| 1. |
- Ahl, Rebecka, 1987-
(författare)
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The Association Between Beta-Blockade and Clinical Outcomes in the Context of Surgical and Traumatic Stress
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Traumatic injury and major abdominal surgery are areas in general surgery associated with high rates of morbidity and mortality. The overall colorectal cancer surgery mortality rate is around 4%, with that for emergency surgery more than twice as high as for planned. Surgical morbidity varies between 25% and 45%. Around half of trauma patients develop low mood. In one quarter of patients this becomes permanent. Depression is known to impede physical rehabilitation and recovery. The onset of physiological stress, driven by adrenergic hyperactivity following traumatic and surgical injury is hypothesized to contribute to these adverse outcomes. Interest has therefore been sparked into blocking adrenergic receptor activation.Papers I and II investigated the role of beta-blocker therapy in preventing post-traumatic depression following severe traumatic brain injury (Paper I) and severe extracranial injury (Paper II). The Karolinska University Hospital Trauma Registry was used to identify patients admitted between 2007 and 2011. In Paper I (n = 545), patients on pre-injury beta-blocker therapy were matched to beta-blocker naïve patients with equivalent injury burden. Results revealed that beta-blocked patients exhibited a 60% reduced risk of needing antidepressant therapy within one year of trauma. In Paper II (n = 596), the lack of beta-blocker use before extracranial trauma was linked to a three-fold increase in the risk of antidepressant initiation.Papers III-V explored the role of pre-operative beta-blocker therapy in patients undergoing surgery for colorectal cancer between 2007 and 2016, identified using the nationwide Swedish Colorectal Cancer Registry. Paper III (n = 3,187) identified a 69% reduction in the risk of 30-day mortality in beta-blocked patients. Paper IV (n = 22,337) outlined long-term survival benefits for patients on beta-blocker therapy prior to undergoing elective surgery for colon cancer. Beta-blocked patients showed a risk reduction of 42% for 1-year all-cause mortality and 18% for 5-year cancerspecific mortality. Similarly, patients on beta-blocker therapy who underwent surgery for rectal cancer demonstrated improved survival up to one year after surgery with a risk reduction of 57% and a reduction in anastomotic failure and infectious complications in Paper V (n = 11,966).
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| 2. |
- Baban, Bayar, 1973-
(författare)
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Colorectal cancer and surgery : Insights into insulin resistance and inflammatory markers
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The art of surgery has progressively extended from the realm of anatomy to encompass physiology and beyond, in search of further refinement and optimal recovery. Integral to this is a deeper understanding of the body’s essential metabolic and inflammatory responses to surgical trauma.This thesis aims to provide insights into the intricate interplay between insulin resistance, inflammation and surgical interventions in colorectal cancer patients, as each has an influence on postoperative recovery. Particular emphasis is placed on the role of inflammasomes – central mediators of the innate immune response, adept at detecting and responding to a diverse range of triggers, yet insufficiently explored in these specific contexts.Study I is a comparative analysis of the hyperinsulinemic–euglycaemic clamp and homeostatic model assessment (HOMA) in determining postoperative insulin resistance in 113 patients undergoing various elective surgeries. The findings establish the clamp as the accurate method, detecting key physiological distinctions missed by HOMA.Study II, an exploratory case–control study, assesses insulin sensitivity and inflammatory markers in 20 colorectal cancer patients compared to 10 matched healthy controls. Results indicate insulin resistance, reduced inflammasome activity in circulating immune cells and elevated systemic IL-1β and IL-6 levels in patients.Study III, a pilot exploratory study of 17 patients from Study II, assesses the impact of surgical technique, open versus minimally invasive surgery, on postoperative insulin resistance and inflammation in colorectal cancer resections. It indicates a differential inflammatory response with higher levels in open surgeries, yet a consistent degree of insulin resistance across both surgical techniques.Study IV explores the perioperative temporal sequencing of inflammation and inflammasome action in 18 patients from Study II undergoing elective colorectal cancer resections. It points to a more immediate and pronounced inflammatory response in open surgery compared to minimally invasive surgery, though both techniques show reduced intraoperative caspase-1 activity.In conclusion, the hyperinsulinemic euglycaemic clamp is the accurate method in determinations of postoperative insulin resistance. Patients with colorectal cancer, in comparison to matched healthy controls, exhibit insulin resistance and higher levels of inflammation, but decreased inflammasome (caspase-1) activity in circulating immune cells. Finally, colorectal cancer resections induce both insulin resistance and inflammation; however, the surgical technique utilized only significantly affects the latter, with generally higher inflammatory / inflammasome responses in open surgery.
