Antithrombotic Treatment and Clinical Outcomes After Intracerebral Hemorrhage: A Retrospective Cohort Study from the Swedish Stroke Register.

BACKGROUND: A rapid shift has occurred from vitamin K antagonists toward direct oral anticoagulants, which have a lower risk of intracerebral hemorrhage (ICH). However, effects on clinical outcomes after ICH are understudied. We aimed to describe the prevalence of antithrombotic drugs and to study the prognosis among prestroke functionally independent Swedish patients with ICH. METHODS AND RESULTS: We identified all patients diagnosed with nontraumatic ICH in 2017 to 2021 from the Swedish Stroke Register (n=13 155) and assessed death and functional outcome at 3 months after ICH in prestroke functionally independent patients (n=10 014). Functional outcome was estimated among 3-month survivors on the basis of self-reported activities of daily living scores. Risks of outcomes were estimated using Poisson regression. In 13 155 patients, 14.5% used direct oral anticoagulant, 10.1% vitamin K antagonists, and 21.6% antiplatelets at ICH onset. Among 10 014 pre-stroke activities of daily living-independent patients, oral anticoagulants and antiplatelets were associated with increased mortality risk (adjusted risk ratio, 1.27 [95% CI, 1.13-1.43]; P<0.001; and adjusted risk ratio, 1.23 [95% CI, 1.13-1.34]; P<0.001 respectively). Mortality risk did not statistically differ between antiplatelets and oral anticoagulants nor between direct oral anticoagulant and vitamin K antagonists. Among 5126 patients with nonmissing functional outcome (69.1% of survivors), antiplatelets (adjusted risk ratio, 1.06 [95% CI, 0.99-1.13]; P=0.100) and oral anticoagulants (adjusted risk ratio, 1.01 [95% CI, 0.92-1.12]; P=0.768) were not statistically significantly associated with functional dependence. CONCLUSIONS: There was no statistically significant difference in mortality risk between direct oral anticoagulant and vitamin K antagonists in prestroke functionally independent patients (unadjusted for oral anticoagulant class indication). Furthermore, mortality risk in antiplatelet and oral anticoagulant users might differ less than previously suggested.

Fracture Incidence in Graves' Disease: A Population-Based Study.

Background: Population-based studies have indicated an increase in bone turnover in hyperthyroidism with a subsequent decrease in bone mineral density and an increased risk of fractures, especially in postmenopausal women. However, heterogeneity between studies prevents a definitive conclusion. Graves' disease (GD) is an autoimmune disease, and it is the most common cause of hyperthyroidism. The aim of this study was to investigate fracture risk in patients with GD. Methods: A total of 2134 patients with incident GD and 21,261 age, sex- and county-matched controls were included 16-18 years after diagnosis in a retrospective cohort study. Drug and patient national registries in Sweden were used to assess the risk of developing skeletal complications. Up to 10 years of age, sex- and county-matched controls per patient were selected from databases from the National Board of Health and Welfare and Statistics Sweden. Cox proportional hazards models were fitted to estimate hazard ratios (HR) and confidence intervals [CI]. Results: There were no significant differences in fracture rates between GD and controls but after adjustment for comorbidities, the data showed higher vertebral fracture rates in male GD patients aged >52 years compared to male controls, HR = 2.83 [CI 1.05-7.64]. The rates of osteoporosis treatments as well as treatment with corticosteroids were higher in patients with GD. However, HR for the association between GD and fractures remained largely unchanged after adjustment for osteoporosis treatments and treatments with corticosteroids. Conclusions: There were no significant differences in total fracture rate between GD and the general population. However, men older than 52 years had a higher vertebral fracture rate. This study also shows that patients with treated GD receive more osteoporosis treatments compared to the general population.

Androgen deprivation therapy in men with prostate cancer is not associated with COVID-2019 infection.

