| 1. |
- Ahl, Rebecka, 1987-, et al.
(författare)
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Effects of beta-blocker therapy on mortality after elective colon cancer surgery : a Swedish nationwide cohort study
- 2020
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Colon cancer surgery remains associated with substantial postoperative morbidity and mortality despite advances in surgical techniques and care. The trauma of surgery triggers adrenergic hyperactivation which drives adverse stress responses. We hypothesised that outcome benefits are gained by reducing the effects of hyperadrenergic activity with beta-blocker therapy in patients undergoing colon cancer surgery. This study aims to test this hypothesis.DESIGN: Retrospective cohort study.SETTING AND PARTICIPANTS: This is a nationwide study which includes all adult patients undergoing elective colon cancer surgery in Sweden over 10 years. Patient data were collected from the Swedish Colorectal Cancer Registry. The national drugs registry was used to obtain information about beta-blocker use. Patients were subdivided into exposed and unexposed groups. The association between beta-blockade, short-term and long-term mortality was evaluated using Poisson regression, Kaplan-Meier curves and Cox regression.PRIMARY AND SECONDARY OUTCOMES: Primary outcome of interest was 1-year all-cause mortality. Secondary outcomes included 90-day all-cause and 5-year cancer-specific mortality.RESULTS: The study included 22 337 patients of whom 36.1% were prescribed preoperative beta-blockers. Survival was higher in patients on beta-blockers up to 1 year after surgery despite this group being significantly older and of higher comorbidity. Regression analysis demonstrated significant reductions in 90-day deaths (IRR 0.29, 95% CI 0.24 to 0.35, p<0.001) and a 43% risk reduction in 1-year all-cause mortality (adjusted HR 0.57, 95% CI 0.52 to 0.63, p<0.001) in beta-blocked patients. In addition, cancer-specific mortality up to 5 years after surgery was reduced in beta-blocked patients (adjusted HR 0.80, 95% CI 0.73 to 0.88, p<0.001).CONCLUSION: Preoperative beta-blockade is associated with significant reductions in postoperative short-term and long-term mortality following elective colon cancer surgery. Its potential prophylactic effect warrants further interventional studies to determine whether beta-blockade can be used as a way of improving outcomes for this patient group.
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| 2. |
- Aktypis, Charalampos, et al.
(författare)
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Cardiovascular Toxicities Secondary to Biotherapy and Molecular Targeted Therapies in Neuroendocrine Neoplasms : A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials.
- 2021
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 13:9
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Forskningsöversikt (refereegranskat)abstract
- A broad spectrum of novel targeted therapies with prime antitumor activity and/or ample control of hormonal symptoms together with an overall acceptable safety profile have emerged for patients with metastatic neuroendocrine neoplasms (NENs). In this systematic review and quantitative meta-analysis, the PubMed, EMBASE, Cochrane Central Register of Controlled Trials and clinicaltrials.gov databases were searched to assess and compare the safety profile of NEN treatments with special focus on the cardiovascular adverse effects of biotherapy and molecular targeted therapies (MTTs). Quality/risk of bias were assessed using GRADE criteria. Placebo-controlled randomized clinical trials (RCTs) in patients with metastatic NENs, including medullary thyroid cancer (MTC) were included. A total of 3695 articles and 122 clinical trials registered in clinicaltrials.gov were screened. We included sixteen relevant RCTs comprising 3408 unique patients assigned to different treatments compared with placebo. All the included studies had a low risk of bias. We identified four drug therapies for NENs with eligible placebo-controlled RCTs: somatostatin analogs (SSAs), tryptophan hydroxylase (TPH) inhibitors, mTOR inhibitors and tyrosine kinase inhibitors (TKI). Grade 3 and 4 adverse effects (AE) were more often encountered in patients treated with mTOR inhibitors and TKI (odds ratio [OR]: 2.42, 95% CI: 1.87-3.12 and OR: 3.41, 95% CI: 1.46-7.96, respectively) as compared to SSAs (OR:0.77, 95% CI: 0.47-1.27) and TPH inhibitors (OR:0.77, 95% CI: 0.35-1.69). MTOR inhibitors had the highest risk for serious cardiac AE (OR:3.28, 95% CI: 1.66-6.48) followed by TKIs (OR:1.51, 95% CI: 0.59-3.83). Serious vascular AE were more often encountered in NEN patients treated with mTOR inhibitors (OR: 1.72, 95% CI: 0.64-4.64) and TKIs (OR:1.64, 95% CI: 0.35-7.78). Finally, patients on TKIs were at higher risk for new-onset or exacerbation of pre-existing hypertension (OR:3.31, 95% CI: 1.87-5.86). In conclusion, SSAs and TPH inhibitors appear to be safer as compared to mTOR inhibitors and TKIs with regards to their overall toxicity profile, and cardiovascular toxicities in particular. Special consideration should be given to a patient-tailored approach with anticipated toxicities of targeted NEN treatments together with assessment of cardiovascular comorbidities, assisting clinicians in treatment selection and early recognition/management of cardiovascular toxicities. This approach could improve patient compliance and preserve cardiovascular health and overall quality of life.
