The efficacy of daily snack replacement with oligofructose-enriched granola bars in overweight and obese adults: a 12-week randomised controlled trial.

Oligofructose is a prebiotic dietary fibre obtained from chicory root inulin. Oligofructose supplementation may affect satiety, food intake, body weight and/or body composition. The aim was to examine the efficacy of oligofructose-supplemented granola bars on the following weight management outcomes: satiety, energy intake, body weight and body composition in overweight or obese adults. In all, fifty-five adults with overweight or obesity (thirty-six females/nineteen males; age: 41 (sd 12) years; 90·6 (sd 11·8) kg; BMI: 29·4 (sd 2·6) kg/m2) participated in a parallel, triple-blind, placebo-controlled intervention. A total of twenty-nine subjects replaced their snacks twice a day with an equienergetic granola bar supplemented with 8 g of oligofructose (OF-Bar). Subjects in the control group (n 26) replaced their snack with a control granola bar without added oligofructose (Co-Bar). Satiety, 24-h energy intake, body weight and body composition (fat mass and waist circumference) were measured at baseline, weeks 6 and 12. In addition, weekly appetite and gastrointestinal side effects were measured. During the intervention, energy intake, body weight and fat mass remained similar in the Co-Bar and OF-Bar groups (all P>0·05). Both groups lost 0·3 (sd 1·2) kg lean mass (P<0·01) and reduced their waist circumference with -2·2 (sd 3·6) cm (P<0·0001) after 12 weeks. The OF-Bar group reported decreased hunger in later weeks of the intervention (P=0·04), less prospective food consumption (P=0·03) and less thirst (P=0·003). To conclude, replacing daily snacks for 12 weeks with oligofructose-supplemented granola bars does not differentially affect energy intake, body weight and body composition compared with a control bar. However, there was an indication that appetite was lower after oligofructose bar consumption.

Changing paradigms in bioequivalence trials submitted to the EMA for evaluation - A clinical and regulatory perspective.

BACKGROUND: The selection of a robust bioequivalence (BE) study designs for registering a generic product remains still a hard task. This task is still challenging despite the fact that generic products are much needed by health care providers in economical terms. Thus, BE study designs could be a means to allow companies to reduce costs and reach the market earlier. We therefore investigated whether different approaches in various products assessed by the European Medicines Agency during the approval phase resulted in a reduction in resources required to show bioequivalence for different medicinal products. METHODS: European Public Assessment Reports (EPARs) for off-patent medicinal products authorised within the European Union (EU) through the centralised procedure during the period 2007-2015 were retrieved and reviewed to identify the clinical studies that resulted in fewer number of subjects, the number of centres or trial duration versus the two-period crossover design. RESULTS: 7 studies out of 108 were considered as having benefitted from having a different design. Differences noted included having a different dose allocation scheme, having a different number of dosing periods, having a different number of treatment arms, and having one study evaluating different strengths. Benefits noted included a decrease in the number of subjects and centres required, decreases in study duration and a reduced number of studies required to demonstrate bioequivalence. CONCLUSION: Bioequivalence studies can be designed in a specific manner to require fewer resources to carry out. Fewer resources required to register a medicinal product, could impart an advantage to companies (such as to be first on the market) or could even translate to making medicines more accessible (such as cheaper) to patients.

Pledgeted versus nonpledgeted sutures in aortic valve replacement: Insights from a prospective multicenter trial.

Objective: The objective of this study was to compare short- and midterm clinical and echocardiographic outcomes according to the use of pledgeted sutures during aortic valve replacement. Methods: Patients with aortic stenosis or regurgitation requiring aortic valve replacement were enrolled in a prospective cohort study to evaluate the safety of a new stented bioprosthesis. Outcomes were analyzed according to the use of pledgets (pledgeted group) or no pledgets (nonpledgeted group). The primary outcome was a composite of thromboembolism, endocarditis, and major paravalvular leak at 5 years of follow-up. Secondary outcomes included multiple clinical endpoints and hemodynamic outcomes. Propensity score matching was performed to adjust for prognostic factors, and subanalyses with small valve sizes (<23 mm) and suturing techniques were performed. Results: The pledgeted group comprised 640 patients (59%), and the nonpledgeted group 442 (41%), with baseline discrepancies in demographic characteristics, comorbidities, and stenosis severity. There were no differences between groups in any outcome. After propensity score matching, the primary outcome occurred in 41 (11.7%) patients in the pledgeted and 36 (9.8%) in the nonpledgeted group (P = .51). The effective orifice area was smaller in the pledgeted group (P = .045), whereas no difference was observed for the mean or peak pressure gradient. Separate subanalyses with small valve sizes and suturing techniques did not show relevant differences. Conclusions: In this large propensity score-matched cohort, comprehensive clinical outcomes were comparable between patients who underwent aortic valve replacement with pledgeted and nonpledgeted sutures up to 5 years of follow-up, but pledgets might lead to a slightly smaller effective orifice area in the long run.