BACKGROUND: Androgens may play a role in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and host responses as the virus is dependent on the androgen-regulated protein transmembrane serine protease 2 for cell entry. Studies have indicated that prostate cancer patients receiving androgen deprivation therapy (ADT) are at reduced risk of SARS-CoV-2 infection and serious complications compared with patients without ADT, but data are inconsistent. METHODS: A total of 655 prostate cancer patients who were under surveillance at two urology departments in Sweden on April 1, 2020 were included in the study as well as 240 patients with benign prostatic hyperplasia (BPH). At follow-up early in 2021, the participants completed a questionnaire containing information about symptoms compatible with coronavirus disease 2019 (COVID-19). Blood samples were also collected for the assessment of SARS-CoV-2 IgG antibodies (SARS-CoV-2 Total; Siemens). We used multivariable logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between ADT and the risk of SARS-CoV-2 infection. RESULTS: The cumulative incidence of SARS-CoV-2 seropositivity was 13.4% among patients receiving ADT and 10.4% among patients without ADT. After adjusting for potential confounders, we observed no differences in symptoms or risk of SARS-CoV-2 infection between patients with and without ADT (OR: 0.98; 95% CI: 0.52-1.85). Higher body mass index, Type 1 diabetes, and prostate cancer severity, defined by high Gleason score (8-10; OR: 2.06; 95% CI: 1.04-4.09) or elevated levels of prostate-specific antigen (>20 µg/l; OR: 2.15; 95% CI: 1.13-4.07) were associated with increased risk of SARS-CoV-2 infection. Overall, the risk of SARS-CoV-2 infection was not higher among men with prostate cancer than among men with BPH. CONCLUSIONS: Our results do not support the hypothesis that ADT use in prostate cancer patients reduces the risk or symptom severity of SARS-CoV-2 infection or that prostate cancer patients are at increased risk of COVID-19 compared with men without prostate cancer.

Clinical outcomes and sick leave in relation to UDCA treatment in Swedish patients with primary biliary cholangitis.

OBJECTIVES: Primary biliary cholangitis (PBC) is an autoimmune liver disease that may progress into liver cirrhosis. Ursodeoxycholic acid (UDCA) is known to prevent or delay the disease progression, but little is known about work incapacity in PBC patients. We aimed to compare clinical outcomes (transplantation-free survival; cirrhosis development) and sick leave in patients with PBC with and without UDCA therapy. METHODS: The medical records of 526 patients with PBC diagnosed from 2004 to 2016 were reviewed retrospectively. Sick leave data retrieved from the Swedish Social Insurance Agency were analysed for a sub-cohort of patients and matched controls. Cox regression was used for analysis of clinical outcomes. Logistic and conditional logistic regressions were used for sick leave analysis. RESULTS: A total of 10.6% of patients died and 3.4% received liver transplantation over a median follow-up time of 5.7 years. UDCA-untreated patients (HR 3.62 (95%CI 2.02-6.49)) and UDCA non-responders (HR 3.78 (95% CI 1.87-7.66)) had higher mortality or transplantation rates than UDCA responders. Patients with PBC had higher odds of sick leave (OR 2.50; 95% CI 1.69-3.70) than matched controls. Untreated patients were more likely to be on sick leave (OR 3.22; 95% CI 1.12-9.25) two years after diagnosis than UDCA responders. CONCLUSION: Both untreated patients and UDCA non-responders had lower liver transplantation-free survival rates than UDCA responders. Patients with PBC were more likely to be on sick leave compared to matched controls from the general population.

Beta-blocker use and urothelial bladder cancer survival: a Swedish register-based cohort study.

