| 1. |
- Zhu, Zheng, et al.
(författare)
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TOMM40 and APOE variants synergistically increase the risk of Alzheimer's disease in a Chinese population
- 2021
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Ingår i: Aging Clinical and Experimental Research. - : Springer. - 1594-0667 .- 1720-8319. ; 33:6, s. 1667-1675
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Tidskriftsartikel (refereegranskat)abstract
- Background: The apolipoprotein E (APOE) epsilon 4 allele is a strong risk factor for Alzheimer's disease (AD) in Caucasian and African American populations. It suggests that other genetic factors may modulate AD pathogenesis in Chinese populations, among which the frequency of this allele is reduced but the AD prevalence is maintained. The translocase of outer mitochondrial membrane 40 (TOMM40), which is located adjacent to APOE,may play an APOE-dependent role in modulating AD pathogenesis.Aims: This work aimed to investigate whether TOMM40 polymorphisms modulate AD risk independently of, or in conjunction with APOE polymorphisms in Chinese populations.Methods: We conducted a case-control study including 834 patients with AD recruited from the Memory Clinic and 643 cognitively normal participants recruited from the community. The Taqman SNP method was used for APOE genotyping, while TOMM40 polymorphism genotyping was conducted via a polymerase chain reaction-ligase detection reaction.Results: TheTOMM40 rs10119 and rs71352238 alleles were associated with AD independently of the patient APO status. The rs10119 AA genotype and rs71352238 CC genotype were risk genotypes of AD. Individuals carrying a TOMM40 rs10119 GG/APOE epsilon 4+ (OR, 3.73; 95% CI 1.49-9.37;P = 0.005), TOMM40 rs10119 AG/APOE epsilon 4+ (OR, 4.16; 95% CI 3.30-5.24;P < 0.001), or TOMM40 rs10119 AA/APOE epsilon 4+ (OR, 14.78; 95% CI 8.56-25.54;P < 0.001) genotype exhibited a significantly higher AD risk. Those carrying a TOMM40 rs71352238 TT/APOE epsilon 4+ (OR, 3.82; 95% CI 2.32-6.29;P < 0.001), TOMM40 rs71352238 CT/APOE epsilon 4+ (OR, 4.40; 95% CI 3.46-5.56;P < 0.001), or TOMM40 rs71352238 CC/APOE epsilon 4+ (OR, 14.02; 95% CI 7.81-25.17;P < 0.001) genotype also exhibited a significantly increased AD risk.Discussion and conclusions: This study provides invaluable insights into the mechanisms underlying the prevalence of AD in Chinese populations, and supports that simultaneous TOMM40 and APOE genotyping in the clinical setting may identify individuals at high risk of developing AD.
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| 2. |
- Brand, Judith, 1984-, et al.
(författare)
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Maternal smoking during pregnancy and fractures in offspring : national register based sibling comparison study
- 2020
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Ingår i: The BMJ. - : BMJ Publishing Group Ltd. - 1756-1833. ; 368
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To study the impact of maternal smoking during pregnancy on fractures in offspring during different developmental stages of life.DESIGN: National register based birth cohort study with a sibling comparison design.SETTING: Sweden.PARTICIPANTS: 1 680 307 people born in Sweden between 1983 and 2000 to women who smoked (n=377 367, 22.5%) and did not smoke (n=1 302 940) in early pregnancy. Follow-up was until 31 December 2014.MAIN OUTCOME MEASURE: Fractures by attained age up to 32 years.RESULTS: During a median follow-up of 21.1 years, 377 970 fractures were observed (the overall incidence rate for fracture standardised by calendar year of birth was 11.8 per 1000 person years). The association between maternal smoking during pregnancy and risk of fracture in offspring differed by attained age. Maternal smoking was associated with a higher rate of fractures in offspring before 1 year of age in the entire cohort (birth year standardised fracture rates in those exposed and unexposed to maternal smoking were 1.59 and 1.28 per 1000 person years, respectively). After adjustment for potential confounders the hazard ratio for maternal smoking compared with no smoking was 1.27 (95% confidence interval 1.12 to 1.45). This association followed a dose dependent pattern (compared with no smoking, hazard ratios for 1-9 cigarettes/day and >= 10 cigarettes/day were 1.20 (95% confidence interval 1.03 to 1.39) and 1.41 (1.18 to 1.69), respectively) and persisted in within-sibship comparisons although with wider confidence intervals (compared with no smoking, 1.58 (1.01 to 2.46)). Maternal smoking during pregnancy was also associated with an increased fracture incidence in offspring from age 5 to 32 years in whole cohort analyses, but these associations did not follow a dose dependent gradient. In within-sibship analyses, which controls for confounding by measured and unmeasured shared familial factors, corresponding point estimates were all close to null. Maternal smoking was not associated with risk of fracture in offspring between the ages of 1 and 5 years in any of the models.CONCLUSION: Prenatal exposure to maternal smoking is associated with an increased rate of fracture during the first year of life but does not seem to have a long lasting biological influence on fractures later in childhood and up to early adulthood.
