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With the widespread use of integrase inhibitors and the expanding use of long-acting cabotegravir in both pre-exposure prophylaxis and antiretroviral treatment, molecular surveillance on the transmission of integrase resistance has regained clinical significance. This study aimed to determine the frequency of INSTI-transmitted drug resistance mutations (DRMs) among treatment-naïve individuals in Poland from 2016 to 2023. INSTI resistance was analyzed in 882 antiretroviral treatment-naïve individuals using Sanger sequencing. Integrase DRMs were defined based on the Stanford HIV drug resistance database scores. Phylogeny was used to investigate subtyping and clustering. For the analysis of time-trends, logistic regression was used. Major (E138K and R263K) integrase mutations were detected in 0.45% of cases with minor resistance observed in 14.85%, most commonly (13.95%) E157Q. Overall, no major clusters of transmitted drug resistance were identified, and the transmission of E157Q showed a decreasing trend (p < 0.001). While the frequency of sub-subtype A6 increased, it was predominantly found among migrants and associated with L74 mutations. The frequency of major integrase-transmitted DRMs remains low, despite the changes in subtype variability. Surveillance of changing HIV molecular variation patterns is vital from the perspective of the optimal use of integrase inhibitors, especially due to expanding long-acting cabotegravir implementation.

Abstract Background Adults with congenital heart disease (ACHD) are a group with an increased risk of thromboembolic complications and arrhythmias. Vitamin K antagonists are the most commonly used thromboprophylaxis therapy in this population. Studies on the efficacy and safety of novel oral anticoagulants (NOAC) are scare in ACHD. A retrospective study on ACHD patients on NOAC treatment registered in the National Quality Registry for Congenital Heart Disease, SWEDCON, and National Quality Registry for Atrial fibrillation and Anticoagulation, AuriculA, from Southern Sweden. Results Thirty patients who had been taking NOAC treatment for a minimum of 3 months were included. Their median age was 55 years (SD 17 years) and 57% were male. Median follow-up was 17 months (IQR: 10–41). Eliquis was the most used NOAC (47%). Median CHA2DS2-VASc score was 2 (IQR: 0–3) and HAS-BLED was 1 (IQR: 0–2). Complex ACHD was prevalent in 27% of the patients. No thromboembolic events were recorded; however, one major bleeding, unspecified, was reported during the total cumulative patient follow-up time of 64 years. Conclusions The results of our study, although limited in size, suggest that NOAC appear safe and effective in ACHD patients. Further and larger studies on NOAC in ACHD patients are warranted.

With the widespread use of integrase inhibitors and the expanding use of long-acting cabotegravir in both pre-exposure prophylaxis and antiretroviral treatment, molecular surveillance on the transmission of integrase resistance has regained clinical significance. This study aimed to determine the frequency of INSTI-transmitted drug resistance mutations (DRMs) among treatment-naïve individuals in Poland from 2016 to 2023. INSTI resistance was analyzed in 882 antiretroviral treatment-naïve individuals using Sanger sequencing. Integrase DRMs were defined based on the Stanford HIV drug resistance database scores. Phylogeny was used to investigate subtyping and clustering. For the analysis of time-trends, logistic regression was used. Major (E138K and R263K) integrase mutations were detected in 0.45% of cases with minor resistance observed in 14.85%, most commonly (13.95%) E157Q. Overall, no major clusters of transmitted drug resistance were identified, and the transmission of E157Q showed a decreasing trend (p < 0.001). While the frequency of sub-subtype A6 increased, it was predominantly found among migrants and associated with L74 mutations. The frequency of major integrase-transmitted DRMs remains low, despite the changes in subtype variability. Surveillance of changing HIV molecular variation patterns is vital from the perspective of the optimal use of integrase inhibitors, especially due to expanding long-acting cabotegravir implementation. [ABSTRACT FROM AUTHOR]

BackgroundDuring pregnancy and delivery, hemodynamics are altered and complex congenital heart disease has been associated with adverse maternal and neonatal outcomes. We sought to investigate pregnancy outcome and complications in relation to complexity of heart condition.Materials and methodsWe studied women with ACHD discussed at multidisciplinary conferences at Lund University Hospital March 2009-May 2021. We studied 149 pregnancies in 101 women. We scored each woman retrospectively according to the modified World Health Organization (mWHO) risk classification and included patients in risk class I (n = 36, 24.1%), II (n = 43, 28.9%), II-III (n = 43, 28.9%), III (n = 24, 16.1%) and IV (n = 3, 2.0%).ResultsWomen with mWHO class ≥III underwent cesarean section more often than women in less complex mWHO classes, (OR, 5.1; 95% CI, 2.0-12.5; p1000 ml or cardiac defect in the neonate depending on WHO-class. Women in mWHO classes III-IV had a higher rate of fetal growth restriction (FGR) compared to women in mWHO classes I, II, II-III (pConclusionsOur findings indicate that women with more complex heart disease (mWHO classes III or IV) tend to have a higher rate of cesarean section, premature birth and FGR.