BACKGROUND: Recent observational studies linked ß-adrenergic receptor blocker use with improved survival in patients with several cancer types, but there is no information on the potential effects of ß-blockers in patients with bladder cancer. Literature from pre-clinical studies is also limited, but urothelial cancer can exhibit significant overexpression of ß-adrenergic receptors relative to normal urothelial tissue, suggesting that urothelial cancer may benefit from ß-blockade therapy. We thus aimed to explore the possible association between ß-blocker use and bladder cancer-specific mortality (BCSM) among patients with urothelial bladder cancer. MATERIAL AND METHODS: Patients diagnosed during 2006-2014 and identified from the Swedish Cancer Register (n = 16,669) were followed until 31 December 2015. Cox regression was used to evaluate the association of ß-blockers dispensed within 90 days prior to cancer diagnosis with BCSM (primary outcome) and all-cause mortality, while controlling for socio-demographic factors, tumor characteristics, comorbidity, other medications and surgical procedures. Hazard ratios (HR) with 95% confidence intervals (CI) were reported. RESULTS: Overall, ß-blocker use was associated with lower BCSM [HR 0.88 (95%CI 0.81-0.96)]. Especially use of nonselective ß-blockers showed a clear inverse association in comparison with both nonuse [0.66 (0.50-0.86)] and use of other antihypertensive medications [0.72 (0.54-0.95)]. The inverse association was most pronounced among patients with locally advanced/metastatic disease: [0.35 (0.18-0.68)]. A lower-magnitude inverse association was observed for selective ß-blocker use [0.91 (0.83-0.99)]. Largely similar inverse associations were observed for hydrophilic [0.82 (0.70-0.95)] and lipophilic [0.91 (0.83-1.00)] ß-blocker use. CONCLUSION: ß-blocker use, particularly of the nonselective type, was associated with lower BCSM, especially in patients with locally advanced/metastatic urothelial bladder cancer.

Mortality in patients with Crohn's disease in Örebro, Sweden 1963-2010.

BACKGROUND: Some studies have suggested a reduced life expectancy in patients with Crohn's disease (CD) compared with the general population. The evidence, however, is inconsistent. AIMS: Prompted by such studies, we studied survival of CD patients in Örebro county, Sweden. METHODS: From the medical records, we identified all patients diagnosed with CD during 1963-2010 with follow-up to the end of 2011. We estimated: overall survival, net and crude probabilities of dying from CD, relative survival ratio (RSR), and excess mortality rate ratios (EMRR) at 10-year follow-up. RESULTS: The study included 492 patients (226 males, 266 females). Median age at diagnosis was 32 years (3-87). Net and crude probabilities of dying from CD increased with increasing age and were higher for women. Net survival of patients aged ≥60 at diagnosis was worse for patients diagnosed during 1963-1985 (54%) than for patients diagnosed during 1986-1999 (88%) or 2000-2010 (93%). Overall, CD patients' survival was comparable to that in the general population [RSR = 0.98; 95% CI: (0.95-1.00)]. However, significantly lower than expected survival was suggested for female patients aged ≥60 diagnosed during the 1963-1985 [RSR = 0.47 (0.07-0.95)]. The adjusted model suggested that, compared with diagnostic period 1963-1985, disease-related excess mortality declined during 2000-2010 [EMRR = 0.36 (0.07-1.96)]; and age ≥60 at diagnosis [EMRR = 7.99 (1.64-39.00), reference: age 40-59], female sex [EMRR = 4.16 (0.62-27.85)], colonic localization [EMRR = 4.20 (0.81-21.88), reference: ileal localization], and stricturing/penetrating disease [EMRR = 2.56 (0.52-12.58), reference: inflammatory disease behaviour] were associated with poorer survival. CONCLUSION: CD-related excess mortality may vary with diagnostic period, age, sex and disease phenotype.Key summaryThere is inconsistent evidence on life expectancy of patients with Crohn's diseaseCrohn's disease-specific survival improved over time.Earlier diagnosis period, older age at diagnosis, female sex, colonic disease and complicated disease behaviour seems to be associated with excess Crohn's disease-related mortality.

Real-world effectiveness of vedolizumab in inflammatory bowel disease: week 52 results from the Swedish prospective multicentre SVEAH study.

