| 1. |
- Bergfeldt, Lennart, 1950, et al.
(författare)
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Spatial peak and mean QRS-T angles: A comparison of similar but different emerging risk factors for cardiac death.
- 2020
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Ingår i: Journal of electrocardiology. - : Elsevier BV. - 1532-8430 .- 0022-0736. ; 61, s. 112-120
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Tidskriftsartikel (refereegranskat)abstract
- The spatial peak and mean QRS-T angles are scientifically but not clinically established risk factors for cardiovascular events including cardiac death. The study aims were to compare these angles, assess their association with hypertension (HT) and diabetes mellitus (DM), and explore the relation between the mean QRS-T angle and the ventricular gradient (VG; reflecting electrical heterogeneity), which both are derived from the QRSarea and Tarea vectors.Altogether 1094 participants (aged 50-65years, 550 women) from the pilot of the population-based Swedish CArdioPulmonary bioImage Study with Frank vectorcardiographic recordings were included and divided into 5 subgroups: apparently healthy n=320; HT n=311; DM n=33; DM+HT n=53; miscellaneous conditions n=377. Abnormal peak and mean QRS-T angles were defined as >95th percentile.Peak QRS-T angles were generally narrower than the mean QRS-T angles; both were narrower in women than in men. Abnormal peak (>124°) and/or mean (>119°) QRS-T angles were found in 73 participants (6.7%). The concordance regarding abnormal versus normal-borderline QRS-T angles was good (Cohen's kappa 0.61). The prevalence of abnormal angles varied from 2.5% in healthy to 21.2% in DM. There was an inverse logarithmical relation between the mean QRS-T angle and the VG.The peak and mean QRS-T angles are not interchangeable but complementary. DM, HT, sex and absence of disease are important determinants of both QRS-T angles. The mean QRS-T angle and the VG relationship is complex. All three VCG derived measures reflect related but differing electrophysiological properties and have potential prognostic value vis-à-vis cardiovascular events.
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| 2. |
- Bergfeldt, Lennart, 1950, et al.
(författare)
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Ventricular repolarization duration and dispersion adaptation after atropine induced rapid heart rate increase in healthy adults.
- 2017
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Ingår i: Journal of electrocardiology. - : Elsevier BV. - 1532-8430 .- 0022-0736. ; 50:4, s. 424-432
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Tidskriftsartikel (refereegranskat)abstract
- Proper adaptation of ventricular repolarization (VR) to rapid heart rate (HR) increase is crucial for cardiac electro-mechanical function. The pattern and temporal aspects of this adaptation and its components (duration and dispersion) during normal conduction are, however, incompletely known in humans and were the topic of this study.The VR duration (QT & QTpeak) and dispersion (Tamplitude, Tarea & ventricular gradient; VG) responses were studied by continuous vectorcardiogram after a bolus injection of atropine 0.04mg/kg b.w. in 31 healthy young adults (16 men). The primary measure (T90 End) was the time to reach 90% change from baseline to end value 300s later. Mean (SD) of T90 End was 23 (9) s for a 41% RR decrease, 130 (35) s for a 16% QTend decrease and 110 (36) s for a 19% QTpeak decrease; the response was single-exponential for these measures. For 35-43% decreases of Tamplitude, Tarea & VG, mean (SD) of T90 End were 21 (10), 38 (20) and 40 (23) s and the response pattern was double-exponential with varying overshoot.VR duration and dispersion responses to a very rapid HR increase during normal conduction differed substantially. In contrast to the well-known single-exponential delay in VR duration adaptation the responses of VR dispersion measures were double-exponential and much more rapid. We describe a new and completely non-invasive phenotypic characterization of different components of VR adaptation.
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| 3. |
- Lorant, Camilla, et al.
