OBJECTIVES
According to the EuroSCORE-II criteria, patients undergoing emergency coronary artery bypass grafting (CABG) are operated on before the beginning of the next working day after decision to ...operate while salvage CABG patients require cardiopulmonary resuscitation en route to the operating theatre. The objective of this multicentre study was to investigate the efficacy of emergency and salvage CABG.
METHODS
A retrospective analysis of all patients that underwent emergency or salvage CAGB at four North-European university hospitals from 2006 to 2014.
RESULTS
A total of 614 patients; 580 emergency and 34 salvage CABG patients (mean age 67 ± 10 years, 56% males) were included. All patients had an acute coronary syndrome: 234 (38%) had an ST segment elevation myocardial infarction (STEMI) and 289 (47%) had a non-STEMI. Haemodynamic instability requiring inotropic drugs and/or intra-aortic balloon pump preoperatively occurred in 87 (14%) and 82 (13%) of the patients, respectively. Three hundred and thirty-one patient (54%) were transferred to the operating room immediately after angiography and 205 (33%) had a failure of an attempted percutaneous coronary intervention. Cardiopulmonary resuscitation within 1 h before the operation was performed in 49 patients (8%), and 9 patients (1%) received cardiac massage during sternotomy. Hospital mortality for emergency and salvage operations was 13 and 41%, respectively. Early complications included reoperation for bleeding (15%), postoperative stroke (6%) and de novo dialysis for acute kidney injury (6%). Overall 5-year survival rate was 79% for emergency operations and 46% for salvage operations. Only one out of 9 patients receiving cardiac massage during sternotomy survived.
CONCLUSIONS
Early mortality in patients undergoing emergent and salvage CABG is substantial, especially in salvage patients. Long-term survival is acceptable in both emergent and salvage patients. Life-saving emergency and salvage CABG is justified in most patients but salvage patients have dismal prognosis if cardiac massage is needed during sternotomy.
A comprehensive characterization of blood proteome profiles in cancer patients can contribute to a better understanding of the disease etiology, resulting in earlier diagnosis, risk stratification ...and better monitoring of the different cancer subtypes. Here, we describe the use of next generation protein profiling to explore the proteome signature in blood across patients representing many of the major cancer types. Plasma profiles of 1463 proteins from more than 1400 cancer patients are measured in minute amounts of blood collected at the time of diagnosis and before treatment. An open access Disease Blood Atlas resource allows the exploration of the individual protein profiles in blood collected from the individual cancer patients. We also present studies in which classification models based on machine learning have been used for the identification of a set of proteins associated with each of the analyzed cancers. The implication for cancer precision medicine of next generation plasma profiling is discussed.
The tall cell variant (TCV) of papillary thyroid carcinoma (PTC) is an aggressive variant of PTC that is believed to have worse outcomes than classical PTC. The objective of this study was to ...investigate the incidence, survival, and disease recurrence of patients with TCV and compare them with other PTC in a whole population.
Information on all thyroid carcinomas diagnosed in Iceland from 1990 to 2009 was obtained from the Icelandic Cancer Registry. PTC diagnosed postmortem was excluded. The date of diagnosis, sex, and age at diagnosis were registered. All histopathology material was re-evaluated, and papillary thyroid tumors classified as either TCV or other types of PTC. Tumors were classified as TCV if >50% of cells were tall (height > twice the width). TNM stage was determined for all the cases. Endpoints were thyroid cancer-specific death and thyroid cancer recurrence.
Out of 376 patients diagnosed with PTC in the study period, 49 (13%) were classified as TCV. Patients with TCV were older (66 years vs. 49 years, p<0.001), more often had pT4 tumors (71% vs. 15%, p<0.001), had higher rates of nodal metastasis (51% vs. 22%, p<0.001), and more often distant metastasis (14% vs. 2%, p<0.001). The age-adjusted incidence of TCV for men was 0.5/100,000 confidence interval (CI) 0.3-0.7 and for women 0.7/100,000 CI 0.4-1.0 between 1990 and 2009. The five-year disease-specific survival for TCV was 83% CI 68-91 compared to 98% CI 96-99 for other PTC respectively (p<0.001). In multivariate analysis, TCV histology was an independent risk factor for recurrence (hazard ratio (HR) 3.18 CI 1.48-6.84) but not for disease specific survival (HR 1.86 CI 0.77-4.73).
TCV comprises 13% of all diagnosed PTC in Iceland with an incidence of 0.5/100,000 for men and 0.7/100,000 for women. Patients diagnosed with TCV have worse five-year disease-specific survival than patients with other PTC. TCV histology is an independent risk factor for disease recurrence but not for disease-specific survival.
Papillary renal cell carcinoma (pRCC) is the second most common histology of renal cell carcinoma (RCC), accounting for 10-15% of cases. Traditionally, pRCC is divided into type 1 and type 2, ...although this division is currently debated as a prognostic factor of survival. Our aim was to investigate the epidemiology and survival of the pRCC subtypes in a whole nation cohort of patients during a 50-year period.
A Population based retrospective study including consecutive cases of RCC in Iceland from 1971-2020. Comparisons were made between histological classifications of RCC, with emphasis on pRCC subtypes (type 1 vs. 2) for outcome estimation. Changes in RCC incidence were analyzed in 5-year intervals after age standardization. The Kaplan-Meier method and Cox regression were used for outcome analysis.
A total of 1.725 cases were identified, with 74.4%, 2.1% and 9.2% having clear cell (ccRCC), chromophobe (chRCC), and pRCC, respectively. The age standardized incidence (ASI) of pRCC was 1.97/100.000 for males and 0.5/100.000 for females, and the proportion of pRCC increased from 3.7% to 11.5% between the first and last intervals of the study (p < 0.001). Age standardized cancer specific mortality (ASCSM) of pRCC was 0.6/100.000 and 0.19/100.000 for males and females, respectively. The annual average increase in ASI was 3.6% for type 1 pRCC, but the ASI for type 2 pRCC and ASCSM for both subtypes did not change significantly. Male to female ratio was 4.4 for type 1 pRCC and 2.3 for type 2. The average tumor size for type 1 and 2 was 58.8 and 73.7 mm, respectively. Metastasis at diagnosis was found in 8.7% in the type 1 pRCC, compared to 30.0% of patients with type 2 pRCC (p < 0.001). Estimated 5-year cancer-specific survival (CSS) were 94.4%, 80.7%, and 69.3% for chRCC, pRCC and ccRCC, respectively (p < 0.001). For the pRCC subtypes, type 1 was associated with better 5-year CSS than type 2 (86.3% vs. 66.0%, p < 0.001), although this difference was not significant after adjusting for cancer stage and grading.
pRCC histology was slightly less common in Iceland than in other countries. Males are more than three times more likely to be diagnosed with pRCC, compared to other RCC histologies. The subtype of pRCC was not found to be an independent risk factor for worse survival, and as suggested by the most recent WHO Classification of Urinary Tumors, grade and TNM-stage seem to be the most important factors for estimation of survival for pRCC patients.
Dioxin exposure has experimentally been associated with changes in DNA methylation, an epigenetic change that is associated with disease. The present study aims to investigate if serum levels of ...dioxin and other persistent environmental pollutants are related to global DNA methylation in a human sample. In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (all aged 70), global DNA methylation was measured by the Luminometric Methylation Assay in 524 subjects. Twenty-three different POPs, including 16 PCBs, five pesticides, one dioxin (OCDD) and one brominated flame retardant (BDE47) were analysed by HRGC/HRMS. Ten single nucleotide polymorphisms (SNPs) in the Aryl hydrocarbon (Ah)-receptor were analysed by mini-sequencing. High levels of toxic equivalency (TEQ) for PCBs and dioxin were associated with DNA hypermethylation (p=0.030). This was mainly attributed to coplanar non-ortho PCBs. While no significant associations were found between DNA methylation and SNPs in the Ah-receptor, an interaction was found between the SNP rs2237297 and TEQ so that TEQ was associated with hypermethylation (p=0.009) only in subjects with one G-allele (n=103). Also high levels of the PCB126 congener, the OCDD, and the pesticide metabolite p,p′-DDE were related to DNA hypermethylation (p=0.01, 0.03 and 0.003, respectively). In conclusion, in a sample of elderly subjects, high TEQ including PCBs and the dioxin OCDD and high serum levels of PCB126, OCDD, and p,p′-DDE were related to global DNA hypermethylation in a cross-sectional analysis.
•We investigated the association between POPs and global DNA methylation.•Cross sectional data from a cohort of elderly were analysed.•The main exposure was toxic equivalency including PCBs and the dioxin OCDD.•High toxic equivalency was related to global DNA hypermethylation.
Genetic polymorphisms in vitamin D metabolism and signaling genes have been inconsistently associated with risk of breast cancer, though few studies have examined SNPs in vitamin D-related genes ...other than the vitamin D receptor (VDR) gene and particularly have not examined the association with the retinoid X receptor alpha (RXRA) gene which may be a key vitamin D pathway gene. We conducted a nested case-control study of 734 cases and 1435 individually matched controls from a population-based prospective cohort study, the Northern Sweden Mammary Screening Cohort. Tag and functional SNPs were genotyped for the VDR, cytochrome p450 24A1 (CYP24A1), and RXRA genes. We also genotyped specific SNPs in four other genes related to vitamin D metabolism and signaling (GC/VDBP, CYP2R1, DHCR7, and CYP27B1). SNPs in the CYP2R1, DHCR7, and VDBP gene regions that were associated with circulating 25(OH)D concentration in GWAS were also associated with plasma 25(OH)D in our study (p-trend <0.005). After taking into account the false discovery rate, these SNPs were not significantly associated with breast cancer risk, nor were any of the other SNPs or haplotypes in VDR, RXRA, and CYP24A1. We observed no statistically significant associations between polymorphisms or haplotypes in key vitamin D-related genes and risk of breast cancer. These results, combined with the observation in this cohort and most other prospective studies of no association of circulating 25(OH)D with breast cancer risk, do not support an association between vitamin D and breast cancer risk.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Drug-induced agranulocytosis is a potentially life-threatening adverse reaction. Genome-wide association studies (GWASs) in ethnic Chinese people in Taiwan and Hong Kong have shown an association ...between agranulocytosis induced by antithyroid drugs and the HLA alleles HLA-B*38:02 and HLA-DRB1*08:03. We aimed to identify genetic variants associated with antithyroid drug-induced agranulocytosis in a white European population.
We did a GWAS in 234 European adults with any non-chemotherapy drug-induced agranulocytosis (absolute neutrophil count ≤0·5 × 10(9)/L ≤500/μL) and 5170 population controls. 39 of the 234 patients had agranulocytosis that was induced by antithyroid drugs (thiamazole methimazole, carbimazole, or propylthiouracil). After imputation and HLA allele prediction, 9 380 034 single nucleotide polymorphisms (SNPs) and 180 HLA alleles were tested for association. The genome-wide significance threshold was p<5 × 10(-8).
Agranulocytosis induced by non-chemotherapy drugs in general was significantly associated with the HLA region on chromosome 6, with odds ratios (ORs) of 3·24 (95% CI 2·31-4·55, p=1·20 × 10(-11)) for HLA-B*27:05 and 3·57 (2·61-4·90, p=2·32 × 10(-15)) for the top SNP (rs114291795). Drug-specific analysis showed that the association with HLA-B*27:05 was largely driven by cases induced by antithyroid drugs. In a multiple logistic regression model, the OR for HLA-B*27:05 was 7·30 (3·81-13·96) when antithyroid drug-induced agranulocytosis was compared with population controls (p=1·91 × 10(-9)) and 16·91 (3·44-83·17) when compared with a small group of hyperthyroid controls (p=5·04 × 10(-4)). Three SNPs were strongly associated with antithyroid drug-induced agranulocytosis: rs652888 (OR 4·73, 95% CI 3·00-7·44, p=1·92 × 10(-11)) and rs199564443 (17·42, 7·38-41·12, p=7·04 × 10(-11)), which were independent of HLA-B*27:05, and rs1071816 (5·27, 3·06-9·10, p=2·35 × 10(-9)) which was in moderate linkage disequilibrium with HLA-B*27:05. In heterozygous carriers of all three SNPs, the predicted probability of antithyroid drug-induced agranulocytosis was about 30% (OR 753, 95% CI 105-6812). To avoid one case of agranulocytosis, based on the possible risk reduction if all three SNPs are genotyped and carriers are treated or monitored differently from non-carriers, roughly 238 patients would need to be genotyped.
In white European people, antithyroid drug-induced agranulocytosis was associated with HLA-B*27:05 and with other SNPs on chromosome 6. In the future, carriers of these variants could be placed under intensified monitoring or offered alternative treatment for hyperthyroidism.
Swedish Research Council, Swedish Heart and Lung Foundation, Clinical Research Support at Uppsala University, German Federal Institute for Drugs and Medical Devices, Carlos III Spanish Health Institute, European Regional Development Fund, UK National Institute for Health Research, The Selander's Foundation, Thuréus Foundation, European Commission, and Science for Life Laboratory.