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| 3. |
- Alevroudis, Emmanouil, et al.
(författare)
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Clinical utility of 18f-fdg pet in neuroendocrine tumors prior to peptide receptor radionuclide therapy : A Systematic Review and Meta-Analysis
- 2021
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 13:8
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Forskningsöversikt (refereegranskat)abstract
- The role of 18F-FDG PET in patients with variable grades of neuroendocrine tumors (NETs) prior to peptide receptor radionuclide therapy (PRRT) has not been adequately elucidated. We aimed to evaluate the impact of 18F-FDG PET status on disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) in neuroendocrine tumor (NET) patients receiving PRRT. We searched the MEDLINE, Embase, Cochrane Library, and Web of Science databases up to July 2020 and used the Newcastle-Ottawa scale (NOS) criteria to assess quality/risk of bias. A total of 5091 articles were screened. In 12 studies, 1492 unique patients with NETs of different origins were included. The DCR for patients with negative 18F-FDG PET status prior to PRRT initiation was 91.9%, compared to 74.2% in patients with positive 18F-FDG PET status (random effects odds ratio (OR): 4.85; 95% CI: 2.27–10.36). Adjusted analysis of pooled hazard ratios (HRs) confirmed longer PFS and OS in NET patients receiving PRRT with negative 18F-FDG PET (random effects HR:2.45; 95%CIs: 1.48–4.04 and HR:2.25; 95% CIs:1.55–3.28, respectively). In conclusion, 18F-FDG PET imaging prior to PRRT administration appears to be a useful tool in NET patients to predict tumor response and survival outcomes and a negative FDG uptake of the tumor is associated with prolonged PFS and OS.
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| 4. |
- Ali, Fathalla, 1963-, et al.
(författare)
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Peritoneal bridging versus fascial closure in laparoscopic intraperitoneal onlay ventral hernia mesh repair : a randomized clinical trial
- 2020
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Ingår i: BJS Open. - : John Wiley & Sons. - 2474-9842. ; 4:4, s. 587-592
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Many patients develop seroma after laparoscopic ventral hernia repair. It was hypothesized that leaving the hernial sac in situ may cause this complication.METHODS: In this patient- and outcome assessor-blinded, parallel-design single-centre trial, patients undergoing laparoscopic intraperitoneal onlay mesh ventral hernia repair were randomized (1 : 1) to either conventional fascial closure or peritoneal bridging. The primary endpoint was the incidence of seroma 12 months after index surgery detected by CT, evaluated in an intention-to-treat analysis.RESULTS: Between September 2017 and May 2018, 62 patients were assessed for eligibility, of whom 25 were randomized to conventional closure and 25 to peritoneal bridging. At 3 months, one patient was lost to follow-up in the conventional and peritoneal bridging groups respectively. No seroma was detected at 6 or 12 months in either group. The prevalence of clinical seroma was four of 25 (16 (95 per cent c.i. 2 to 30) per cent) versus none of 25 patients in the conventional fascial closure and peritoneal bridging groups respectively at 1 month after surgery (P = 0·110), and two of 24 (8 (0 to 19) per cent) versus none of 25 at 3 months (P = 0·235). There were no significant differences between the groups in other postoperative complications (one of 25 versus 0 of 25), rate of recurrent hernia within 1 year (none in either group) or postoperative pain.CONCLUSION: Conventional fascial closure and peritoneal bridging did not differ with regard to seroma formation after laparoscopic ventral hernia repair.TRIAL REGISTRATION: ClinicalTrials.gov (NCT03344575).