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| 3. |
- Cao, Yang, Associate Professor, 1972-, et al.
(författare)
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COVID-19 case-fatality rate and demographic and socioeconomic influencers : worldwide spatial regression analysis based on country-level data
- 2020
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 10:11
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the influence of demographic and socioeconomic factors on the COVID-19 case-fatality rate (CFR) globally.DESIGN: Publicly available register-based ecological study.SETTING: Two hundred and nine countries/territories in the world.PARTICIPANTS: Aggregated data including 10 445 656 confirmed COVID-19 cases.PRIMARY AND SECONDARY OUTCOME MEASURES: COVID-19 CFR and crude cause-specific death rate were calculated using country-level data from the Our World in Data website.RESULTS: The average of country/territory-specific COVID-19 CFR is about 2%-3% worldwide and higher than previously reported at 0.7%-1.3%. A doubling in size of a population is associated with a 0.48% (95% CI 0.25% to 0.70%) increase in COVID-19 CFR, and a doubling in the proportion of female smokers is associated with a 0.55% (95% CI 0.09% to 1.02%) increase in COVID-19 CFR. The open testing policies are associated with a 2.23% (95% CI 0.21% to 4.25%) decrease in CFR. The strictness of anti-COVID-19 measures was not statistically significantly associated with CFR overall, but the higher Stringency Index was associated with higher CFR in higher-income countries with active testing policies (regression coefficient beta=0.14, 95% CI 0.01 to 0.27). Inverse associations were found between cardiovascular disease death rate and diabetes prevalence and CFR.CONCLUSION: The association between population size and COVID-19 CFR may imply the healthcare strain and lower treatment efficiency in countries with large populations. The observed association between smoking in women and COVID-19 CFR might be due to the finding that the proportion of female smokers reflected broadly the income level of a country. When testing is warranted and healthcare resources are sufficient, strict quarantine and/or lockdown measures might result in excess deaths in underprivileged populations. Spatial dependence and temporal trends in the data should be taken into account in global joint strategy and/or policy making against the COVID-19 pandemic.
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| 4. |
- Dehlaghi Jadid, Kaveh, 1985-, et al.
(författare)
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Long term oncological outcomes for laparoscopic versus open surgery for rectal cancer - A population-based nationwide noninferiority study
- 2022
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Ingår i: Colorectal Disease. - : Wiley. - 1462-8910 .- 1463-1318. ; 24:11, s. 1308-1317
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Tidskriftsartikel (refereegranskat)abstract
- Aim The aim of this work was to compare the 5-year overall survival in a national cohort of patients undergoing curative abdominal resection for rectal cancer by laparoscopic (LAP) or open (OPEN) surgery. Method All patients diagnosed with clinical Stage I-III rectal cancer and who underwent LAP or OPEN abdominal curative surgery in Sweden between 2010 and 2016 were retrieved from the Swedish Colorectal Cancer Registry. A noninferiority study design was employed with a statistical power of 90%, a one-side type I error of 2.5% and a noninferiority margin of 2%. The analyses were performed as intention-to-treat and the relationship between surgical technique and overall mortality within 5 years was analysed. Multilevel regression models with the patients matched by propensity scores adjusted for patient- and tumour-related variables were used. Results A total of 8410 Stage I-III cancer patients were included. This group underwent 2094 LAP (24.9%) and 6316 OPEN (75.1%) procedures and were followed until 31 December 2020. Multivariable Cox regression demonstrated that 5-year overall survival was higher in the LAP group [hazard ratio (HR) 0.877; 95% CI 0.877-0.993]. The outcome was similar when multiple imputation and propensity score matching were employed. When cT4 patients were excluded there was no difference (HR 0.885; 95% CI 0.790-1.033). At 5-years' follow-up local recurrence was not different, at 2.9% for the LAP group and 3.6% for the OPEN group (p = 0.075), while metastatic disease was more frequent in the OPEN group (19.6% compared with 15.6% for LAP; p < 0.001). Conclusion This study demonstrated that the LAP technique was not inferior to OPEN surgery with regard to overall 5-year survival. These results support the use of laparoscopic surgery.
