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Introduction: Imatinib has led to a phenomenal progress in the treatment of GIST. A rare and lesser-known side effect of imatinib is pneumonitis, an uncommon multicausal interstitial lung disease. Methods: Patients registered within the Dutch GIST Registry (DGR) were reviewed. For the patients identified with an imatinib-induced pneumonitis we reported the time on imatinib to develop pneumonitis, how the pneumonitis was diagnosed, graded and managed, and how the GIST treatment was managed. Cases: Of the 1934 patients registered in the DGR, 1161 patients received imatinib at some point, of which nine patients (0.8 %) were identified with an imatinib-induced pneumonitis. At time of the pneumonitis, patients received a daily imatinib dose of 200–400 mg for a mean duration of 486 days. One patient was able to continue imatinib in a lower dose, in the other eight patients imatinib was interrupted, and six of these patients started prednisolone treatment. After management of the imatinib-induced pneumonitis, four patients stopped imatinib permanently, two patients were rechallenged with imatinib, and two patients started treatment with second-line sunitinib. Conclusion: Imatinib-induced pneumonitis is a rare side effect, which may affect GIST management considerably. After the management of imatinib-induced pneumonitis, clinicians are left with difficult treatment dilemmas.

For deep partial-thickness burns no consensus on the optimal treatment has been reached due to conflicting study outcomes with low quality evidence. Treatment options in high- and middle-income countries include conservative treatment with delayed excision and grafting if needed; and early excision and grafting. The majority of timing of surgery studies focus on survival rather than on quality of life. This study protocol describes a study that aims to compare long-term scar quality, clinical outcomes, and patient-reported outcomes between the treatment options. A multicentre prospective study will be conducted in the three Dutch burn centres (Rotterdam, Beverwijk, and Groningen). All adult patients with acute deep-partial thickness burns, based on healing potential with Laser Doppler Imaging, are eligible for inclusion. During a nine-month baseline period, standard practice will be monitored. This includes conservative treatment with dressings and topical agents, and excision and grafting of residual defects if needed 14-21 days post-burn. The subsequent nine months, early surgery is advocated, involving excision and grafting in the first week to ten days post-burn. The primary outcome compared between the two groups is long-term scar quality assessed by the Patient and Observer Scar Assessment Scale 3.0 twelve months after discharge. Secondary outcomes include clinical outcomes and patient-reported outcomes like quality of life and return to work. The aim of the study is to assess long-term scar quality in deep partial-thickness burns after conservative treatment with delayed excision and grafting if needed, compared to early excision and grafting. Adding to the ongoing debate on the optimal treatment of these burns. The broad range of studied outcomes will be used for the development of a decision aid for deep partial-thickness burns, to fully inform patients at the point of consent to surgery and support optimal person-centred care.

Introduction Current treatment decision-making in high-grade soft-tissue sarcoma (STS) care is not informed by individualised risks for different treatment options and patients’ preferences. Risk prediction tools may provide patients and professionals insight in personalised risks and benefits for different treatment options and thereby potentially increase patients’ knowledge and reduce decisional conflict. The VALUE-PERSARC study aims to assess the (cost-)effectiveness of a personalised risk assessment tool (PERSARC) to increase patients’ knowledge about risks and benefits of treatment options and to reduce decisional conflict in comparison with usual care in high-grade extremity STS patients.Methods The VALUE-PERSARC study is a parallel cluster randomised control trial that aims to include at least 120 primarily diagnosed high-grade extremity STS patients in 6 Dutch hospitals. Eligible patients (≥18 years) are those without a treatment plan and treated with curative intent. Patients with sarcoma subtypes or treatment options not mentioned in PERSARC are unable to participate. Hospitals will be randomised between usual care (control) or care with the use of PERSARC (intervention). In the intervention condition, PERSARC will be used by STS professionals in multidisciplinary tumour boards to guide treatment advice and in patient consultations, where the oncological/orthopaedic surgeon informs the patient about his/her diagnosis and discusses benefits and harms of all relevant treatment options. The primary outcomes are patients’ knowledge about risks and benefits of treatment options and decisional conflict (Decisional Conflict Scale) 1 week after the treatment decision has been made. Secondary outcomes will be evaluated using questionnaires, 1 week and 3, 6 and 12 months after the treatment decision. Data will be analysed following an intention-to-treat approach using a linear mixed model and taking into account clustering of patients within hospitals.Ethics and dissemination The Medical Ethical Committee Leiden-Den Haag-Delft (METC-LDD) approved this protocol (NL76563.058.21). The results of this study will be reported in a peer-review journal.Trial registration number NL9160, NCT05741944.

In recent years genome-wide association studies (GWAS) have uncovered numerous chromosomal loci associated with various electrocardiographic traits and cardiac arrhythmia predisposition. A considerable fraction of these loci lie within inter-genic regions. The underlying trait-associated variants likely reside in regulatory regions and exert their effect by modulating gene expression. Hence, the key to unraveling the molecular mechanisms underlying these cardiac traits is to interrogate variants for association with differential transcript abundance by expression quantitative trait locus (eQTL) analysis. In this study we conducted an eQTL analysis of human heart. For a total of 129 left ventricular samples that were collected from non-diseased human donor hearts, genome-wide transcript abundance and genotyping was determined using microarrays. Each of the 18,402 transcripts and 897,683 SNP genotypes that remained after pre-processing and stringent quality control were tested for eQTL effects. We identified 771 eQTLs, regulating 429 unique transcripts. Overlaying these eQTLs with cardiac GWAS loci identified novel candidates for studies aimed at elucidating the functional and transcriptional impact of these loci. Thus, this work provides for the first time a comprehensive eQTL map of human heart: a powerful and unique resource that enables systems genetics approaches for the study of cardiac traits.

BackgroundVentricular fibrillation (VF) in the setting of acute ST elevation myocardial infarction (STEMI) is a leading cause of mortality. Although the risk of VF has a genetic component, the underlying genetic factors are largely unknown. Since heart rate and ECG intervals of conduction and repolarization during acute STEMI differ between patients who do and patients who do not develop VF, we investigated whether SNPs known to modulate these ECG indices in the general population also impact on the respective ECG indices during STEMI and on the risk of VF.Methods and resultsThe study population consisted of participants of the Arrhythmia Genetics in the NEtherlandS (AGNES) study, which enrols patients with a first STEMI that develop VF (cases) and patients that do not develop VF (controls). SNPs known to impact on RR interval, PR interval, QRS duration or QTc interval in the general population were tested for effects on the respective STEMI ECG indices (stage 1). Only those showing a (suggestive) significant association were tested for association with VF (stage 2). On average, VF cases had a shorter RR and a longer QTc interval compared to non-VF controls. Eight SNPs showed a trend for association with the respective STEMI ECG indices. Of these, three were also suggestively associated with VF.ConclusionsRR interval and ECG indices of conduction and repolarization during acute STEMI differ between patients who develop VF and patients who do not. Although the effects of the SNPs on ECG indices during an acute STEMI seem to be similar in magnitude and direction as those found in the general population, the effects, at least in isolation, are too small to explain the differences in ECGs between cases and controls and to determine risk of VF.

Sudden cardiac death (SCD) continues to be one of the leading causes of mortality worldwide, with an annual incidence estimated at 250,000-300,000 in the United States and with the vast majority occurring in the setting of coronary disease. We performed a genome-wide association meta-analysis in 1,283 SCD cases and >20,000 control individuals of European ancestry from 5 studies, with follow-up genotyping in up to 3,119 SCD cases and 11,146 controls from 11 European ancestry studies, and identify the BAZ2B locus as associated with SCD (P = 1.8×10(-10)). The risk allele, while ancestral, has a frequency of ~1.4%, suggesting strong negative selection and increases risk for SCD by 1.92-fold per allele (95% CI 1.57-2.34). We also tested the role of 49 SNPs previously implicated in modulating electrocardiographic traits (QRS, QT, and RR intervals). Consistent with epidemiological studies showing increased risk of SCD with prolonged QRS/QT intervals, the interval-prolonging alleles are in aggregate associated with increased risk for SCD (P = 0.006).

For deep partial-thickness burns no consensus on the optimal treatment has been reached due to conflicting study outcomes with low quality evidence. Treatment options in high- and middle-income countries include conservative treatment with delayed excision and grafting if needed; and early excision and grafting. The majority of timing of surgery studies focus on survival rather than on quality of life. This study protocol describes a study that aims to compare long-term scar quality, clinical outcomes, and patient-reported outcomes between the treatment options. A multicentre prospective study will be conducted in the three Dutch burn centres (Rotterdam, Beverwijk, and Groningen). All adult patients with acute deep-partial thickness burns, based on healing potential with Laser Doppler Imaging, are eligible for inclusion. During a nine-month baseline period, standard practice will be monitored. This includes conservative treatment with dressings and topical agents, and excision and grafting of residual defects if needed 14–21 days post-burn. The subsequent nine months, early surgery is advocated, involving excision and grafting in the first week to ten days post-burn. The primary outcome compared between the two groups is long-term scar quality assessed by the Patient and Observer Scar Assessment Scale 3.0 twelve months after discharge. Secondary outcomes include clinical outcomes and patient-reported outcomes like quality of life and return to work. The aim of the study is to assess long-term scar quality in deep partial-thickness burns after conservative treatment with delayed excision and grafting if needed, compared to early excision and grafting. Adding to the ongoing debate on the optimal treatment of these burns. The broad range of studied outcomes will be used for the development of a decision aid for deep partial-thickness burns, to fully inform patients at the point of consent to surgery and support optimal person-centred care. [ABSTRACT FROM AUTHOR]