BACKGROUND: Prospectively and systematically collected real-world data on vedolizumab are scarce. We aimed to assess the long-term clinical effectiveness of vedolizumab in inflammatory bowel disease (IBD). METHODS: This study was a prospective, observational, multicentre study. Overall, 286 patients with active IBD were included (Crohn's disease, n = 169; ulcerative colitis, n = 117). The primary outcomes were clinical response at week 12 and clinical remission at week 52, based on the Harvey Bradshaw Index and the partial Mayo Clinic score. Secondary outcomes included clinical remission at week 12, clinical response at week 52, corticosteroid-free clinical remission at week 52, changes in biochemical measures, and health-related quality of life (HRQoL). RESULTS: At baseline, 88% of the patients were exposed to anti-TNF and 41% of the patients with Crohn's disease had undergone ⩾1 surgical resection. At week 12, clinical response was 27% and remission 47% in Crohn's disease; corresponding figures in ulcerative colitis were 52% and 34%. Clinical response, remission and corticosteroid-free remission at week 52 were 22%, 41% and 40% in Crohn's disease and 49%, 47% and 46% in ulcerative colitis, respectively. A statistically significant decrease in median faecal-calprotectin and C-reactive protein was observed at 12 and 52 weeks in patients with Crohn's disease and ulcerative colitis. The HRQoL measures Short Health Scale and EuroQol 5-Dimensions improved in both Crohn's disease and ulcerative colitis patients (p < 0.001). Clinical disease activity at baseline was inversely associated with clinical remission at week 52. CONCLUSION: Vedolizumab proved effective for the treatment of refractory IBD in clinical practice.

Validity of Routinely Collected Swedish Data in the International Enhanced Recovery After Surgery (ERAS) Database.

BACKGROUND: This study aims to assess patient coverage, validity and data quality in the Swedish part of the International Enhanced Recovery After Surgery (ERAS) Interactive Audit System (EIAS). METHOD: All Swedish ERAS centers that recorded colorectal surgery data in EIAS between January 1, 2017, and December 31, 2017, were included (N = 12). Information registered in EIAS was compared with data from electronic medical records at each hospital to assess the overall coverage of EIAS. Twenty random-selected patients from each of the contributing centers were assessed for accuracy for a set of clinically relevant variables. All patients admitted to the contributing centers were included for the assessment of rate of missing on a selection of key clinical variables. RESULTS: Eight hospitals provided complete information for the evaluation, while four hospitals only allowed assessment of coverage and missing data. The eight hospitals had an overall coverage of 98.8% in EIAS (n = 1301) and the four 86.7% (n = 811). The average agreement for the assessed postoperative outcome variables was 96.5%. The accuracy was excellent for 'length of hospital stay,' 'reoperation,' and 'any complications,' but lower for other types of complications. Only a few variables had more than 5% missing data, and missingness was associated with hospital type and size. CONCLUSION: This validation of the Swedish part of the international ERAS database suggests high patient coverage in EIAS and high agreement and limited missingness in clinically relevant variables. This validation approach or a modified version can be used for continued validation of the International ERAS database.

Mortality in first- and second-generation immigrants to Sweden diagnosed with type 2 diabetes: a 10 year nationwide cohort study.