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| 5. |
- Dehlaghi Jadid, Kaveh, 1985-, et al.
(författare)
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Long-term oncological outcomes for minimally invasive surgery versus open surgery for colon cancer-a population-based nationwide study with a non-inferiority design
- 2023
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Ingår i: Colorectal Disease. - : Wiley. - 1462-8910 .- 1463-1318. ; 25:5, s. 954-963
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Tidskriftsartikel (refereegranskat)abstract
- AimThe study aimed to compare 5-year overall survival in a national cohort of patients undergoing curative abdominal resection for colon cancer by minimally invasive surgery (MIS) or by the open (OPEN) technique. MethodsAll patients diagnosed between 2010 and 2016 in Sweden with pathological Union International Contre le Cancer Stages I-III colon cancer localized in the caecum, ascending colon, hepatic flexure or sigmoid colon and those who underwent curative right sided hemicolectomy, sigmoid resection or high anterior resection by MIS or OPEN were included. Patients were identified in the Swedish Colorectal Cancer Registry from which all data were retrieved. The analyses were performed as intention-to-treat and the relationship between surgical technique (MIS or OPEN) and overall mortality within 5 years was analysed. For the primary research question a non-inferiority hypothesis was assumed with a statistical power of 90%, a one-side type I error of 2.5% and a non-inferiority margin of 2%. For the secondary analyses, multilevel survival regression models with the patients matched by propensity scores were employed, adjusted for patient- and tumour-related variables. ResultsA total of 11 605 pathological Union International Contre le Cancer Stages I-III patients were included with 3297 MIS (28.4%) and 8308 OPEN (71.6%) and were followed until 31 December 2020. The primary analysis demonstrated superiority for MIS compared to OPEN. The multilevel survival regression analyses confirmed that 5-year overall survival was higher in MIS with a hazard ratio of 0.874 (95% confidence interval 0.791-0.965), and if excluding pT4 the outcome was similar, with a hazard ratio of 0.847 (95% confidence interval 0.756-0.948). ConclusionThis observational study demonstrated that MIS was favourable to OPEN with regard to 5-year overall survival. These results support the use of laparoscopic colon cancer surgery in routine practice.
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| 6. |
- Ferrari, Gabriele, 1984-, et al.
(författare)
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Long-term results of percutaneous coronary intervention in no-touch vein grafts are significantly better than in conventional vein grafts
- 2024
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Ingår i: Perfusion. - London : Sage Publications. - 0267-6591 .- 1477-111X.
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Conventional vein grafts have a high risk of thrombosis and early atherosclerosis. Percutaneous coronary intervention (PCI) in conventional vein grafts is associated with a higher incidence of late adverse cardiac events. The aim of this study was to evaluate the long-term results after PCI in saphenous vein grafts (SVG) harvested with the no-touch technique compared to the conventional technique. Methods: This was a single-center, retrospective, cohort study, based on data from the Swedeheart register. The inclusion criterion was individuals who underwent CABG using different vein graft techniques between January 1992 and July 2020, and who required a PCI in SVGs between January 2006 and July 2020. The primary end point was long-term in-stent restenosis. The secondary endpoints were long-term major adverse cardiac events (MACE) and 1-year re-hospitalization rates. The associations between the graft types and the endpoints were evaluated using the Fine and Gray competing-risk regression analysis. Results: The study included 346 individuals (67 no-touch, 279 conventional). The mean clinical follow-up time was 6.4 years with a standard deviation of 3.7 years. The long-term in-stent restenosis rate for the no-touch grafts was 3.2% compared to 18.7% for the conventional grafts (p <.01), with a subdistribution hazard ratio (SHR) of 0.16 (p =.010). The long-term MACE rate was 27.0% in the no-touch group and 48.3% in the conventional group (p <.01) with a SHR of 0.53 (p =.017). The short-term results were similar in both groups. Conclusions: Percutaneous coronary intervention in a no-touch vein graft was associated with statistically significantly fewer in-stent restenoses and MACE at long-term follow-up compared to a conventional SVG. © The Author(s) 2024.
