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Dental infections may be associated with subsequent atherosclerosis. In this regard we wanted to study if traces of Chlamydia pneumoniae can be found from deep periodontal pockets characterized with elevated collagenase-2 [matrix metalloproteinase (MMP)-8] levels in gingival crevicular fluid (GCF). