Incidence and risk factors for congestive heart failure in patients with early breast cancer who received anthracycline and/or trastuzumab: a big data analysis of the Korean Health Insurance Review and Assessment service database

Abstract

Purpose

We aimed to analyze the incidence, time to occurrence, and congestive heart failure (CHF) risk factors for early breast cancer patients treated with anthracycline (AC)-based chemotherapy and/or trastuzumab (T) therapy in Korea.

Methods

We included female patients > 19 years old from the Health Insurance Review and Assessment Service database who had no prior CHF history and had been diagnosed with early breast cancer between January 2007 and October 2016.

Results

We included 83,544 patients in our analysis. In terms of crude incidence for CHF, AC followed by T showed the highest incidence (6.3%). However, 3.1 and 4.2% of the patients had CHF due to AC-based chemotherapy and non-AC followed by T, respectively. The median times to occurrence of CHF were different according to adjuvant treatments, approximately 2 years (701.0 days) in the AC-based chemotherapy group vs 1 year (377.5 days) AC followed by T group. T therapy was associated with earlier development of CHF irrespective of previous chemotherapy, but late risk of CHF 1.2 years after T therapy rapidly decreased in both chemotherapy groups. Multivariate Cox regression analysis revealed that the adjusted hazard ratio for CHF was increased in the group of older patients (≥ 65 years old) who underwent AC followed by T therapy, with Charlson comorbidity index scores of ≥ 2.

Conclusions

Our study showed that neo-/adjuvant chemotherapy using T irrespective of previous chemotherapy (AC or non-AC) was associated with significantly increased risk of CHF compared with AC-based chemotherapy in Korean patients with early breast cancer.

https://ift.tt/2K1ROuu

A Genomewide Integrative Analysis of GWAS and eQTLs Data Identifies Multiple Genes and Gene Sets Associated with Obesity

To identify novel susceptibility genes and gene sets for obesity, we conducted a genomewide expression association analysis of obesity via integrating genomewide association study (GWAS) and expression quantitative trait loci (eQTLs) data. GWAS summary data of body mass index (BMI) and waist-to-hip ratio (WHR) was driven from a published study, totally involving 339,224 individuals. The eQTLs dataset (containing 927,753 eQTLs) was obtained from eQTLs meta-analysis of 5,311 subjects. Integrative analysis of GWAS and eQTLs data was conducted by SMR software. The SMR single gene analysis results were further subjected to gene set enrichment analysis (GSEA) for identifying obesity associated gene sets. A total of 13,311 annotated gene sets were analyzed in this study. SMR single gene analysis identified 20 BMI associated genes (TUFM, SPI1, APOB48R, etc.). Also 3 WHR associated genes were detected (CPEB4, WARS2, and L3MBTL3). The significant association between Chr16p11 and BMI was observed by GSEA (FDR adjusted value = 0.040). The TGCTGCT, MIR-15A, MIR-16, MIR-15B, MIR-195, MIR-424, and MIR-497 (FDR adjusted value = 0.049) gene set appeared to be linked with WHR. Our results provide novel clues for the genetic mechanism studies of obesity. This study also illustrated the good performance of SMR for susceptibility gene mapping.

https://ift.tt/2FVhcQd

Lung Involvements in Rheumatic Diseases: Update on the Epidemiology, Pathogenesis, Clinical Features, and Treatment

Lung illness encountered in patients with rheumatic diseases bears clinical significance in terms of increased morbidity and mortality as well as potential challenges placed on patient care. Although our understanding of natural history of this important illness is still limited, epidemiologic knowledge has been accumulated during the past decade to provide useful information on the risk factors and prognosis of lung involvements in rheumatic diseases. Moreover, the pathogenesis particularly in the context of genetics has been greatly updated for both the underlying rheumatic disease and associated lung involvement. This review will focus on the current update on the epidemiologic and genetics features and treatment options of the lung involvements associated with four major rheumatic diseases (rheumatoid arthritis, systemic sclerosis, myositis, and systemic lupus erythematosus), with more attention to a specific form of involvement or interstitial lung disease.

https://ift.tt/2jGYAur

Progression of regional grey matter atrophy in multiple sclerosis

Abstract

Grey matter atrophy is present from the earliest stages of multiple sclerosis, but its temporal ordering is poorly understood. We aimed to determine the sequence in which grey matter regions become atrophic in multiple sclerosis and its association with disability accumulation. In this longitudinal study, we included 1417 subjects: 253 with clinically isolated syndrome, 708 with relapsing-remitting multiple sclerosis, 128 with secondary-progressive multiple sclerosis, 125 with primary-progressive multiple sclerosis, and 203 healthy control subjects from seven European centres. Subjects underwent repeated MRI (total number of scans 3604); the mean follow-up for patients was 2.41 years (standard deviation = 1.97). Disability was scored using the Expanded Disability Status Scale. We calculated the volume of brain grey matter regions and brainstem using an unbiased within-subject template and used an established data-driven event-based model to determine the sequence of occurrence of atrophy and its uncertainty. We assigned each subject to a specific event-based model stage, based on the number of their atrophic regions. Linear mixed-effects models were used to explore associations between the rate of increase in event-based model stages, and T₂ lesion load, disease-modifying treatments, comorbidity, disease duration and disability accumulation. The first regions to become atrophic in patients with clinically isolated syndrome and relapse-onset multiple sclerosis were the posterior cingulate cortex and precuneus, followed by the middle cingulate cortex, brainstem and thalamus. A similar sequence of atrophy was detected in primary-progressive multiple sclerosis with the involvement of the thalamus, cuneus, precuneus, and pallidum, followed by the brainstem and posterior cingulate cortex. The cerebellum, caudate and putamen showed early atrophy in relapse-onset multiple sclerosis and late atrophy in primary-progressive multiple sclerosis. Patients with secondary-progressive multiple sclerosis showed the highest event-based model stage (the highest number of atrophic regions, P < 0.001) at the study entry. All multiple sclerosis phenotypes, but clinically isolated syndrome, showed a faster rate of increase in the event-based model stage than healthy controls. T₂ lesion load and disease duration in all patients were associated with increased event-based model stage, but no effects of disease-modifying treatments and comorbidity on event-based model stage were observed. The annualized rate of event-based model stage was associated with the disability accumulation in relapsing-remitting multiple sclerosis, independent of disease duration (P < 0.0001). The data-driven staging of atrophy progression in a large multiple sclerosis sample demonstrates that grey matter atrophy spreads to involve more regions over time. The sequence in which regions become atrophic is reasonably consistent across multiple sclerosis phenotypes. The spread of atrophy was associated with disease duration and with disability accumulation over time in relapsing-remitting multiple sclerosis.

https://ift.tt/2Imveje

Emerging Tracers for Nuclear Cardiac PET Imaging

Abstract

Myocardial perfusion imaging using positron emission tomography (PET) has several advantages over single photon emission computed tomography (SPECT). The recent advances in SPECT technology have shown promise, but there is still a large need for PET in the clinical management of coronary artery disease (CAD). Especially, absolute quantification of myocardial blood flow (MBF) using PET is extremely important. In spite of considerable advances in the diagnosis of CAD, novel PET radiopharmaceuticals remain necessary for the diagnosis of CAD because clinical use of current cardiac radiotracers is limited by their physical characteristics, such as decay mode, emission energy, and half-life. Thus, the use of a radioisotope that has proper characteristics and a proper half-life to develop myocardial perfusion agents could overcome these limitations. In this review, the current state of cardiac PET and a general overview of novel ¹⁸F or ⁶⁸Ga-labeled radiotracers, including their radiosynthesis, in vivo characterization, and evaluation, are provided. The future perspectives are discussed in terms of their potential usefulness based on new image analysis methods and hybrid imaging.

https://ift.tt/2KHwjAm

Development and validation of a difficulty score to predict intraoperative complications during laparoscopic liver resection

British Journal of Surgery, EarlyView.


https://ift.tt/2jH0MCw

Delay in starting radiotherapy due to neoadjuvant therapy does not worsen survival in unresected glioblastoma patients

Abstract

Purpose

We retrospectively examined the potential effect on overall survival (OS) of delaying radiotherapy to administer neoadjuvant therapy in unresected glioblastoma patients.

Patients and methods

We compared OS in 119 patients receiving neoadjuvant therapy followed by standard treatment (NA group) and 96 patients receiving standard treatment without neoadjuvant therapy (NoNA group). The MaxStat package of R identified the optimal cut-off point for waiting time to radiotherapy.

Results

OS was similar in the NA and NoNA groups. Median waiting time to radiotherapy after surgery was 13 weeks for the NA group and 4.2 weeks for the NoNA group. The longest OS was attained by patients who started radiotherapy after 12 weeks and the shortest by patients who started radiotherapy within 4 weeks (12.3 vs 6.6 months) (P = 0.05). OS was 6.6 months for patients who started radiotherapy before the optimal cutoff of 6.43 weeks and 19.1 months for those who started after this time (P = 0.005). Patients who completed radiotherapy had longer OS than those who did not, in all 215 patients and in the NA and NoNA groups (P = 0.000). In several multivariate analyses, completing radiotherapy was a universally favorable prognostic factor, while neoadjuvant therapy was never identified as a negative prognostic factor.

Conclusion

In our series of unresected patients receiving neoadjuvant treatment, in spite of the delay in starting radiotherapy, OS was not inferior to that of a similar group of patients with no delay in starting radiotherapy.

https://ift.tt/2FUGkGS