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| 7. |
- Ferrari, Gabriele, 1984-, et al.
(författare)
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Percutaneous coronary intervention in saphenous vein grafts after coronary artery bypass grafting : a systematic review and meta-analysis
- 2021
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Ingår i: Scandinavian Cardiovascular Journal. - : Taylor & Francis. - 1401-7431 .- 1651-2006. ; 55:4, s. 245-253
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Forskningsöversikt (refereegranskat)abstract
- To investigate the results of percutaneous coronary intervention (PCI) in saphenous vein grafts after coronary artery bypass grafting (CABG). Design. MEDLINE, Embase, and the Cochrane library were searched for relevant articles published between 1 January 2000 and 29 February 2020. The PICO (population, intervention, comparison, outcome) model was applied in constructing the clinical question. Two independent researchers performed the literature search. Thirty-six articles were identified and subjected to a quality assessment. The primary outcomes of the meta-analysis were long-term in-stent restenosis and long-term major adverse cardiac events (MACE). Results. In-stent restenosis was 9.4% (95% CI: 4.2-14.7%) and MACE was 35.3% (95% CI: 27-43.7%) at mean time 2.7 ± 1.0 years. The secondary outcomes were the unsuccessful PCI rate (7.7%; 95% CI: 2.9-12.5%), 30-day MACE (4.3%; 95% CI: 2.5-6.1%), and 1-year MACE (15.5%; 95% CI: 11.7-19.3%). The use of drug-eluting stents resulted in better outcomes at least in term of in-stent restenosis, while the benefit of using embolic protection devices was questionable. Conclusions. PCI of a stenosed or occluded saphenous vein graft is a challenge for interventional cardiologists, and is still associated with relatively high rates of restenosis, MACE, and procedural failure. All efforts to enhance the results are warranted, including improved quality of the venous grafts used during CABG.
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| 8. |
- Ferrari, Gabriele, 1984-, et al.
(författare)
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Quality of Life After Percutaneous Coronary Intervention in No-Touch Saphenous Vein Grafts is Significantly Better Than in Conventional Vein Grafts
- 2022
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Ingår i: Brazilian Journal of Cardiovascular Surgery. - : Sociedade Brasileira de Cirurgia Cardiovascular. - 0102-7638 .- 1678-9741. ; 37:4, s. 430-438
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To compare health-related quality of life (HRQoL) of patients primarily treated with a no-touch saphenous vein graft with that of patients who received a conventional graft.METHODS: The study included all individuals treated with a percutaneous coronary intervention (PCI) on a saphenous vein graft (SVG) between January 2006 and June 2020. The RAND-36 health survey was used to assess HRQoL. The Mann-Whitney U test was used to test differences in HRQoL between the two groups. Effect size was estimated via Cohen's d. The average treatment effect between the groups was tested by propensity score matching (PSM).RESULTS: Of the 346 patients treated with a PCI in a stenosed or occluded SVG, 165 responded to RAND-36 (no-touch: n=48; conventional: n=117). Patients with a no-touch graft reported better mean values on seven of the eight health survey domains. Statistically significant differences were observed for four of the domains, all in favour of the no-touch group. The effect size estimates indicated a small difference for five domains, with the highest values (>0.40) seen for the general health and energy/fatigue domains. PSM confirmed a statistically significant difference for the physical functioning and general health domains.CONCLUSION: At a mean follow-up of 5.4 years, patients who received a PCI in no-touch vein grafts showed significantly better HRQoL than those who received a PCI in conventional vein grafts.
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| 9. |
- Grännö, O., et al.