AIMS/HYPOTHESIS: Non-Western immigrants to Europe are at high risk for type 2 diabetes. In this nationwide study including incident cases of type 2 diabetes, the aim was to compare all-cause mortality (ACM) and cause-specific mortality (CSM) rates in first- and second-generation immigrants with native Swedes. METHODS: People living in Sweden diagnosed with new-onset pharmacologically treated type 2 diabetes between 2006 and 2012 were identified through the Swedish Prescribed Drug Register. They were followed until 31 December 2016 for ACM and until 31 December 2012 for CSM. Analyses were adjusted for age at diagnosis, sex, socioeconomic status, education, treatment and region. Associations were assessed using Cox regression analysis. RESULTS: In total, 138,085 individuals were diagnosed with type 2 diabetes between 2006 and 2012 and fulfilled inclusion criteria. Of these, 102,163 (74.0%) were native Swedes, 28,819 (20.9%) were first-generation immigrants and 7103 (5.1%) were second-generation immigrants with either one or both parents born outside Sweden. First-generation immigrants had lower ACM rate (HR 0.80 [95% CI 0.76, 0.84]) compared with native Swedes. The mortality rates were particularly low in people born in non-Western regions (0.46 [0.42, 0.50]; the Middle East, 0.41 [0.36, 0.47]; Asia, 0.53 [0.43, 0.66]; Africa, 0.47 [0.38, 0.59]; and Latin America, 0.53 [0.42, 0.68]). ACM rates decreased with older age at migration and shorter stay in Sweden. Compared with native Swedes, first-generation immigrants with ≤ 24 years in Sweden (0.55 [0.51, 0.60]) displayed lower ACM rates than those spending >24 years in Sweden (0.92 [0.87, 0.97]). Second-generation immigrants did not have better survival rates than native Swedes but rather displayed higher ACM rates for people with both parents born abroad (1.28 [1.05, 1.56]). CONCLUSIONS/INTERPRETATION: In people with type 2 diabetes, the lower mortality rate in first-generation non-Western immigrants compared with native Swedes was reduced over time and was equalised in second-generation immigrants. These findings suggest that acculturation to Western culture may impact ACM and CSM in immigrants with type 2 diabetes but further investigation is needed. Graphical abstract.

Beta-adrenergic receptor blockers and liver cancer mortality in a national cohort of hepatocellular carcinoma patients.

Background: ß-adrenergic signaling has been implicated in the pathology of hepatocellular carcinoma (HCC), but the evidence from clinical studies is limited. In this national population-based cohort study, we investigated the possible association of ß-adrenergic receptor blockers and cancer-specific mortality among patients with primary HCC diagnosed in Sweden between 2006 and 2014.Methods: Patients were identified from the Swedish Cancer Register (n = 2104) and followed until 31 December 2015. We used Cox regression to evaluate the association of ß-blockers dispensed within 90 days prior to cancer diagnosis, ascertained from the national Prescribed Drug Register, with liver cancer mortality identified from the Cause of Death Register, while controlling for socio-demographic factors, tumor characteristics, comorbidity, other medications and treatment procedures.Results: Over a median follow-up of 9.9 months, 1601 patients died (of whom 1309 from liver cancer). Compared with non-use, ß-blocker use at cancer diagnosis [n = 714 (predominantly prevalent use, 93%)] was associated with lower liver cancer mortality [0.82 (0.72-0.94); p = .005]. Statistically significant associations were observed for non-selective [0.71 (0.55-0.91); p = .006], ß1-receptor selective [0.86 [0.75-1.00); p = .049] and lipophilic [0.78 (0.67-0.90); p = .001] ß-blockers. No association was observed for hydrophilic ß-blockers [1.01 (0.80-1.28); p = .906] or other antihypertensive medications. Further analysis suggested that the observed lower liver cancer mortality rate was limited to patients with localized disease at diagnosis [0.82 (0.67-1.01); p = .062].Conclusion: ß-blocker use was associated with lower liver cancer mortality rate in this national cohort of patients with HCC. A higher-magnitude inverse association was observed in relation to non-selective ß-blocker use.

Beta-Blocker Use and Lung Cancer Mortality in a Nationwide Cohort Study of Patients with Primary Non-Small Cell Lung Cancer.