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| 5. |
- Cuni-Sanchez, Aida, et al.
(författare)
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High aboveground carbon stock of African tropical montane forests
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 596:7873, s. 536-542
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Tidskriftsartikel (refereegranskat)abstract
- Tropical forests store 40–50per cent of terrestrial vegetation carbon. However, spatial variations in aboveground live tree biomass carbon (AGC) stocks remain poorly understood, in particular in tropical montane forests. Owing to climatic and soil changes with increasing elevation, AGC stocks are lower in tropical montane forests compared with lowland forests. Here we assemble and analyse a dataset of structurally intact old-growth forests (AfriMont) spanning 44 montane sites in 12 African countries. We find that montane sites in the AfriMont plot network have a mean AGC stock of 149.4megagrams of carbon per hectare (95% confidence interval 137.1–164.2), which is comparable to lowland forests in the African Tropical Rainforest Observation Network4 and about 70per cent and 32per cent higher than averages from plot networks in montane and lowland forests in the Neotropics, respectively. Notably, our results are two-thirds higher than the Intergovernmental Panel on Climate Change default values for these forests in Africa8. We find that the low stem density and high abundance of large trees of African lowland forests is mirrored in the montane forests sampled. This carbon store is endangered: we estimate that 0.8 million hectares of old-growth African montane forest have been lost since 2000. We provide country-specific montane forest AGC stock estimates modelled from our plot network to helpto guide forest conservation and reforestation interventions. Our findings highlight the need for conserving these biodiverse and carbon-rich ecosystems.
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| 6. |
- Dusenge, Mirindi Eric, 1986, et al.
(författare)
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Limited thermal acclimation of photosynthesis in tropical montane tree species
- 2021
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 27:19, s. 4860-4878
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Tidskriftsartikel (refereegranskat)abstract
- The temperature sensitivity of physiological processes and growth of tropical trees remains a key uncertainty in predicting how tropical forests will adjust to future climates. In particular, our knowledge regarding warming responses of photosynthesis, and its underlying biochemical mechanisms, is very limited. We grew seedlings of two tropical montane rainforest tree species, the early-successional species Harungana montana and the late-successional species Syzygium guineense, at three different sites along an elevation gradient, differing by 6.8℃ in daytime ambient air temperature. Their physiological and growth performance was investigated at each site. The optimum temperature of net photosynthesis (ToptA) did not significantly increase in warm-grown trees in either species. Similarly, the thermal optima (ToptV and ToptJ) and activation energies (EaV and EaJ) of maximum Rubisco carboxylation capacity (Vcmax) and maximum electron transport rate (Jmax) were largely unaffected by warming. However, Vcmax, Jmax and foliar dark respiration (Rd) at 25℃ were significantly reduced by warming in both species, and this decline was partly associated with concomitant reduction in total leaf nitrogen content. The ratio of Jmax/Vcmax decreased with increasing leaf temperature for both species, but the ratio at 25℃ was constant across sites. Furthermore, in H. montana, stomatal conductance at 25℃ remained constant across the different temperature treatments, while in S. guineense it increased with warming. Total dry biomass increased with warming in H. montana but remained constant in S. guineense. The biomass allocated to roots, stem and leaves was not affected by warming in H. montana, whereas the biomass allocated to roots significantly increased in S. guineense. Overall, our findings show that in these two tropical montane rainforest tree species, the capacity to acclimate the thermal optimum of photosynthesis is limited while warming-induced reductions in respiration and photosynthetic capacity rates are tightly coupled and linked to responses of leaf nitrogen.
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| 7. |
- Inabnet, William B., 3rd, et al.