(författare)
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Risk Factors for Developing BK Virus-Associated Nephropathy : A Single-Center Retrospective Cohort Study of Kidney Transplant Recipients
- 2022
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Ingår i: Annals of Transplantation. - 1425-9524 .- 2329-0358. ; 27
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND BK virus (BKV) infection after kidney transplantation leads to BKV-associated nephropathy (BKVAN) in up to 10% of recipients, and is associated with an increased risk of allograft dysfunction or loss. The objective of this study was to estimate the incidence of BKVAN and to analyze whether enhanced induction is associated with an increased risk of BKVAN, possibly justifying more intensive surveillance.MATERIAL AND METHODS This was a single-center retrospective cohort study. All patients who underwent kidney transplantation or simultaneous pancreas and kidney transplantation at the Uppsala University Hospital in Sweden between 2005 and 2014 were included, a period when BKV screening was not yet implemented. The effect of enhanced induction, defined as treatment with thymoglobulin, rituximab, and/or eculizumab, often in combination with IVIg and glycosorb, immunoadsorption and/or plasmapheresis/apheresis, was analyzed in a multivariable Cox proportional hazards model together with sex, age, cytomegalovirus mismatch (donor+/recipient-) and rejection treatment as co-predictors. Further, the effects of BKVAN on graft survival was analyzed in a univariable Cox proportional hazards model.RESULTS In total 44 of 928 (4.7%) patients developed a biopsy-verified BKVAN 4.8 (1.5-34.2) months after transplantation. Male sex was identified as a risk factor (HR 2.02, P=0.04) but not enhanced induction. Patients with BKVAN experienced a significantly higher risk of graft loss (HR 4.37, P<0.001).CONCLUSIONS Male sex, but not enhanced induction, was found to be a risk factor for BKVAN development after kidney transplantation. BKVAN is associated with an increased risk of graft loss.
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| 4. |
- Lorant, Camilla, et al.
(författare)
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The risk factors associated with post-transplantation BKPyV nephropathy and BKPyV DNAemia : a prospective study in kidney transplant recipients
- 2024
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Ingår i: BMC Infectious Diseases. - : BioMed Central (BMC). - 1471-2334. ; 24
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Tidskriftsartikel (refereegranskat)abstract
- Background: BK polyomavirus (BKPyV) infection after kidney transplantation can lead to serious complications such as BKPyV-associated nephropathy (BKPyVAN) and graft loss. The aim of this study was to investigate the incidence of BKPyVAN after implementing a BKPyV screening program, to map the distribution of BKPyV genotypes and subtypes in the Uppsala-orebro region and to identify host and viral risk factors for clinically significant events.Methods This single-center prospective cohort study included kidney transplant patients aged >= 18 years at the Uppsala University Hospital in Sweden between 2016 and 2018. BKPyV DNA was analyzed in plasma and urine every 3 months until 18 months after transplantation. Also genotype and subtype were determined. A logistic regression model was used to analyze selected risk factors including recipient sex and age, AB0 incompatibility and rejection treatment prior to BKPyVAN or high-level BKPyV DNAemia.Results: In total, 205 patients were included. Of these, 151 (73.7%) followed the screening protocol with 6 plasma samples, while184 (89.8%) were sampled at least 5 times. Ten (4.9%) patients developed biopsy confirmed BKPyVAN and 33 (16.1%) patients met criteria for high-level BKPyV DNAemia. Male sex (OR 2.85, p = 0.025) and age (OR 1.03 per year, p = 0.020) were identified as significant risk factors for developing BKPyVAN or high-level BKPyV DNAemia. BKPyVAN was associated with increased viral load at 3 months post transplantation (82,000 vs. < 400 copies/mL; p = 0.0029) and with transient, high-level DNAemia (n = 7 (27%); p < 0.0001). The most common genotypes were subtype Ib2 (n = 50 (65.8%)) and IVc2 (n = 20 (26.3%)).Conclusions: Male sex and increasing age are related to an increased risk of BKPyVAN or high-level BKPyV DNAemia. BKPyVAN is associated with transient, high-level DNAemia but no differences related to viral genotype were detected.