BACKGROUND: ß-Adrenergic receptor blockers have been associated with improved survival among patients with different types of malignancies, but available data for patients with non-small cell lung cancer (NSCLC) are contradictory and limited to small hospital-based studies. We therefore aimed to investigate whether ß-blocker use at the time of cancer diagnosis is associated with lung cancer mortality in the largest general population-based cohort of patients with NSCLC to date. METHODS: For this retrospectively defined nationwide cohort study, we used prospectively collected data from Swedish population and health registers. Through the Swedish Cancer Register, we identified 18,429 patients diagnosed with a primary NSCLC between 2006 and 2014 with follow-up to 2015. Cox regression was used to estimate the association between ß-blocker use at time of cancer diagnosis ascertained from the Prescribed Drug Register and cancer-specific mortality identified from the Cause of Death Register. RESULTS: Over a median follow-up of 10.2 months, 14,994 patients died (including 13,398 from lung cancer). Compared with nonuse, ß-blocker use (predominantly prevalent use, 93%) was not associated with lung cancer mortality [HR (95% confidence interval): 1.01 (0.97-1.06)]. However, the possibility that diverging associations for specific ß-blockers and some histopathologic subtypes exist cannot be excluded. CONCLUSIONS: In this nationwide cohort of patients with NSCLC, ß-blocker use was not associated with lung cancer mortality when assessed in aggregate in the total cohort, but evidence for some ß-blockers is less conclusive. IMPACT: Our results do not indicate that ß-blocker use at lung cancer diagnosis reduces the cancer-specific mortality rate in patients with NSCLC.

International validation of Enhanced Recovery After Surgery Society guidelines on enhanced recovery for gynecologic surgery.

BACKGROUND: Enhanced Recovery After Surgery Society publishes guidelines on perioperative care, but these guidelines should be validated prospectively. OBJECTIVE: To evaluate the association between compliance with Enhanced Recovery After Surgery Gynecologic/Oncology guideline elements and postoperative outcomes in an international cohort. STUDY DESIGN: The study comprised 2101 patients undergoing elective gynecologic/oncology surgery between January 2011 and November 2017 in 10 hospitals across Canada, the United States, and Europe. Patient demographics, surgical/anesthesia details, and Enhanced Recovery After Surgery protocol compliance elements (pre-, intra-, and postoperative phases) were entered into the Enhanced Recovery After Surgery Interactive Audit System. Surgical complexity was stratified according to the Aletti scoring system (low vs medium/high). The following covariates were accounted for in the analysis: age, body mass index, smoking status, presence of diabetes, American Society of Anesthesiologists class, International Federation of Gynecology and Obstetrics stage, preoperative chemotherapy, radiotherapy, operating time, surgical approach (open vs minimally invasive), intraoperative blood loss, hospital, and Enhanced Recovery After Surgery implementation status. The primary end points were primary hospital length of stay and complications. Negative binomial regression was used to model length of stay, and logistic regression to model complications, as a function of compliance score and covariates. RESULTS: Patient demographics included a median age 56 years, 35.5% obese, 15% smokers, and 26.7% American Society of Anesthesiologists Class III-IV. Final diagnosis was malignant in 49% of patients. Laparotomy was used in 75.9% of cases, and the remainder minimally invasive surgery. The majority of cases (86%) were of low complexity (Aletti score ≤3). In patients with ovarian cancer, 69.5% had a medium/high complexity surgery (Aletti score 4-11). Median length of stay was 2 days in the low- and 5 days in the medium/high-complexity group. Every unit increase in Enhanced Recovery After Surgery guideline score was associated with 8% (IRR, 0.92; 95% confidence interval, 0.90-0.95; P<.001) decrease in days in hospital among low-complexity, and 12% (IRR, 0.88; 95% confidence interval, 0.82-0.93; P<.001) decrease among patients with medium/high-complexity scores. For every unit increase in Enhanced Recovery After Surgery guideline score, the odds of total complications were estimated to be 12% lower (P<.05) among low-complexity patients. CONCLUSION: Audit of surgical practices demonstrates that improved compliance with Enhanced Recovery After Surgery Gynecologic/Oncology guidelines is associated with an improvement in clinical outcomes, including length of stay, highlighting the importance of Enhanced Recovery After Surgery implementation.

Stress Resilience in Late Adolescence and Survival among Cancer Patients: A Swedish Register-Based Cohort Study.

