved rate reversion. There was minimal difference in treatment efficacy comparing single- or multiple-agent treatment in the setting of hydrops (50% vs. 42.8%). Side effects occurred in 14/56 treated patients (25%) but were severe in only 8 (14.3%) women, most commonly with digoxin and flecainide polytherapy (6 of 8 cases). There were 3 (4%) fetal deaths amongst the study cohort.

Digoxin and flecainide polytherapy were well tolerated and successfully achieved rhythm and rate control in fetuses with prenatally diagnosed supraventricular tachycardia. The presence of hydrops was a poor prognostic feature.

Digoxin and flecainide polytherapy were well tolerated and successfully achieved rhythm and rate control in fetuses with prenatally diagnosed supraventricular tachycardia. The presence of hydrops was a poor prognostic feature.

Heart failure (HF) is one of the main comorbidities in patients receiving maintenance hemodialysis (HD). Sacubitril/valsartan (SAC/VAL) is widely used in HF patients with reduced ejection fraction (HFrEF) or HF mid-range ejection fraction (HFmrEF). However, the pharmacokinetic (PK) and pharmacodynamic properties of SAC/VAL in HD patients with HF remain uncertain.

This study aimed to analyze the efficacy and PK properties of SAC/VAL in HD patients with HFrEF or HFmrEF.

HD patients with HFrEF or HFmrEF were treated with SAC/VAL 50 or 100 mg twice a day (BID) and the concentrations of valsartan and LBQ657 (active metabolite of SAC) were determined by high-performance liquid chromatography-tandem mass spectrometry during HD and on the days between HD sessions (interval days). N-terminal-pro B-type natriuretic peptide and high-sensitivity troponin T were measured, and left ventricular ejection fraction (LVEF) was evaluated by echocardiography.

The mean maximum plasma concentrations (Cmax) of LBQ657 and VAL on the interval days were 15.46 ± 6.01 and 2.57 ± 1.23 mg/L, respectively. Compared with previous values in patients with severe renal impairment and healthy volunteers, these levels both remained within the safe concentration ranges during treatment with SAC/VAL 100 mg BID. Moreover, SAC/VAL significantly improved LVEF in HD patients with HFrEF or HFmrEF (p < 0.05).

HD did not remove the SAC metabolite LBQ657 or VAL in patients with HF. However, SAC/VAL 100 mg BID was safe and effective in patients undergoing HD.

HD did not remove the SAC metabolite LBQ657 or VAL in patients with HF. However, SAC/VAL 100 mg BID was safe and effective in patients undergoing HD.In this article, we present holistic and person-centered perspectives in psychiatry, with the aim of better understanding what a focus on personhood might really mean and what clinical implications it might have. We first introduce classical and philosophical concepts of personhood, in order to then outline person-centered approaches in psychiatry, which mainly focus on the person of the patient. We then argue that, for it to really be person-centered, psychiatry must necessarily also focus on the person of professionals. We thus explore the notion of stance, as the expression of the therapist's personhood. By unpacking the effects that a professional's stance can have on patients, we finally turn to a consideration of the interpersonal sphere. More specifically, we propose clinical considerations on a therapeutic stance that strives to support and to help the person of the patient unfold. Such a stance must - we argue - necessarily be a dialogical one. Drawing on these considerations, we thus claim that a truly person-centered approach in psychiatry must necessarily and automatically be interperson-centered and dialogical. In the concluding remarks, we finally discuss broader societal implications and outline future research perspectives.

Leg ulcers are a frequent complication in patients with the inherited hemoglobin disorders. In thalassemia, the literature is limited, and factors associated with the development of leg ulcers in HbE beta thalassemia, the most common form of severe beta thalassemia worldwide, have not previously been reported.

We reviewed all available medical records of patients with HbE beta thalassemia to document the onset of leg ulcers at the two largest treatment centres in Sri Lanka. We reviewed the literature to identify studies reporting outcomes of interventions for ulcers in severe thalassemia.