Ovarian cancer is the eighth most common cancer among women and has a 5-year survival of only 30-50%. The survival is close to 90% for patients in stage I but only 20% for patients in stage IV. The ...presently available biomarkers have insufficient sensitivity and specificity for early detection and there is an urgent need to identify novel biomarkers.
We employed the Explore PEA technology for high-precision analysis of 1463 plasma proteins and conducted a discovery and replication study using two clinical cohorts of previously untreated patients with benign or malignant ovarian tumours (
= 111 and
= 37).
The discovery analysis identified 32 proteins that had significantly higher levels in malignant cases as compared to benign diagnoses, and for 28 of these, the association was replicated in the second cohort. Multivariate modelling identified three highly accurate models based on 4 to 7 proteins each for separating benign tumours from early-stage and/or late-stage ovarian cancers, all with AUCs above 0.96 in the replication cohort. We also developed a model for separating the early-stage from the late-stage achieving an AUC of 0.81 in the replication cohort. These models were based on eleven proteins in total (ALPP, CXCL8, DPY30, IL6, IL12, KRT19, PAEP, TSPAN1, SIGLEC5, VTCN1, and WFDC2), notably without MUCIN-16. The majority of the associated proteins have been connected to ovarian cancer but not identified as potential biomarkers.
The results show the ability of using high-precision proteomics for the identification of novel plasma protein biomarker candidates for the early detection of ovarian cancer.
Background Bipolar affective disorder (BPAD) and schizophrenia (SZ) are devastating psychiatric disorders that each affect about 1% of the population worldwide. Identification of new drug targets is ...an important step toward better treatment of these poorly understood diseases. Methods Genome-wide copy number variation (CNV) was assessed and variants were ranked by co-occurrence with disease in 48 BPAD families. Additional support for involvement of the highest-ranking CNV from the family-based analysis in psychiatric disease was obtained through analysis of 4084 samples with BPAD, SZ, or schizoaffective disorder. Finally, a pooled analysis of in-house and published datasets was carried out including 10,925 cases with BPAD, SZ, or schizoaffective disorder and 16,747 controls. Results In the family-based analysis, an approximately 200 kilobase (kb) deletion in the first intron of the MAGI1 gene was identified that segregated with BPAD in a pedigree (six out of six affected individuals; parametric logarithm of the odds score = 1.14). In the pooled analysis, seven additional insertions or deletions over 100 kb were identified in MAGI1 in cases, while only two such CNV events were identified in the same gene in controls ( p = .023; Fisher's exact test). Because earlier work had identified a CNV in the close relative MAGI2 in SZ, the study was extended to include MAGI2 . In the pooled analysis of MAGI2, two large deletions were found in cases, and two duplications were detected in controls. Conclusions Results presented herein provide further evidence for a role of MAGI1 and MAGI2 in BPAD and SZ etiology.
Objectives: We studied the incidence and risk factors of reoperation for bleeding following CABG in a nationwide cohort with focus on long-term complications and survival. Design: A retrospective ...study on 2060 consecutive, isolated CABG patients operated 2001-2016. Outcome of reoperated patients (n = 130) were compared to non-reoperated ones (n = 1930), including major adverse cardiac and cerebrovascular events (MACCE) and overall survival. Risk factors for reoperation were determined using multivariate logistic regression and a Cox proportional hazards model to assess prognostic factors of long-term survival. Median follow-up was 7.6 years. Results: One hundred thirty patients (6.3%) were reoperated with an annual decrease of 4.1% per year over the study period (p=.04). Major complications (18.5 vs. 9.6%) and 30-day mortality (8.5 vs. 1.9%,) were higher in the reoperation group (p<.001). The use of clopidogrel preoperatively (OR 3.62, 95% CI: 1.90-6.57) and reduced left ventricular ejection fraction (OR 2.23, 95% CI: 1.25-3.77) were the strongest predictors of reoperation, whereas off-pump surgery was associated with a lower reoperation risk (OR 0.44, 95% CI: 0.22-0.85). After exluding patients that died within 30 days postoperatively, no difference in long-term survival or freedom from MACCE was found between groups, and reoperation was not an independent risk factor for long-term mortality in multivariate analysis. Conclusions: The reoperation rate in this study was relatively high but decreased significantly over time. Reoperation was associated with twofold increased risk for major complications and fourfold 30-day mortality, but comparable long-term MACCE and survival rates. This implies that if patients survive the first 30 days following reoperation, their long-term outcome is comparable to non-reoperated patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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