Background: The risk of adults with a congenital heart defect (ACHD) developing heart failure, stroke, arrhythmias, and the need for valve replacement is increased compared to healthy peers. Evidence for the use of novel oral anticoagulants (NOAC) in this patient group is still lacking and vitamin K antagonists (VKA) are the primary choice for patients with a mechanical valve. The present aim was to determine the rate of thromboembolic and major bleeding events in ACHD patients on VKA therapy. Methods: This was a retrospective study on ACHD patients on VKA treatment registered in the National Quality Registry for Congenital Heart Disease, SWEDCON, and Atrial fibrillation and Anticoagulation, AuriculA, from Southern Sweden. Results: 213 patients were included with a mean age of 50 years (±18) years and a mean follow-up of 6.6 years (±3.3 years), 16% had complex defects and 41% had valvular VKA therapy indication. In total, 34 complications were registered, of which 14 were thromboembolic events and 20 were major bleeding events. The rate of thromboembolism and major bleeding events was 1.0 (95% CI: 0.6–1.6) and 1.4 (95% CI: 0.9–2.2) per 100 patient-years, respectively. Forty-three patients died during the study period. The mortality rate was 3.1 per 100 patient-years (95% CI: 2.2–4.1). Conclusion: We found a low rate of thromboembolic events and major bleeding events for low-moderate risk ACHD patients with good quality of VKA anticoagulation. The target of TTR>65% for ACHD patients is recommended.

Abstract The occurrence of HIV-1 subtypes differs worldwide and within Europe, with non-B variants mainly found across different exposure groups. In this study, we investigated the distribution and temporal trends in HIV-1 subtype variability across Poland between 2015 and 2019. Sequences of the pol gene fragment from 2518 individuals were used for the analysis of subtype prevalence. Subtype B was dominant (n = 2163, 85.90%). The proportion of subtype B-infected individuals decreased significantly, from 89.3% in 2015 to 80.3% in 2019. This was related to the increasing number of subtype A infections. In 355 (14.10%) sequences, non-B variants were identified. In 65 (2.58%) samples, recombinant forms (RFs) were noted. Unique recombinant forms (URFs) were found in 30 (1.19%) sequences. Three A/B recombinant clusters were identified of which two were A6/B mosaic viruses not previously described. Non-B clades were significantly more common among females (n = 81, 22.8%, p = 0.001) and heterosexually infected individuals (n = 45, 32.4%, p = 0.0031). The predominance of subtype B is evident, but the variability of HIV-1 in Poland is notable. Almost half of RFs (n = 65, 2.58%) was comprised of URFs (n = 30, 1.19%); thus those forms were common in the analyzed population. Hence, molecular surveillance of identified variants ensures recognition of HIV-1 evolution in Poland.

Background Little is known about the cause of death (CoD) in patients with transposition of the great arteries palliated with a Mustard or Senning procedure. The aim was to describe the CoD for patients with the Mustard and Senning procedure during short‐ (20 years) follow‐up after the operation. Methods and Results This is a retrospective, descriptive multicenter cohort study including all Nordic patients (Denmark, Finland, Norway, and Sweden) who underwent a Mustard or Senning procedure between 1967 and 2003. Patients who died within 30 days after the index operation were excluded. Among 968 patients with Mustard/Senning palliated transposition of the great arteries, 814 patients were eligible for the study, with a mean follow‐up of 33.6 years. The estimated risk of all‐cause mortality reached 36.0% after 43 years of follow‐up, and the risk of death was highest among male patients as compared with female patients (P=0.004). The most common CoD was sudden cardiac death (SCD), followed by heart failure/heart transplantation accounting for 29% and 27%, respectively. During short‐, mid‐, and long‐term follow‐up, there was a change in CoD with SCD accounting for 23.7%, 46.6%, and 19.0% (P=0.002) and heart failure/heart transplantation 18.6%, 22.4%, and 46.6% (P=0.0005), respectively. Conclusions Among patients corrected with Mustard or Senning transposition of the great arteries, the most common CoD is SCD followed by heart failure/heart transplantation. The CoD changes as the patients age, with SCD as the most common cause in adolescence and heart failure as the dominant cause in adulthood. Furthermore, the risk of all‐cause mortality, SCD, and death attributable to heart failure or heart transplantation was increased in men >10 years after the Mustard/Senning operation.