BACKGROUND: Chronic stress has been suggested to play a role in cancer progression, but few studies have so far examined the potential influence of stress susceptibility. This national register-based cohort study utilizes a unique data source to investigate whether a stress resilience measure is associated with survival in cancer patients. METHODS: The cohort includes 9,318 Swedish male cancer patients born during 1952 to 1956 who had their stress resilience evaluated at a semistructured interview with a psychologist during mandatory conscription examination in late adolescence. RESULTS: Over a median of 3 years of follow-up from cancer diagnosis, a total of 2,541 patients died (2,322 from cancer). Overall, low (23%) compared with high (25%) stress resilience was associated with increased mortality (adjusted hazard ratio estimated by Cox regression 1.45; 95% confidence interval 1.28-1.65), particularly among men with carcinomas of the oropharynx (2.62, 1.24-5.56), upper respiratory tract (4.64, 1.05-20.41), and prostate (2.20, 1.04-4.62), as well as with Hodgkin lymphoma (3.52, 1.40-8.86). An association was evident for both cancer types associated with smoking (1.35, 1.10-1.66) and malignancies without an established smoking etiology (1.32, 1.12-1.56). The association between low stress resilience and mortality could partly be explained by tumor stage, marital status, and psychiatric comorbidity at cancer diagnosis. CONCLUSIONS: We observed an association between low stress resilience and mortality among men diagnosed with cancer, particularly oropharyngeal cancer, upper respiratory tract cancers, prostate cancer, and Hodgkin lymphoma. IMPACT: These results suggest that individual variation in stress resilience may influence survival among men with some cancer types.

Effect of lycopene supplementation on cardiovascular parameters and markers of inflammation and oxidation in patients with coronary vascular disease.

Oxidative stress and antioxidant deficiency play a pivotal role in initiation, development, and outcomes of cardiovascular disease. Pharmacokinetic parameters as well as the impact of highly bioavailable lycopene on cardiovascular variables, markers of inflammation and oxidation were investigated during a 30-day clinical trial in patients with coronary vascular disease. The patients were randomized into two major groups and were supplemented with a single 7 mg daily dose of lycopene ingested either in the form of lactolycopene (68 patients) or in the form of lycosome-formulated GA lycopene (74 patients). The endpoints included cardiovascular function parameters, serum lipids, and four markers of oxidative stress and inflammation. Ingestion of lycosome-formulated lycopene increased serum lycopene levels by 2.9- and 4.3-fold, respectively, after 2 and 4 weeks of the trial, whereas supplementation with lactolycopene upregulated serum lycopene by half-fold only after 4 weeks of ingestion. Lycosome formulation of lycopene resulted by the end of the trial in a threefold reduction in Chlamydia pneumoniae IgG and reduction to the same degree of the inflammatory oxidative damage marker. The decrease in oxidized LDL caused by lycosome-formulated lycopene was fivefold. Moreover, supplementation with lycosome-formulated lycopene was accompanied by a significant increase in tissue oxygenation and flow-mediated dilation by the end of the observational period. In contrast, lactolycopene did not cause any significant changes in the parameters studied. Therefore, enhanced bioavailability of lycopene promotes its antioxidant and anti-inflammatory functions and endorses a positive effect of lycopene on cardiovascular system.

Hospital admission with pneumonia and subsequent persistent risk of chronic kidney disease: national cohort study.

BACKGROUND: Although acute onset kidney complications associated with severe infections including pneumonia are well characterized, little is known about possible subsequent delayed risk of chronic kidney disease (CKD). PATIENTS AND METHODS: Associations between hospital admission with pneumonia in adulthood and raised risks of subsequent CKD were evaluated in a cohort of all male residents in Sweden born from 1952 to 1956 (n=284,198) who attended mandatory military conscription examinations in late adolescence (n=264,951) and were followed up through 2009. CKD and pneumonia were identified using Swedish national registers, and their associations were evaluated using Cox regression. Excluding the first year, the subsequent period was divided into ≤5, >5-≤15, and >15 years after hospital admission with pneumonia. Follow-up ended on the date of first incident diagnosis of kidney disease, death, emigration, or December 31,2009, whichever occurred first. RESULTS: During a median follow-up of 36.7 (interquartile range 35.3-37.9) years from late adolescence, 5,822 men had an inpatient pneumonia diagnosis without contemporaneous kidney disease. Among exposed men, 136 (2.3%) were later diagnosed with CKD compared with 2,749 (1.2%) of the unexposed. The adjusted hazard ratio for CKD in the first year after the first episode of pneumonia was 14.55 (95% confidence interval, 10.41-20.32), identifying early onset kidney complications and possibly pre-existing undiagnosed CKD. Starting follow-up 1 year after pneumonia to reduce the potential influence of surveillance bias and the risk of reverse causation, the adjusted hazard ratio for CKD in the first 5 years of follow-up was 5.20 (95% confidence interval, 3.91-6.93) and then attenuated with increasing time. CONCLUSION: Pneumonia among inpatients is associated with a persistently increased risk for subsequent CKD, with the highest risk during the years immediately after pneumonia. Health care professionals should be aware of this period of heightened risk to facilitate early diagnosis and secondary preventive interventions.