Of a total of 255 actively registered patients with HbE thalassemia in the two centres, 196 patient charts were evaluable. A leg ulcer with a documented date of onset was recorded in 45 (22%) of 196 evaluable patients, aged (mean ± SEM) 22.2 ± 1.4 years. Most had been irregularly transfused; steady state hemoglobin was 6.4 ± 0.2 g/dL. Treatment achieving healing in 17 patients included transfusions, antibiotics, oral zinc, wound toileting and skin grafting.

Leg ulcers may be more common in HbE beta thalassemia than in other forms of thalassemia. A systematic approach to treatment will be needed to document the prevalence and factors placing such patients at risk for leg ulcers. Controlled trials to evaluate the optimal treatment of this common complication are indicated.

Leg ulcers may be more common in HbE beta thalassemia than in other forms of thalassemia. A systematic approach to treatment will be needed to document the prevalence and factors placing such patients at risk for leg ulcers. Controlled trials to evaluate the optimal treatment of this common complication are indicated.

Numerous studies reported poorer outcomes for patients who were admitted at weekends or off-hour, which relates to the underlying concept called the "weekend effect." We aimed to assess the effect of adverse outcomes in older patients with intertrochanteric fracture surgery.

A retrospective cohort study of patients aged ≥65 years with intertrochanteric fracture surgery. Data were collected from computerized medical records and all patients had a long-term follow-up. The association between weekend effect with adverse outcomes and factors for all-cause mortality was studied by 3-group comparison, Spearman and partial correlation analysis, univariate analysis, and multivariate Cox proportional-hazard model.

Our results showed no evidence supporting the existence of a weekend effect on adverse outcomes, including mortality rates (p = 0.950, log-rank), length of hospital stay, total hospital costs, rate and volume of transfusion, visual analog scale score, Harris Hip Score, and specific complications (all per patients with intertrochanteric fractures on any day of the week.The development of sexually dimorphic gonads is a unique process that starts with the specification of the bipotential genital ridges and culminates with the development of fully differentiated ovaries and testes in females and males, respectively. Research on sex determination has been mostly focused on the identification of sex determination genes, the majority of which encode for proteins and specifically transcription factors such as SOX9 in the testes and FOXL2 in the ovaries. Our understanding of which factors may be critical for sex determination have benefited from the study of human disorders of sex development (DSD) and animal models, such as the mouse and the goat, as these often replicate the same phenotypes observed in humans when mutations or chromosomic rearrangements arise in protein-coding genes. Despite the advances made so far in explaining the role of key factors such as SRY, SOX9, and FOXL2 and the genes they control, what may regulate these factors upstream is not entirely understood, often resulting in the inability to correctly diagnose DSD patients. The role of non-coding DNA, which represents 98% of the human genome, in sex determination has only recently begun to be fully appreciated. In this review, we summarize the current knowledge on the long-range regulation of 2 important sex determination genes, SOX9 and FOXL2, and discuss the challenges that lie ahead and the many avenues of research yet to be explored in the sex determination field.Scientists have long struggled to establish how larger brains translate into higher cognitive performance across species. While absolute brain size often yields high predictive power of performance, its positive correlation with body size warrants some level of correction. It is expected that larger brains are needed to control larger bodies without any changes in cognitive performance. Potentially, the mean value of intraspecific brain-body slopes provides the best available estimate for an interspecific correction factor. For example, in primates, including humans, an increase in body size translates into an increase in brain size without changes in cognitive performance. Here, we provide the first evaluation of this hypothesis for another clade, teleost fishes. First, we obtained a mean intraspecific brain-body regression slope of 0.46 (albeit a relatively large range of 0.26 to 0.79) from a dataset of 51 species, with at least ten wild adult specimens per species. This mean intraspecific slope value (0.46) is similar to that of the encephalisation quotient reported for teleost (0.

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