(författare)
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Correlating the Bethesda System for Reporting Thyroid Cytopathology with Histology and Extent of Surgery : A Review of 21,746 Patients from Four Endocrine Surgery Registries Across Two Continents
- 2020
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Ingår i: World Journal of Surgery. - : Springer. - 0364-2313 .- 1432-2323. ; 44:2, s. 426-435
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Bethesda system for cytopathology (TBSRTC) is a 6-tier diagnostic framework developed to standardize thyroid cytopathology reporting. The aim of this study was to determine the risk of malignancy (ROM) for each Bethesda category.METHODS: Thyroidectomy-related data from 314 facilities in 22 countries were entered into the following outcome registries: CESQIP (North America), Eurocrine (Europe), SQRTPA (Sweden) and UKRETS (UK). Demographic, cytological, pathologic and extent of surgery data were mapped into one dataset and analyzed.RESULTS: Out of 41,294 thyroidectomy patient entries from January 1, 2015, to June 30, 2017, 21,746 patients underwent both thyroid FNA and surgery. A comparison of cytology and surgical pathology data demonstrated a ROM for Bethesda categories 1 to 6 of 19.2%, 12.7%, 31.9%, 31.4%, 77.8% and 96.0%, respectively. Male patients had a higher rate of malignancy for every Bethesda category. Secondary analysis demonstrated a high ROM in male patients with Bethesda 3 category aged 31-35 years (52.1%, 95% confidence interval (CI) 37.9-66.2%), aged 36-40 years (55.9%, 95% CI 39.2-72.6%) and aged 41-45 years (46.9%, 95% CI 33-60.9%). Patients with Bethesda 5 and 6 scores were more likely to undergo total thyroidectomy (65.9% and 84.6%); for patients with Bethesda scores 2 and 3, a higher percentage of females underwent total thyroidectomy compared to males in spite of a higher ROM for males.CONCLUSIONS: These data demonstrate that Bethesda categories 1-4 are associated with a higher ROM compared to the first edition of TBSRTC, especially in male patients, and validate findings from the second edition of TBSRTC.
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| 8. |
- Kjellman, M., et al.
(författare)
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A Plasma Protein Biomarker Strategy for Detection of Small Intestinal Neuroendocrine Tumors
- 2021
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Ingår i: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 111:9, s. 840-849
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Tidskriftsartikel (refereegranskat)abstract
- Background: Small intestinal neuroendocrine tumors (SI-NETs) are difficult to diagnose in the early stage of disease. Current blood biomarkers such as chromogranin A (CgA) and 5-hydroxyindolacetic acid have low sensitivity (SEN) and specificity (SPE). This is a first preplanned interim analysis (Nordic non-interventional, prospective, exploratory, EXPLAIN study [NCT02630654]). Its objective is to investigate if a plasma protein multi-biomarker strategy can improve diagnostic accuracy (ACC) in SI-NETs. Methods: At the time of diagnosis, before any disease-specific treatment was initiated, blood was collected from patients with advanced SI-NETs and 92 putative cancer-related plasma proteins from 135 patients were analyzed and compared with the results of age- and sex-matched controls (n = 143), using multiplex proximity extension assay and machine learning techniques. Results: Using a random forest model including 12 top ranked plasma proteins in patients with SI-NETs, the multi-biomarker strategy showed SEN and SPE of 89 and 91%, respectively, with negative predictive value (NPV) and positive predictive value (PPV) of 90 and 91%, respectively, to identify patients with regional or metastatic disease with an area under the receiver operator characteristic curve (AUROC) of 99%. In 30 patients with normal CgA concentrations, the model provided a diagnostic SPE of 98%, SEN of 56%, and NPV 90%, PPV of 90%, and AUROC 97%, regardless of proton pump inhibitor intake. Conclusion: This interim analysis demonstrates that a multi-biomarker/machine learning strategy improves diagnostic ACC of patients with SI-NET at the time of diagnosis, especially in patients with normal CgA levels. The results indicate that this multi-biomarker strategy can be useful for early detection of SI-NETs at presentation and conceivably detect recurrence after radical primary resection.
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| 9. |
- Koumarianou, Anna, et al.