Factors impacting survival after transarterial radioembolization in patients with hepatocellular carcinoma: Results from the prospective CIRT study.

Background & Aims: Transarterial radioembolization (TARE) with Yttrium-90 resin microspheres is an established treatment option for patients with hepatocellular carcinoma (HCC). However, optimising treatment application and patient selection remains challenging. We report here on the effectiveness, safety and prognostic factors, including dosing methods, associated with TARE for HCC in the prospective observational CIRT study. Methods: We analysed 422 patients with HCC enrolled between Jan 2015 and Dec 2017, with follow-up visits every 3 months for up to 24 months after first TARE. Patient characteristics and treatment-related data were collected at baseline; adverse events and time-to-event data (overall survival [OS], progression-free survival [PFS] and hepatic PFS) were collected at every 3-month follow-up visit. We used the multivariable Cox proportional hazard model and propensity score matching to identify independent prognostic factors for effectiveness outcomes. Results: The median OS was 16.5 months, the median PFS was 6.1 months, and the median hepatic PFS was 6.7 months. Partition model dosimetry resulted in improved OS compared to body surface area calculations on multivariable analysis (hazard ratio 0.65; 95% CI 0.46-0.92; p = 0.0144), which was confirmed in the exact matching propensity score analysis (hazard ratio 0.56; 95% CI 0.35-0.89; p = 0.0136). Other independent prognostic factors for OS were ECOG-performance status >0 (p = 0.0018), presence of ascites (p = 0.0152), right-sided tumours (p = 0.0002), the presence of portal vein thrombosis (p = 0.0378) and main portal vein thrombosis (p = 0.0028), ALBI grade 2 (p = 0.0043) and 3 (p = 0.0014). Adverse events were recorded in 36.7% of patients, with 9.7% of patients experiencing grade 3 or higher adverse events. Conclusions: This large prospective observational dataset shows that TARE is an effective and safe treatment in patients with HCC. Using partition model dosimetry was associated with a significant improvement in survival outcomes. Impact and implications: Transarterial radioembolization (TARE) is a form of localised radiation therapy and is a potential treatment option for primary liver cancer. We observed how TARE was used in real-life clinical practice in various European countries and if any factors predict how well the treatment performs. We found that when a more complex but personalised method to calculate the applied radiation activity was used, the patient responded better than when a more generic method was used. Furthermore, we identified that general patient health, ascites and liver function can predict outcomes after TARE. Clinical trial number: NCT02305459.

Interleukin Levels and Non-Alcoholic Fatty Liver Disease in Chronic Plaque Psoriasis: An Analytical Case Control Study.