Background: Marfan Syndrome (MFS) has been associated with increased aortic stiffness and left ventricular dysfunction. The latter may be due to the underlying genotype and/or secondary to aortic stiffening (vascular-ventricular interaction). The aim of this study was to characterize arterial and cardiac function in MFS using a multimodal approach.Methods: Prospective observational study of MFS patients and healthy controls. Methods included echocardiography, ascending aortic distensibility, common carotid intima media thickness [cIMT], parameters of wave reflection, carotid-femoral pulse wave velocity [cfPWV]), reactive hyperemia index [RHI], and biomarker analysis (Olink, CVII panel).Results: We included 20 patients with MFS and 67 controls. Ascending aortic distensibility, cIMT and RHI were decreased, while all parameters of arterial wave reflection, stiffness and BNP levels were increased in the MFS group. Both systolic and diastolic function were impaired relative to controls. Within the MFS group, no significant correlation between arterial and cardiac function was identified. However, cfPWV correlated significantly with indexed left ventricular mass and volume in MFS. Bran natriuretic peptide (BNP) was the only biomarker significantly elevated in MFS following correction for age and sex.Conclusions: MFS patients have generally increased aortic stiffness, endothelial dysfunction and BNP levels while cIMT is decreased, supporting that the mechanism of general stiffening is different from acquired vascular disease. CfPWV is associated with cardiac size, blood pressure and BNP in MFS patients. These may be early markers of disease progression that are suitable for monitoring pharmacological treatment effects in MFS patients.

Abstract Background One of the most serious secondary manifestations of Cardiovascular Disease (CVD) is coronary atherosclerosis. This study aimed to evaluate whether aged garlic extract (AGE) can influence coronary artery calcification (CAC) and to predict the individual effect of AGE using a standard process for data mining (CRISP–DM). Method This was a single-center parallel randomized controlled study in a university hospital in Europe. Patients were randomized, in a double-blind manner, through a computer-generated randomization chart. Patients with a Framingham risk score ≥ 10 after CT scan (n = 104) were randomized to an intake of placebo or AGE (2400 mg daily) for 1 year. Main outcome measures were changes in CAC score and secondary outcome measures changes in blood pressure, fasting blood glucose, blood lipids and inflammatory biomarkers. Result 104 patients were randomized and 46 in the active group and 47 in the placebo group were analyzed. There was a significant (p

Abstract Background The aim of this retrospective study was to evaluate the relationship between right ventricular function derived from cardiac magnetic resonance imaging (CMR), echocardiography and exercise stress test performance, NT-proBNP (N-terminal proB-type natriuretic peptide) level and NYHA class in patients with a systemic right ventricle. Methods All patients with congenitally corrected transposition of the great arteries (ccTGA), or transposition of the great arteries after Mustard or Senning procedures, (TGA) followed at our centre who had undergone CMR, echocardiography, an exercise stress test and blood sampling, were included in the study. Results We examined 11 patients (six after the Senning procedure, one after the Mustard procedure, and four ccTGA) who have a median age of 32 years (22-67 years). A significant correlation was observed between the systemic ventricular function, expressed as the CMR-derived right ventricular ejection fraction and the right ventricular global longitudinal strain (r= -0.627; p=0.039). Conclusion We have demonstrated that in patients with ccTGA or TGA right ventricular global longitudinal strain may be useful in the evaluation of the systemic right ventricular function.