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| 5. |
- Lundahl, Gunilla, et al.
(författare)
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Automatic identification of a stable QRST complex for non-invasive evaluation of human cardiac electrophysiology.
- 2020
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 15:9
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Tidskriftsartikel (refereegranskat)abstract
- A vectorcardiography approach to electrocardiology contributes to the non-invasive assessment of electrical heterogeneity in the ventricles of the heart and to risk stratification for cardiac events including sudden cardiac death. The aim of this study was to develop an automatic method that identifies a representative QRST complex (QRSonset to Tend) from a Frank vectorcardiogram (VCG). This method should provide reliable measurements of morphological VCG parameters and signal when such measurements required manual scrutiny.Frank VCG was recorded in a population-based sample of 1094 participants (550 women) 50-65 years old as part of the Swedish CArdioPulmonary bioImage Study (SCAPIS) pilot. Standardized supine rest allowing heart rate stabilization and adaptation of ventricular repolarization preceded a recording period lasting ≥5 minutes. In the Frank VCG a recording segment during steady-state conditions and with good signal quality was selected based on QRST variability. In this segment a representative signal-averaged QRST complex from cardiac cycles during 10s was selected. Twenty-eight morphological parameters were calculated including both conventional conduction intervals and VCG-derived parameters. The reliability and reproducibility of these parameters were evaluated when using completely automatic and automatic but manually edited annotation points.In 1080 participants (98.7%) our automatic method reliably selected a representative QRST complex where its instability measure effectively identified signal variability due to both external disturbances ("noise") and physiologic and pathophysiologic variability, such as e.g. sinus arrhythmia and atrial fibrillation. There were significant sex-related differences in 24 of 28 VCG parameters. Some VCG parameters were insensitive to the instability value, while others were moderately sensitive.We developed an automatic process for identification of a signal-averaged QRST complex suitable for morphologic measurements which worked reliably in 99% of participants. This process is applicable for all non-invasive analyses of cardiac electrophysiology including risk stratification for cardiac death based on such measurements.
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| 6. |
- Pretolani, Marina, et al.
(författare)
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Effectiveness of bronchial thermoplasty in patients with severe refractory asthma : Clinical and histopathologic correlations
- 2017
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749. ; 139:4, s. 1176-1185
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Tidskriftsartikel (refereegranskat)abstract
- Background: The effectiveness of bronchial thermoplasty (BT) has been reported in patients with severe asthma, yet its effect on different bronchial structures remains unknown. Objective: We sought to examine the effect of BT on bronchial structures and to explore the association with clinical outcome in patients with severe refractory asthma. Methods: Bronchial biopsy specimens (n = 300) were collected from 15 patients with severe uncontrolled asthma before and 3 months after BT. Immunostained sections were assessed for airway smooth muscle (ASM) area, subepithelial basement membrane thickness, nerve fibers, and epithelial neuroendocrine cells. Histopathologic findings were correlated with clinical parameters. Results: BT significantly improved asthma control and quality of life at both 3 and 12 months and decreased the numbers of severe exacerbations and the dose of oral corticosteroids. At 3 months, this clinical benefit was accompanied by a reduction in ASM area (median values before and after BT, respectively: 19.7% [25th-75th interquartile range (IQR), 15.9% to 22.4%] and 5.3% [25th-75th IQR], 3.5% to 10.1%, P < .001), subepithelial basement membrane thickening (4.4 μm [25th-75th IQR, 4.0-4.7 μm] and 3.9 μm [25th-75th IQR, 3.7-4.6 μm], P = 0.02), submucosal nerves (1.0 ‰ [25th-75th IQR, 0.7-1.3 ‰] immunoreactivity and 0.3 ‰ [25th-75th IQR, 0.1-0.5 ‰] immunoreactivity, P < .001), ASM-associated nerves (452.6 [25th-75th IQR, 196.0-811.2] immunoreactive pixels per mm2 and 62.7 [25th-75th IQR, 0.0-230.3] immunoreactive pixels per mm2, P = .02), and epithelial neuroendocrine cells (4.9/mm2 [25th-75th IQR, 0-16.4/mm2] and 0.0/mm2 [25th-75th IQR, 0-0/mm2], P = .02). Histopathologic parameters were associated based on Asthma Control Test scores, numbers of exacerbations, and visits to the emergency department (all P ≤ .02) 3 and 12 months after BT. Conclusion: BT is a treatment option in patients with severe therapy-refractory asthma that downregulates selectively structural abnormalities involved in airway narrowing and bronchial reactivity, particularly ASM, neuroendocrine epithelial cells, and bronchial nerve endings.