Background: Psoriasis is a chronic, immune mediated inflammatory condition of the skin and imbalance in inflammatory mediators could result in insulin resistance, metabolic syndrome and facilitate the occurrence and progression of Non-alcoholic fatty liver disease (NAFLD). Objectives: Primary objectives: To study the frequency of NAFLD in cases of chronic plaque psoriasis and controlsTo study the interleukin levels in cases of chronic plaque psoriasis and controls. Secondary objectives: To study the BMI, lipid profile, waist circumference, FBS (fasting blood sugar), PPBS (post prandial blood sugar) and serum insulin in cases and controlsTo study the association of age, duration of psoriasis, PASI (psoriasis area severity index), BSA (body surface area) involved, BMI (body mass index), lipid profile, obesity, waist circumference, FBS (fasting blood sugar), PPBS (post prandial blood sugar) and serum insulin levels with NAFLD in patients of chronic plaque psoriasisTo correlate serum levels of IL1-ß, IL6 and TNF-α with NAFLD in patients of chronic plaque psoriasis. Methods: 50 clinically diagnosed cases of chronic plaque psoriasis with age ≥ 18years, diseases duration ≥ 6 months and 30 age and sex matched controls were recruited. PASI, BSA of cases was calculated and BMI, BP, WC of all subjects was measured. Serum lipid profile, FBS, PPBS, insulin level, IL1- ß , IL6, TNF- α , high frequency B-mode ultrasound, LFT and fibroscan were done in all subjects. Results: 28(56.0%) cases and 2(6.6%) controls had NAFLD with statistically significant difference. Significantly elevated WC, serum insulin, deranged lipid profile, fatty liver, transaminitis, fibroscan score, liver fibrosis, NAFLD and interleukins were found in cases vs controls. There was a significant association of NAFLD in psoriatic patients with increasing duration of psoriasis, BMI ≥23 Kg/m2, high WC, increasing BSA involved, deranged lipid profile, raised total cholesterol levels and increasing number of risk factors. Nonsignificant but positive association of NAFLD in cases was found with high levels of IL1 - ß, IL - 6, TNF-α, FBS and increasing PASI. Conclusion: Significantly increased interleukin levels and their weak positive correlation with the severity of psoriasis (PASI, BSA) in patients of chronic plaque psoriasis explains the possible role of inflammation in the causation of psoriasis. Screening may be considered in psoriatic patients with increasing duration of psoriasis, high WC, high BSA involved, high BMI, obesity, dyslipidemia and insulin resistance. Limitations: Small sample size. Conflict of Intrest: NONE.

The Association Between Chronic Plaque Psoriasis and Nonalcoholic Fatty Liver Disease in Indian Patients: Results of a Pilot Study.

Background: Psoriasis is a chronic dermatosis with potential to cause systemic disease by triggering dysmetabolism, such as metabolic syndrome and nonalcoholic fatty liver disease (NAFLD). We studied the relationship and associations between NAFLD and clinical features, including age, gender, disease duration, and severity of psoriasis in our patients. Methods: This cross-sectional study comprised 61 (m:f, 43:19) patients without pre-existing comorbidities and matched 24 (m:f, 16:8) healthy controls aged between 20 and 68 years. Disease severity was graded as mild, moderate, and severe by psoriasis area and severity index score and body surface area (BSA) involvement. The grades of fatty liver and liver fibrosis were assessed using liver ultrasonography (USG) and transitional vibration-controlled elastography (Fibroscan). Results: Overall, 67.2% of patients were aged >40 years, and the duration of disease was <5years in 60.7% of patients. Mild and moderate to severe psoriasis occurred in 78.7% and 21.3% of patients, respectively. BSA was >10% in 57.5% patients. The proportion of NAFLD was 27.9% and 32.8% by USG and Fibroscan compared with 20.8% in controls. Statistically, there was no significant difference or association between the prevalence of NAFLD among patients and controls, and gender, age (mean ± standard deviation, 47.5 ± 13.8 vs. 45.2 ± 15.7), duration, severity of psoriasis, and arthritis between psoriatic patients with and without NAFLD. Conclusion: This was a pilot study because of the numerosity of sample and highlights trends for possible link between psoriasis and NAFLD, but the results need cautious interpretation and clinical application. Whether NAFLD can be attributed to overall systemic inflammatory process of psoriasis or it occurs as an epiphenomenon of concurrent metabolic syndrome needs elucidation with well-designed studies. Cross-sectional study design, small number of patients, and controls remain major limitations. The study did not compare its findings with liver biopsy.

Halobetasol propionate lotion 0.05% in patients 12 to 16 years 11 months of age with plaque psoriasis: Results of an open-label study evaluating adrenal suppression potential.

BACKGROUND: The effects of halobetasol propionate (HBP) lotion 0.05% on the hypothalamic-pituitary-adrenal (HPA) axis have not been previously evaluated in adolescents. OBJECTIVE: To examine the effect of HBP on HPA axis suppression in patients aged <17 years with plaque psoriasis. METHODS: In this phase 4, open-label, multicenter study, patients aged 12 to 16 years 11 months with stable plaque psoriasis covering ≥10% of their body surface area were enrolled. The patients applied an HBP lotion twice daily for up to 2 weeks. The cosyntropin stimulation test was used to determine cortisol levels at the time of screening and at the end of the study to evaluate HPA axis response. The additional endpoints included adverse events, disease severity (measured using Investigator Global Assessment score), and percent body surface area affected. RESULTS: Sixteen patients were enrolled and included in the safety population; 14 were included in the evaluable population. One patient exhibited an abnormal HPA axis response (16.2 µg/dL) at the end of the study; the response returned to normal at the 6-month follow-up visit. By the end of the study, the Investigator Global Assessment score improved by ≥1 point in most patients; moreover, the percent body surface area affected decreased from 11.5% to 2.8%. One mild adverse event was possibly related to the HBP lotion; however, it resolved and did not cause study discontinuation. LIMITATIONS: Small sample size. CONCLUSION: The HBP lotion 0.05% appeared efficacious and well tolerated in patients as young as 12 years old.