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| 3. |
- Engelheart, Stina, 1976-
(författare)
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Nutritional status in a functional perspective : A study in a cohort of older people in home health care
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- High age is a risk factor for most acute and chronic diseases, injuries and function disabilities, and hence, an important risk factor for nutritional problems. A great deal of elderly health care in Sweden are performed in the patient’s home environment and home health care has been transformed to more advanced medical care the last decades.The aim of this thesis was to comprehensively describe the nutritional status and its change over time in a population of older people receiving home health care. The aim includes to propose a framework for investigating and analysing the nutritional status in older people.Nutritional status was studied at enrolment in home health care and regularly followed up for three years. Patients that were 65 years or older and needed home health care for at least three months between 2012 and 2017 were asked to join the study, resulting in 69 participants (64%women).Data collection and analysis of the nutritional status was based on the proposed model for assessing the nutritional status in a comprehensive functional perspective (paper 1). The model comprises four domains that affect the nutritional status and functional outcome in a bidirectional way. In paper 2 we concluded that malnutrition, sarcopenia, frailty and dehydration are highly prevalent in the population and the most important indicators were loss of appetite and dehydration. This was confirmed in paper 3, were nutritional status was analysed with a statistical approach. A total of 103 indicators of nutritional status were reduced to 19 that were suggested to be primary investigated. Also, the paper empirically confirmed the relationship within as well as between the domains suggested in paper 1. Finally, we studied meal pattern, being a part of one of the domains (paper 4). We found indications that presence of at least one large meal (high energy intake) per day had more impact on the total daily energy and protein intake than more eating occasions during the day.
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| 4. |
- Wijk, Lena, 1971-
(författare)
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Enhanced Recovery After Hysterectomy
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Objectives: To study recovery after hysterectomy under Enhanced Recovery After Surgery (ERAS) care, and in relation to different operation techniques.Materials and Methods: An observational study was conducted comparing 85 patients undergoing hysterectomy with ERAS care to 120 patients immediately before establishing ERAS. In a prospective cohort study of 121 consecutive patients undergoing hysterectomy, the outcome was compared for patients with malignant versus benign indications. The main outcome measure was length of stay (LOS). A randomised controlled trial (RCT) of 20 women scheduled for hysterectomy compared robot-assisted laparoscopic with abdominal hysterectomy in terms of the development of insulin resistance, inflammatory reactions, and clinical recovery, and examined the relation to hormonal status. All studies were conducted in 2011--2015, at the Department of Obstetrics and Gynaecology, Örebro University Hospital, Sweden.Results: Implementation of a structured ERAS protocol significantly reduced LOS compared to non-ERAS care. The effect was similar between patients with malignant and benign indications for surgery. No difference in complications was found. There was no difference in development of insulin resistance between robotic and abdominal technique, but clinical outcomes and inflammatory responses significantly favoured robot-assisted hysterectomy. Female sex hormone status was associated with the development of insulin resistance.Conclusions: Recovery after hysterectomy can be influenced. ERAS care seems to be effective and safe. Clinical outcome can also be influenced by operational technique. Hysterectomy triggers a stress reaction in both the metabolic and the inflammatory system. It remains unclear why the reduced inflammatory reaction and favourable clinical outcome in robotic surgery were not mirrored by less insulin resistance. This could not be explained by female sex hormone status.
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| 5. |
- Ah, Rebecka, et al.
(författare)
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Prognostic Value of P-POSSUM and Osteopenia for Predicting Mortality After Emergency Laparotomy in Geriatric Patients
- 2019
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Ingår i: Bulletin of emergency and trauma. - : Shiraz University of Medical Sciences. - 2322-2522 .- 2322-3960. ; 7:3, s. 223-231
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate the Portsmouth-Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (P-POSSUM) in comparison with other risk factors for mortality including osteopenia as an indicator for frailty in geriatric patients subjected to emergency laparotomy.Methods: All geriatric patients (≥65 years) undergoing emergency laparotomy at a single university hospital between 1/2015 and 12/2016 were included in this cohort study. Demographics and outcomes were retrospectively collected from medical records. Association between prognostic markers and 30-day mortality was assessed using Poisson and backward stepwise regression models. Prognostic value was assessed using receiver operating characteristic (ROC) curves.Results: =0.004) while osteopenia was not. P-POSSUM had poor prognostic value for 30-day mortality with an area under the ROC curve (AUC) of 0.59. The prognostic value of P-POSSUM improved significantly when adjusting for patient covariates (AUC=0.83).Conclusion: P-POSSUM and osteopenia alone hardly predict 30-day mortality in geriatric patients following emergency laparotomy. P-POSSUM adjusted for other patient covariates improves the prediction.
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| 6. |
- Ahl, Rebecka, 1987-, et al.