Appendicitis before Age 20 Years Is Associated with an Increased Risk of Later Prostate Cancer.

Background: Appendicitis before age 20 years has been observed to influence the risk of several inflammatory conditions, possibly through underlying immunological mechanisms. Inflammation has further been suggested to be involved in prostate cancer development. We therefore hypothesized that immunological characteristics signaled by appendicitis before late adolescence might influence the risk of later prostate cancer, and aimed to evaluate this association in a population-based study.Methods: We identified a large cohort of Swedish men who underwent assessment for military conscription around the age of 18 years (n = 242,573). Medical diagnoses at time of conscription were available through the Swedish Military Conscription Register. The Swedish Cancer Register was used to identify diagnoses of prostate cancer. Multivariable adjusted Cox regression analyses were used to estimate HR and 95% confidence intervals (95% CIs) for the association between appendicitis and prostate cancer.Results: During a median of 36.7 years of follow-up, 1,684 diagnoses of prostate cancer occurred. We found a statistically significant association between appendicitis and overall prostate cancer (adjusted HR 1.70; 95% CI, 1.08-2.67). The risk was notably increased for advanced (HR 4.42; 95% CI, 1.74-11.22) and lethal (HR 8.95; 95% CI, 2.98-26.91) prostate cancer.Conclusions: These results suggest that a diagnosis of appendicitis before adulthood potentially signals underlying immune characteristics and a pattern of inflammatory response relevant to prostate cancer risk.Impact: The study lends support to the proposed role of inflammation in prostate carcinogenesis, and adds another area of investigation potentially relevant to prostate cancer development. Cancer Epidemiol Biomarkers Prev; 27(6); 660-4. ©2018 AACR.

Acne in late adolescence and risk of prostate cancer.

Accumulating evidence suggest that Propionibacterium acnes may play a role in prostate carcinogenesis, but data are so far limited and inconclusive. The aim of this population-based cohort study was therefore to test whether presence of acne vulgaris during late adolescence is associated with an increased risk of prostate cancer later in life. We identified a large cohort of young men born in Sweden between 1952 and 1956, who underwent mandatory assessment for military conscription around the age of 18 (n = 243,187). Test information along with health data including medical diagnoses at time of conscription was available through the Swedish Military Conscription Register and the National Patient Register. The cohort was followed through linkages to the Swedish Cancer Register to identify the occurrence of prostate cancer until December 31, 2009. We used Cox regression to calculate adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) for the association between acne in adolescence and prostate cancer risk. A total of 1,633 men were diagnosed with prostate cancer during a median follow-up of 36.7 years. A diagnosis of acne was associated with a statistically significant increased risk for prostate cancer (adjusted HR: 1.43 95%; CI: 1.06-1.92), particularly for advanced stage disease (HR: 2.37 95%; CI 1.19-4.73). A diagnosis of acne classified as severe conferred a sixfold increased risk of prostate cancer (HR: 5.70 95% CI 1.42-22.85). Data from this large prospective population-based cohort add new evidence supporting a role of P. acnes infection in prostate cancer.