Rapid cooling is a safe technique in patients undergoing circulatory arrest for aortic repair.

Objective: To evaluate our institutional experience with rapid cooling for hypothermic circulatory arrest in proximal aortic repair. Methods: We retrospectively reviewed data from 2171 patients who underwent proximal aortic surgery requiring hypothermic circulatory arrest between 1991 and 2020. Cooling times were divided into quartiles and clinical outcome event rates were compared across quartiles using contingency table methods. Incremental effect of cooling time was assessed in the context of other perfusion time variables using multiple logistic regression analysis. Results: Median age was 61 years (interquartile range, 49-70 years) and 34.1% of patients were women. The procedure was emergent in 33.5% of patients, 22.9% had a previous sternotomy. The median circulatory arrest time was 22 minutes, with retrograde cerebral perfusion used in 94% of cases. Median cardiopulmonary bypass time was 149 minutes, with an aortic crossclamp time of 90 minutes. Patients were cooled to deep hypothermia. The first quartile had cooling times ranging from 5 to 13 minutes, second 14 to 18 minutes, third 19-23 minutes, and fourth 24-81 minutes. Overall, 30-day mortality was 9.4%, and was not significantly different across quartiles. There was a statistically significant trend toward lower rates of postoperative encephalopathy, gastrointestinal complications, and respiratory failure with shorter cooling times (P < .001, .006, and < .001, respectively). There was no significant difference in rates of postoperative stroke or dialysis. Conclusions: Rapid cooling can be performed safely in patients undergoing aortic surgery requiring circulatory arrest without increasing mortality or stroke. There were significantly lower rates of coagulopathy, respiratory failure, and postoperative encephalopathy with shorter cooling times.

Magnitude and associated factors of unplanned extubation in intensive care unit: A multi-center prospective observational study.

Background: Unplanned extubation is the removal of an endotracheal tube accidently during procedural activities or by the action of the patient. It is one of the commonly reported complications among mechanically ventilated patients in the intensive care unit. This study aimed to assess the magnitude and associated factors of unplanned extubation in intensive care units at referral hospitals in Addis Ababa, Ethiopia, 2021. Methods: Institutional based prospective observational study was conducted on 317 intubated patients in the intensive care unit at referral hospitals of Addis Ababa, Ethiopia, from January 8, 2021-May 9, 2021. Data were collected using a structured questionnaire. Descriptive statics were expressed in percentages and presented with tables and figures. Both Bivariable and multivariable logistic analysis was done to identify factors associated with unplanned extubation in intensive care unit. P < 0.05 with 95% CI was set as Statistical significance. Result: The prevalence of unplanned extubation in this study was 19.74%. Being male (AOR = 3.132, 95%CI: 1.276-7.69), duration of intubation <5days (AOR = 2.475, 95% CI: 1.039-5.894), managed by junior resident (AOR = 5.25, 95% CI: 2.125-12.969), being physically restrained (AOR = 4.356, 95%CI: 1.786-10.624), night shift (AOR = 3.282, 95%CI:1.451-7.424)and agitation (AOR = 4.934,95%CI:1.934-12.586) were significantly contribute to the occurrence of unplanned extubation. Conclusion: and recommendation: This study showed that the prevalence of unplanned extubation was high in the intensive care unit. We suggest to intensive care unit staff to give special attention to early intubated patients, especially male individuals and the stakeholders of hospitals should rearrange the time of shift and physician schedules in the intensive care unit.

Postoperative atrial fibrillation and atrial epicardial fat: Is there a link?