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| 7. |
- Rao, Shuan, et al.
(författare)
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RANK rewires energy homeostasis in lung cancer cells and drives primary lung cancer
- 2017
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Ingår i: Genes & Development. - : Cold Spring Harbor Laboratory. - 0890-9369 .- 1549-5477. ; 31:20, s. 2099-2112
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Tidskriftsartikel (refereegranskat)abstract
- Lung cancer is the leading cause of cancer deaths. Besides smoking, epidemiological studies have linked female sex hormones to lung cancer in women; however, the underlying mechanisms remain unclear. Here we report that the receptor activator of nuclear factor-kB (RANK), the key regulator of osteoclastogenesis, is frequently expressed in primary lung tumors, an active RANK pathway correlates with decreased survival, and pharmacologic RANK inhibition reduces tumor growth in patient-derived lung cancer xenografts. Clonal genetic inactivation of KRas(G12D) in mouse lung epithelial cells markedly impairs the progression of KRas(G12D)-driven lung cancer, resulting in a significant survival advantage. Mechanistically, RANK rewires energy homeostasis in human and murine lung cancer cells and promotes expansion of lung cancer stem-like cells, which is blocked by inhibiting mitochondrial respiration. Our data also indicate survival differences in KRas(G12D)-driven lung cancer between male and female mice, and we show that female sex hormones can promote lung cancer progression via the RANK pathway. These data uncover a direct role for RANK in lung cancer and may explain why female sex hormones accelerate lung cancer development. Inhibition of RANK using the approved drug denosumab may be a therapeutic drug candidate for primary lung cancer.
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| 8. |
- Vahedi, Farzad, et al.
(författare)
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Instability of repolarization in LQTS mutation carriers compared to healthy control subjects assessed by vectorcardiography
- 2013
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Ingår i: Heart Rhythm. - : Elsevier BV. - 1547-5271 .- 1556-3871. ; 10:8, s. 1169-1175
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Potassium channel dysfunction in congenital and acquired forms of long QT syndrome types 1 and 2 (LQT1 and LQT2) increases the beat-to-beat variability of the (IT interval. OBJECTIVE To study about the little known variability (instability) of other aspects of ventricular repolarization (VR) in humans by using vectorcardiography. METHODS Beat-to-beat analysis was performed regarding vectorcardiography derived RR, QRS, and QT intervals, as well as T vector- and T vector loop-based parameters during 1-minute recordings of uninterrupted sinus rhythm at rest in 41 adult LQT1 (n = 31) and LQT2 (n = 10) mutation carriers and 41 age- and sex-matched control subjects. The short-term variability for each parameter, describing the mean orthogonal distance to the line of identity on the Poincare plot, was calculated. RESULTS Mutation carriers showed significantly larger (by a factor 2) instability in most VR parameters compared to controls despite higher instantaneous heart rate variability (STVRR) in the control group. The longer the (IT interval, the greater was its instability, and the instability of VR dispersion measures. CONCLUSIONS A greater instability of most aspects of VR already at rest seems to be a salient feature in both LQT1 and LQT2, which might pave the way for early afterdepolarizations and torsades de pointes ventricular tachycardia. In contrast, no signs of increased VR dispersion per se were observed in mutation carriers.
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