(författare)
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Effect of beta-blocker therapy on early mortality after emergency colonic cancer surgery
- 2019
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Ingår i: British Journal of Surgery. - : John Wiley & Sons. - 0007-1323 .- 1365-2168. ; 106:4, s. 477-483
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Emergency colorectal cancer surgery is associated with significant mortality. Induced adrenergic hyperactivity is thought to be an important contributor. Downregulating the effects of circulating catecholamines may reduce the risk of adverse outcomes. This study assessed whether regular preoperative beta-blockade reduced mortality after emergency colonic cancer surgery.METHODS: This cohort study used the prospectively collected Swedish Colorectal Cancer Registry to recruit all adult patients requiring emergency colonic cancer surgery between 2011 and 2016. Patients were subdivided into those receiving regular beta-blocker therapy before surgery and those who were not (control). Demographics and clinical outcomes were compared. Risk factors for 30-day mortality were evaluated using Poisson regression analysis.RESULTS: A total of 3187 patients were included, of whom 685 (21·5 per cent) used regular beta-blocker therapy before surgery. The overall 30-day mortality rate was significantly reduced in the beta-blocker group compared with controls: 3·1 (95 per cent c.i. 1·9 to 4·7) versus 8·6 (7·6 to 9·8) per cent respectively (P < 0·001). Beta-blocker therapy was the only modifiable protective factor identified in multivariable analysis of 30-day all-cause mortality (incidence rate ratio 0·31, 95 per cent c.i. 0·20 to 0·47; P < 0·001) and was associated with a significant reduction in death of cardiovascular, respiratory, sepsis and multiple organ failure origin.CONCLUSION: Preoperative beta-blocker therapy may be associated with a reduction in 30-day mortality following emergency colonic cancer surgery.
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| 7. |
- 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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| 8. |
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| 9. |
- Ahl, Rebecka, 1987-, et al.
(författare)
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The Relationship Between Severe Complications, Beta-Blocker Therapy and Long-Term Survival Following Emergency Surgery for Colon Cancer
- 2019
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Ingår i: World Journal of Surgery. - : Springer. - 0364-2313 .- 1432-2323. ; 43:10, s. 2527-2535
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Emergency surgery for colon cancer carries significant morbidity, and studies show more than doubled mortality when comparing elective to emergency surgery. The relationship between postoperative complications and survival has been outlined. Beta-blocker therapy has been linked to improved postoperative outcomes. This study aims to assess the impact of postoperative complications on long-term survival following emergency surgery for colon cancer and to determine whether beta-blockade can reduce complications.STUDY DESIGN: This cohort study utilized the prospective Swedish Colorectal Cancer Registry to identify adults undergoing emergency colon cancer surgery between 2011 and 2016. Prescription data for preoperative beta-blocker therapy were collected from the national drug registry. Cox regression was used to evaluate the effect of beta-blocker exposure and complications on 1-year mortality, and Poisson regression was used to evaluate beta-blocker exposure in patients with major complications.RESULTS: A total of 3139 patients were included with a mean age of 73.1 [12.4] of which 671 (21.4%) were prescribed beta-blockers prior to surgery. Major complications occurred in 375 (11.9%) patients. Those suffering major complications showed a threefold increase in 1-year mortality (adjusted HR = 3.29; 95% CI 2.75-3.94; p < 0.001). Beta-blocker use was linked to a 60% risk reduction in 1-year mortality (adjusted HR = 0.40; 95% CI 0.26-0.62; p < 0.001) but did not show a statistically significant association with reductions in major complications (adjusted IRR = 0.77; 95% CI 0.59-1.00; p = 0.055).CONCLUSION: The development of major complications after emergency colon cancer surgery is associated with increased mortality during one year after surgery. Beta-blocker therapy may protect against postoperative complications.
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| 10. |
- Ahl, Rebecka, 1987-, et al.
(författare)
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β-Blockade in Rectal Cancer Surgery : A Simple Measure of Improving Outcomes
- 2020
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Ingår i: Annals of Surgery. - : Lippincott Williams & Wilkins. - 0003-4932 .- 1528-1140. ; 271:1, s. 140-146
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To ascertain whether regular β-blocker exposure can improve short- and long-term outcomes after rectal cancer surgery.BACKGROUND: Surgery for rectal cancer is associated with substantial morbidity and mortality. There is increasing evidence to suggest that there is a survival benefit in patients exposed to β-blockers undergoing non-cardiac surgery. Studies investigating the effects on outcomes in patients subjected to surgery for rectal cancer are lacking.METHODS: All adult patients undergoing elective abdominal resection for rectal cancer over a 10-year period were recruited from the prospectively collected Swedish Colorectal Cancer Registry. Patients were subdivided according to preoperative β-blocker exposure status. Outcomes of interest were 30-day complications, 30-day cause-specific mortality, and 1-year all-cause mortality. The association between β-blocker use and outcomes were analyzed using Poisson regression model with robust standard errors for 30-day complications and cause-specific mortality. One-year survival was assessed using Cox proportional hazards regression model.RESULTS: A total of 11,966 patients were included in the current study, of whom 3513 (29.36%) were exposed to regular preoperative β-blockers. A significant decrease in 30-day mortality was detected (incidence rate ratio = 0.06, 95% confidence interval: 0.03-0.13, P < 0.001). Deaths of cardiovascular nature, respiratory origin, sepsis, and multiorgan failure were significantly lower in β-blocker users, as were the incidences in postoperative infection and anastomotic failure. The β-blocker positive group had significantly better survival up to 1 year postoperatively with a risk reduction of 57% (hazard ratio = 0.43, 95% confidence interval: 0.37-0.52, P < 0.001).CONCLUSIONS: Preoperative β-blocker use is strongly associated with improved survival and morbidity after abdominal resection for rectal cancer.
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