Background: Atrial Epicardial Adipose Tissue (EAT) is presumably involved in the pathogenesis of atrial fibrillation (AF). The transient nature of postoperative AF (POAF) suggests that surgery-induced triggers provoke an unmasking of a pre-existent AF substrate. The aim is to investigate the association between the volume of EAT and the occurrence of POAF. We hypothesise that the likelihood of developing POAF is higher in patients with high compared to low left atrial (LA) EAT volumes. Methods: Quantification of LA EAT based on the Hounsfield Units using custom made software was performed on pre-operative coronary computed tomography angiography scans of patients who underwent cardiac surgery between 2009 and 2019. Patients with mitral valve disease were excluded. Results: A total of 83 patients were included in this study (CABG = 34, aortic valve = 33, aorta ascendens n = 7, combination n = 9), of which 43 patients developed POAF. The EAT percentage in the LA wall nor indexed EAT volumes differed between patients with POAF and with sinus rhythm (all P > 0.05). In multivariable analysis, age and LA volume index (LAVI) were the only independent predictors for early POAF (OR: 1.076 and 1.056, respectively). Conclusions: As expected, advanced age and LAVI were independent predictors of POAF. However, the amount of local EAT was not associated with the occurrence of AF after cardiac surgery. This suggests that the role of EAT in POAF is rather limited, or that the association of EAT in the early phase of POAF is obscured by the dominance of surgical-induced triggers.

Echocardiographic Investigation of Low-Flow State in a Hispanic/Latino Population.

Objective: To assess the prevalence of low-flow state (LFS) with left ventricular (LV) stroke volume index of less than 35 mL/m2 and the demographics, clinical and echocardiographic characteristics associated with LV remodeling and function in a Hispanic/Latino population. Participants and Methods: The study included 1346 asymptomatic participants from the Hispanic Community Health Study/Study of Latinos with normal LV ejection fraction (≥55%) and no valvular heart disease. LV volume, mass and left atrial volume, LV ejection fraction, global longitudinal strain, and myocardial contraction fraction were measured by echocardiography. The participants were divided into LFS or normal flow state (NFS: stroke volume index ≥35 mL/m2). Demographics, clinical and echocardiographic characteristics, and measures of LV remodeling and function were compared between the LFS and NFS groups. Results: The prevalence of LFS was 41%. In comparison with NFS, the LFS had lower LV mass index (77.2±0.96 g/m2 vs 84.6±0.86 g/m2; P<.001), left atrial volume index (20.6±0.35 mL/m2 vs 23.5±0.37 mL/m2; P<.001), global longitudinal strain (-16.8±0.16% vs -17.7±0.17%; P<.001), and myocardial contraction fraction (43.3±0.63% vs 55.7±0.64%; P<.001). There was no significant difference in the relative wall thickness (LFS: 0.40±0.004 vs NFS: 0.40±0.005; P=.57). The LFS group had significantly higher hemoglobin A1c (6.18±0.07% vs 5.97±0.04%; P=.01) than the NFS group. Conclusion: A high prevalence of LFS associated with echocardiographic characteristics reflecting unfavorable LV remodeling and function was observed in a Hispanic/Latino population. Further studies of the prognostic significance of LFS in a large multiethnic population are warranted.

Comparison Between Bicuspid and Tricuspid Aortic Regurgitation: Presentation, Survival, and Aorta Complications.

Background: Although the Asian population is growing globally, data in Asian subjects regarding differences between bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) in aortic regurgitation (AR) remain unexplored. Objectives: The aim of this study was to examine differences between Asian BAV-AR and TAV-AR in significant AR, including aorta complications. Methods: The study included 711 consecutive patients with chronic moderate to severe and severe AR from 2008 to 2020. Outcomes included all-cause death, aortic valve surgery (AVS), and incidence of aortic dissection (AD). Results: There were 149 BAV-AR (mean age: 48 ± 16 years) and 562 TAV-AR (mean age: 68 ± 15 years; P < 0.0001) patients; baseline indexed left ventricle and indexed aorta size were larger in TAV-AR. Total follow-up was 4.8 years (IQR: 2.0-8.4 years), 252 underwent AVS, and 185 died during follow-up; 18 cases (only 1 BAV) of AD occurred, with a mean maximal aorta size of 60 ± 9 mm. The 10-year AVS incidence was higher in TAV-AR (51% ± 4%) vs BAV-AR (40% ± 5%) even after adjustment for covariates (P < 0.0001). The 10-year survival was higher in BAV-AR (86% ± 4%) vs TAV-AR (57% ± 3%; P < 0.0001) and became insignificant after age adjustment (P = 0.33). Post-AVS 10-year survival was 93% ± 5% in BAV-AR and 78% ± 5% in TAV-AR, respectively (P = 0.08). The 10-year incidence of AD was higher in TAV-AR (4.8% ± 1.5%) than in BAV-AR (0.9% ± 0.9%) and was determined by aorta size ≥45 mm (P ≤ 0.015). Compared with an age- and sex-matched population in Taiwan, TAV-AR (HR: 3.1) had reduced survival (P < 0.0001). Conclusions: Our findings suggest that TAV-AR patients were at a later stage of AR course and had a high AD rate as opposed to BAV-AR patients in Taiwan, emphasizing the importance of early referral for timely management. Surgery on the aorta with a lower threshold in TAV-AR should be considered.