Background: Peripheral muscle factors are presumed to be contributors to the reduced exercise capacity in congenital heart disease (CHD), but the underlying mechanisms are poorly understood. The aim was to investigate if muscle oxygenation, at rest and during exercise, and the resting blood flow in the calf muscle is impaired in adults with complex CHD in comparison to controls. Method: Seventy-four adults with complex CHD (35.6 ± 14.3 years, females n = 22 [30%], males n = 52 [70%]) and seventy-four age and sex matched subjects were recruited. Muscle oxygenation was successfully determined using near-infrared spectroscopy on the medial portion of m. gastrocnemius in 63 patients and 67 controls. Measurements were made at rest, during venous occlusion to estimate blood flow (indicated by slope increase of total haemoglobin, HbT), and post arterial occlusion. Additionally, measurements were made at the onset of isotonic unilateral heel-lifts to exhaustion and during recovery post exercise. Results: Adults with CHD had a slower desaturation rate at exercise onset (−7.7 ± 4.3%StO2x3.5sec−1 vs. −11.7 ± 5.8%StO2x3.5sec−1, p

Abstract Objective To evaluates the effect of food intake on 92 oncological biomarkers to evaluate whether the timing of blood sampling could be relevant. Twenty-two healthy subjects were investigated. A total of 92 biomarkers were measured before a standardised meal as well as 30 and 120 min afterwards with the Proseek Multiplex Oncology II kit. Results The levels of 6 biomarkers decreased significantly (P

Background: Bicuspid aortic valve (BAV), the most common congenital cardiac anomaly, has been associated with an aortopathy, increased aortic stiffness and diastolic dysfunction. The involved mechanisms and impact of age remain unclear. It was the aim of this study to characterize arterial and cardiac function, their correlation, and the effect of age in children and adults with a history of BAV.Methods: Multimodal cardiovascular assessment included echocardiography, ascending aortic distensibility, common carotid intima media thickness [cIMT], parameters of wave reflection [central (cAIx75) and peripheral (pAIx75) augmentation index corrected to a heart rate of 75/min, aging index (AI)], carotid-femoral pulse wave velocity [cfPWV], and endothelial function (EndoPAT). Multivariable linear regression and correlation analyses were performed.Results: We included 47 BAV patients and 84 controls (age 8–65 years). Ascending aortic stiffness, pulse wave reflection (cAIx75, pAIx75, and AI) and central blood pressure were significantly increased in patients with BAV. However, PWV, cIMT, and endothelial function were not significantly different from controls. BAV patients had marginally reduced diastolic (E': β = −1.5, p < 0.001) but not systolic function compared to controls. Overall, all parameters of arterial stiffness had moderate-strong correlations with diastolic dysfunction and age. In the BAV group, ascending aortic distensibility had the strongest correlation with diastolic dysfunction.Conclusions: BAV is associated with increased proximal arterial stiffness and wave reflection. However, PWV and cIMT are not increased, and endothelial function is preserved. This suggests that the mechanism of arterial and cardiac stiffening is different from patients with acquired heart diseases.

Abstract Background The maintenance of considerable genetic variation in sexually selected traits (SSTs) is puzzling given directional selection expected to act on these traits. A possible explanation is the existence of a genotype-by-environment (GxE) interaction for fitness, by which elaborate SSTs are favored in some environments but selected against in others. In the current study, we look for such interactions for fitness-related traits in the bulb mite, a male-dimorphic species with discontinuous expression of a heritable SST in the form of enlarged legs that are used as weapons. Results We show that evolution at 18 °C resulted in populations with a higher prevalence of this SST compared to evolution at 24 °C. We further demonstrate that temperature modified male reproductive success in a way that was consistent with these changes. There was a genotype-by-environment interaction for reproductive success – at 18 °C the relative reproductive success of armored males competing with unarmored ones was higher than at the moderate temperature of 24 °C. However, male morph did not have interactive effects with temperature with respect to other life history traits (development time and longevity). Conclusions A male genotype that is associated with the expression of a SST interacted with temperature in determining male reproductive success. This interaction caused an elaborate SST to evolve in different directions (more or less prevalent) depending on the thermal environment. The implication of this finding is that seasonal temperature fluctuations have the potential to maintain male polymorphism within populations. Furthermore, spatial heterogeneity in thermal conditions may cause differences among populations in SST selection. This could potentially cause selection against male immigrants from populations in different environments and thus strengthen barriers to gene flow.

Abstract Background Myocardial performance index (MPI) has been investigated in a variety of populations, but the effect of food intake has not been evaluated. We assessed whether myocardial performance index is affected by food intake in healthy subjects. Methods Twenty-three healthy subjects aged 25.6 ± 4.5 years were investigated. MPI was measured before, 30 min after, and 110 min after a standardized meal. Results MPI decreased significantly (P