(författare)
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Preclinical protein signatures in blood predict Crohn's disease and Ulcerative colitis several years before the diagnosis
- 2024
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Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 18:Suppl. 1, s. I660-I661
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: We aimed to identify protein signatures predictive of a future diagnosis of inflammatory bowel disease (IBD).Methods: We conducted a case-control study, nested within large population-based cohorts with biorepositories. Samples were obtained from individuals who later in life were diagnosed with IBD (preclinical cases) and compared with age and sex-matched individuals who remained free from IBD during follow-up (controls). Using proximity extension assays (Olink, Uppsala), we measured 176 proteins. We applied regularized logistic regression to identify protein signatures of preclinical disease in serum from the discovery cohort (n=312). Their performance was validated in an external preclinical cohort (n=222). The biological relevance of identified proteins was further assessed in an inception cohort (n=144). Finally, we used an IBD twin cohort (n=327) to examine the impact of genetic and shared environmental factors on identified proteins.Results: We identified 34 proteins associated with preclinical Crohn’s disease (CD) in the discovery cohort (Pfalse discovery rate <0.10), with 9 confirmed in the validation cohort (Pfalse discovery rate <0.05). For preclinical ulcerative colitis (UC), 45 proteins were identified and 12 validated (Fig. 1A-B). In the discovery cohort, a signature of 29 proteins differentiated preclinical CD cases from controls with an AUC of 0.85 (Fig. 1G). Its performance was confirmed when applied to the preclinical validation cohort (AUC=0.84, Fig. 1H). Moreover, the signature had excellent capacity to differentiate newly diagnosed CD from healthy controls in the inception cohort (AUC = 0.99, Fig. 1I). The preclinical UC signature had a significant, but albeit lower, predictive capacity in the discovery (AUC=0.77), validation (AUC=0.67) and inception cohort (AUC=0.90, Fig. 1G-I).15 of 17 proteins associated with preclinical IBD demonstrated significantly higher intra-pair correlation coefficients in healthy monozygotic- compared to dizygotic twin pairs, indicating an influence from genetic factors on the regulation of these protein markers. The preclinical signature for CD demonstrated an AUC of 0.87 when comparing twins with preclinical CD (n=10) to matched external healthy twins. However, its predictive capacity was lower when comparing preclinical CD twins with their healthy twin siblings (AUC=0.58), i.e., when accounting for genetic and shared environmental factors. The difference in AUC estimates in the twin cohort was not significant (P=0.07).
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| 10. |
- Han, Hedong, et al.
(författare)
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Morbid obesity is adversely associated with perioperative outcomes inpatients undergoing robot-assisted laparoscopic radical prostatectomy
- 2020
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Ingår i: Canadian Urological Association Journal (CUAJ). - : Canadian Medical Association. - 1911-6470 .- 1920-1214. ; 14:11, s. E574-E581
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Robot-assisted laparoscopic radical prostatectomy (RALRP) may be more challenging in obese individuals. This study aimed to evaluate whether obesity had an adverse effect on perioperative outcomes following RALRP.Methods: Hospitalized patients who underwent RAL-RP from 2008-2014 were identified using the National Inpatient Sample database. We grouped RALRP patients into non-obese, obesity class I-II, and obesity class III (morbid obesity). Rates of blood transfusion, intraoperative and postoperative complications, in-hospital mortality, prolonged length of stay, and total costs were compared among the three groups by univariate regression, multivariate regression, and propensity score weighting analysis.Results: Of 53 301 patients identified, 48 725 were non-obese, 3572 were diagnosed with obesity class I-II, and 1004 were diagnosed with morbid obesity. Compared to non-obesity (7.62%), overall postoperative complications were commonly observed in obesity class I-II (10.55%) and morbid obesity (17.11%). Multivariable analyses suggested that morbid obesity was associated with increased overall postoperative (odds ratio PRI 2.00, 95% confidence interval [CI] 1.65-2.42), cardiac (OR 1.63, 95% CI 1.03-2.58), respiratory (OR 4.03, 95% CI 3.04-5.36), genitourinary (OR 1.77, 95% CI 1.08-2.90), miscellaneous medical (OR 1.94, 95% CI 1.58-2.39) complications, prolonged hospitalization (OR 1.86, 95% CI 1.57-2.21), arid 12% higher total cost. Propensity score weighting analysis yielded similar results. Adequate covariate balance was achieved for all variables after weighting.Conclusions: Morbid obesity is adversely associated with perioperative outcomes in RALRP Close management is required in patients undergoing RALRP with morbid obesity for potential worse prognosis.
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