Patterns of cardiovascular magnetic resonance inflammation in acute myocarditis from South Asia and Middle East.

Background: Cardiovascular magnetic resonance (CMR) is the test of choice for diagnosis and risk stratification of myocardial inflammation in acute viral myocarditis. The objective of this study was to assess patterns of CMR inflammation in a cohort of acute myocarditis patients from Northern Africa, Asia, and the Middle East using unsupervised machine learning. Methods: A total of 169 racially and ethnically diverse adults ( ≥ 18 years of age) with CMR confirmed acute myocarditis were studied. The primary outcome was a combined clinical endpoint of cardiac death, arrhythmia, and dilated cardiomyopathy. Machine learning was used for exploratory analysis to identify patterns of CMR inflammation. Results: Our cohort was diverse with 25% from Northern Africa, 33% from Southern Asia, and 28% from Western Asia/the Middle East. Twelve patients met the combined clinical endpoint - 3 had arrythmia, 8 had dilated cardiomyopathy, and 1 died. Patients who met the combined endpoint had increased anterior (p = 0.034) and septal (p = 0.042) late gadolinium enhancement (LGE). Multivariable logistic regression, adjusted for age, gender, and BMI, found that patients from Southern Asia (p = 0.041) and the Middle East (p = 0.043) were independently associated with lateral LGE. Unsupervised machine learning and factor analysis identified two distinct CMR patterns of inflammation, one with increased LGE and the other with increased myocardial T1/T2. Conclusions: We found that anteroseptal inflammation is associated with worsened outcomes. Using machine learning, we identified two patterns of myocardial inflammation in acute myocarditis from CMR in a racially and ethnically diverse group of patients from Southern Asia, Northern Africa, and the Middle East.

Time-Velocity Integral of Left Ventricular Outflow Tract Predicts Worse Long-Term Survival in Pulmonary Arterial Hypertension.

Background: The time-velocity integral of the left ventricular outflow tract (TVILVOT) has been demonstrated to correlate with heart failure hospitalization and mortality, but the association of TVILVOT with the severity and prognosis of pulmonary arterial hypertension (PAH) has not been evaluated. Objectives: The aim of this study was to investigate the predictive value of baseline TVILVOT in PAH. Methods: A total of 225 consecutive patients with a diagnosis of incident PAH were prospectively studied and echocardiology-derived TVILVOT was measured at enrollment followed by right heart catheterization examination within 48 hours. Cox proportional hazards analysis was performed to assess the association between baseline variables and mortality. Results: During a median follow-up period of 33.8 months, 44 patients died of cardiovascular events. Baseline TVILVOT was significantly lower in the nonsurvivors compared with the survivors (P < 0.001). Baseline TVILVOT was positively correlated with stroke volume obtained by right heart catheterization (r = 0.709; P < 0.001), and inversely correlated with N-terminal pro-B-type natriuretic peptide (r = -0.533; P < 0.001), pulmonary vascular resistance (r = -0.423; P < 0.001). Multivariate analysis showed that baseline TVILVOT (hazard ratio: 0.856; 95% CI: 0.780-0.941; P = 0.001) was an independent predictor of cardiovascular mortality in PAH. Patients with a baseline TVILVOT <17.1 cm (median value) had a significantly worse survival than those with a baseline TVILVOT ≥17.1 cm (P < 0.001). Conclusions: The findings of this study suggest that noninvasive TVILVOT provides a practical method to assess the severity and predict long-term outcome of PAH.

Immunohistochemical analyses of paraffin-embedded sections after primary surgery or trimodality treatment in esophageal carcinoma.