(författare)
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Pathogenesis and Clinical Management of Mesenteric Fibrosis in Small Intestinal Neuroendocine Neoplasms : A Systematic Review
- 2020
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 9:6
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Forskningsöversikt (refereegranskat)abstract
- Mesenteric fibrosis (MF) constitutes an underrecognized sequela in patients with small intestinal neuroendocrine neoplasms (SI-NENs), often complicating the disease clinical course. The aim of the present systematic review, carried out by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology, is to provide an update in evolving aspects of MF pathogenesis and its clinical management in SI-NENs. Complex and dynamic interactions are present in the microenvironment of tumor deposits in the mesentery. Serotonin, as well as the signaling pathways of certain growth factors play a pivotal, yet not fully elucidated role in the pathogenesis of MF. Clinically, MF often results in significant morbidity by causing either acute complications, such as intestinal obstruction and/or acute ischemia or more chronic conditions involving abdominal pain, venous stasis, malabsorption and malnutrition. Surgical resection in patients with locoregional disease only or symptomatic distant stage disease, as well as palliative minimally invasive interventions in advanced inoperable cases seem clinically meaningful, whereas currently available systemic and/or targeted treatments do not unequivocally affect the development of MF in SI-NENs. Increased awareness and improved understanding of the molecular pathogenesis of MF in SI-NENs may provide better diagnostic and predictive tools for its timely recognition and intervention and also facilitates the development of agents targeting MF.
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| 10. |
- Mauri, Giovanni, et al.
(författare)
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European Thyroid Association and Cardiovascular and Interventional Radiological Society of Europe 2021 Clinical Practice Guideline for the Use of Minimally Invasive Treatments in Malignant Thyroid Lesions
- 2021
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Ingår i: European thyroid journal. - : S. Karger. - 2235-0640 .- 2235-0802. ; 10:3, s. 185-197
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Tidskriftsartikel (refereegranskat)abstract
- The growing detection of papillary thyroid microcarcinomas (PTMCs) is paralleled by an increase in surgical procedures. Due to the frequent indolent nature, cost, and risk of surgery, active surveillance (AS) and ultrasound-guided minimally invasive treatments (MITs) are in suitable cases of incidental PTMC proposed as alternatives to thyroidectomy. Surgery and radioiodine are the established treatments for relapsing cervical differentiated thyroid carcinoma (DTC) metastases. But radioiodine refractoriness, risk of surgical complications, adverse influence on quality of life, or declining repeat surgery have led to AS and MIT being considered as alternatives for slow-growing DTC nodal metastases. Also, for distant radioiodine-refractory metastases not amenable to surgery, MIT is proposed as part of a multimodality therapeutic approach. The European Thyroid Association and the Cardiovascular and Interventional Radiological Society of Europe commissioned these guidelines for the appropriate use of MIT. Based on a systematic PubMed search, an evidence-based approach was applied, and both knowledge and practical experience of the panelists were incorporated to develop the manuscript and the specific recommendations. We recommend that when weighing between surgery, radioiodine, AS, or MIT for DTC, a multidisciplinary team including members with expertise in interventional radiology assess the demographic, clinical, histological, and imaging characteristics for appropriate selection of patients eligible for MIT. Consider TA in low-risk PTMC patients who are at surgical risk, have short life expectancy, relevant comorbidities, or are unwilling to undergo surgery or AS. As laser ablation, radiofrequency ablation, and microwave ablation are similarly safe and effective thermal ablation (TA) techniques, the choice should be based on the specific competences and resources of the centers. Use of ethanol ablation and high-intensity focused ultrasound is not recommended for PTMC treatment. Consider MIT as an alternative to surgical neck dissection in patients with radioiodine refractory cervical recurrences who are at surgical risk or decline further surgery. Factors that favor MIT are previous neck dissection, presence of surgical complications, small size metastases, and <4 involved latero-cervical lymph nodes. Consider TA among treatment options in patients with unresectable oligometastatic or oligoprogressive distant metastases to achieve local tumor control or pain palliation. Consider TA, in combination with bone consolidation and external beam radiation therapy, as a treatment option for painful bone metastases not amenable to other established treatments.
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