Background: The microscopic tumor extension before, during or after radiochemotherapy (RCHT) and its correlation with the tumor microenvironment (TME) are presently unknown. This information is, however, crucial in the era of image-guided, adaptive high-precision photon or particle therapy. Materials and methods: In this pilot study, we analyzed formalin-fixed paraffin-embedded (FFPE) tumor resection specimen from patients with histologically confirmed squamous cell carcinoma (SCC; n = 10) or adenocarcinoma (A; n = 10) of the esophagus, having undergone neoadjuvant radiochemotherapy followed by resection (NRCHT + R) or resection (R)]. FFPE tissue sections were analyzed by immunohistochemistry regarding tumor hypoxia (HIF-1α), proliferation (Ki67), immune status (PD1), cancer cell stemness (CXCR4), and p53 mutation status. Marker expression in HIF-1α subvolumes was part of a sub-analysis. Statistical analyses were performed using one-sided Mann-Whitney tests and Bland-Altman analysis. Results: In both SCC and AC patients, the overall percentages of positive tumor cells among the five TME markers, namely HIF-1α, Ki67, p53, CXCR4 and PD1 after NRCHT were lower than in the R cohort. However, only PD1 in SCC and Ki67 in AC showed significant association (Ki67: p = 0.03, PD1: p = 0.02). In the sub-analysis of hypoxic subvolumes among the AC patients, the percentage of positive tumor cells within hypoxic regions were statistically significantly lower in the NRCHT than in the R cohort across all the markers except for PD1. Conclusion: In this pilot study, we showed changes in the TME induced by NRCHT in both SCC and AC. These findings will be correlated with microscopic tumor extension measurements in a subsequent cohort of patients.

Left atrial, pulmonary vein, and left atrial appendage anatomy in Indigenous individuals: Implications for atrial fibrillation.

BACKGROUND: Indigenous Australians experience a greater burden of AF. Whether this is in-part due to differences in arrhythmogenic structures that appear to contribute to AF differences amongst other ethnicities is not known. METHODS: We studied forty individuals matched for ethnicity and other AF risk factors. Computed tomography imaging was used to characterise left atrial (LA), pulmonary vein (PV), and left atrial appendage (LAA) anatomy. RESULTS: There were no significant differences in LA diameters or volumes between Indigenous and non-Indigenous Australians. Similarly, we could not detect any consistent differences in PV number, morphology, diameters, or ostial characteristics according to ethnicity. LAA analyses suggested that Indigenous Australians may have a greater proportion of non chickenwing LAA type, and a tendency for eccentric, oval-shaped LAA ostia; however, there were no other differences seen with regards to LAA volume or depth. Indexed values for LA, PV and LAA anatomy corrected for body size were broadly similar. CONCLUSIONS: In a cohort of individuals matched for AF risk factors, we could find no strong evidence of ethnic differences in LA, PV, and LAA characteristics that may explain a predisposition of Indigenous Australians for atrial arrhythmogenesis. These findings, in conjunction with our previous data showing highly prevalent cardiometabolic risk factors in Indigenous Australians with AF, suggest that it is these conditions that are more likely responsible for the AF substrate in these individuals. Continued efforts should therefore be directed towards risk factor management in an attempt to prevent and minimise the effects of AF in Indigenous Australians.

Radial-to-femoral pressure gradient quantification in cardiac surgery.

Background: A radial-to-femoral pressure gradient (RFPG) can occur in roughly one-third of cardiac surgical patients. Such a gradient has been associated with smaller stature and potentially smaller radial artery diameter. We hypothesized that preoperative radial artery diameter could be a predictor of RFPG. We also investigated the clinical impact of using a femoral versus a radial arterial catheter in terms of vasoactive support. Methods: Using ultrasound, we measured the bilateral radial artery diameters of 160 cardiac surgical patients. All arterial pressure values were continuously recorded. Significant RFPG was defined as ≥25 mm Hg in systolic and/or ≥10 mm Hg in mean arterial pressure. One hundred and forty-nine additional patients were used to validate the impact of our observations. Results: Using 78,013 pressure datapoints in 129 patients, 34.8% of patients had an RFPG with a mean duration of 54 ± 48 minutes. Patients with a radial artery diameter <1.8 mm were more likely to have an RFPG (n = 14 [48.3%] vs 12 [22.2%]; P = .042). Patients with only a radial catheter received more phenylephrine (P = .016) despite undergoing shorter and less complex procedures. In the validation cohort, similar observations were made, and patients with a radial artery catheter received a longer duration of vasoactive support in the intensive care unit. Conclusions: A significant RFPG occurs in one-third of cardiac surgical patients and in 48% of those with a radial artery diameter <1.8 mm. The use of a single radial arterial catheter instead of dual radial and femoral catheters was associated with greater vasopressor requirements in the operating room and in the intensive care unit. We do not recommend the use of a single radial artery catheter in cardiac surgery.

Standardised computed tomographic assessment of left atrial morphology and tissue thickness in humans.

AIMS: Left atrial (LA) remodelling is a common feature of many cardiovascular pathologies and is a sensitive marker of adverse cardiovascular outcomes. The aim of this study was to establish normal ranges for LA parameters derived from coronary computed tomographic angiography (CCTA) imaging using a standardised image processing pipeline to establish normal ranges in a previously described cohort. METHODS: CCTA imaging from 193 subjects recruited to the Budapest GLOBAL twin study was analysed. Indexed LA cavity volume (LACVi), LA surface area (LASAi), wall thickness and LA tissue volume (LATVi) were calculated. Wall thickness maps were combined into an atlas. Indexed LA parameters were compared with clinical variables to identify early markers of pathological remodelling. RESULTS: LACVi is similar between sexes (31 ml/m2 v 30 ml/m2) and increased in hypertension (33 ml/m2 v 29 ml/m2, p = 0.009). LASAi is greater in females than males (47.8 ml/m2 v 45.8 ml/m2 male, p = 0.031). Median LAWT was 1.45 mm. LAWT was lowest at the inferior portion of the posterior LA wall (1.14 mm) and greatest in the septum (median = 2.0 mm) (p < 0.001). Conditions known to predispose to the development of AF were not associated with differences in tissue thickness. CONCLUSIONS: The reported LACVi, LASAi, LATVi and tissue thickness derived from CCTA may serve as reference values for this age group and clinical characteristics for future studies. Increased LASAi in females in the absence of differences in LACVi or LATVi may indicate differential LA shape changes between the sexes. AF predisposing conditions, other than sex, were not associated with detectable changes in LAWT.Clinical trial registration:http://www.ClinicalTrials.gov/NCT01738828.

Psoriasis Severity, Comorbidities, and Treatment Response Differ among Geographic Regions in the United States.

Little is known about how psoriatic disease characteristics and treatment outcomes differ geographically in the United States. Our aim was to explore real-world, geographic variations in the use of biologic classes and outcomes within the Corrona Psoriasis Registry. Patient demographics and disease characteristics were assessed at biologic initiation and at 6 months. Logistic regressions were conducted to evaluate the odds of achieving targeted outcomes for seven United States geographic regions. We examined 737 biologic initiations among 717 patients. IL-17 inhibitors were used most frequently (45%), followed by IL-12‒IL-23 and IL-23 inhibitors (38%) and TNF inhibitors (17%). The proportions of patients with obesity (body mass index > 30) and very severe psoriasis (body surface area > 20) were greatest in the East South Central and West South Central regions. After adjusting for age, sex, race, body mass index, and baseline body surface area, decreased odds of achieving 75% improvement in PASI at 6 months were observed among patients in the East South Central (OR = 0.47, 95% confidence interval = 0.28-0.79, P = 0.004), West South Central (OR = 0.43, 95% confidence interval = 0.22-0.87, P = 0.019), and Pacific (OR = 0.49, 95% confidence interval = 0.28-0.84, P = 0.010) regions compared with those observed among patients in the Northeast. The East South Central and West South Central regions may have the greatest frequencies of very severe disease burden and, along with the Pacific region, may be less likely to achieve targeted response within 6 months of initiating biologic therapy.

Transcatheter Aortic Valve Replacement in Asia: Present Status and Future Perspectives.

Over the last decade, based on evidence from multiple randomized clinical trials, transcatheter aortic valve replacement (TAVR) has become the established treatment for patients with symptomatic severe aortic stenosis. Despite the overwhelming expansion of TAVR in Western countries, the initial uptake and widespread adoption of this procedure have been relatively delayed in Asian countries, owing to the high cost of devices; limited local health and reimbursement policies; and lack of specific training/proctoring program, specialized heart team, or dedicated infrastructure. Furthermore, it has not yet been determined whether there are substantial interracial and ethnic differences in the clinical characteristics, comorbidities, and anatomic features, as well as procedural and long-term outcomes, in patients receiving TAVR. In this review, we provide not only a comprehensive look at the current status and outcomes of TAVR in Asian populations compared with those of Western populations but also a perspective on the future of TAVR in Asia.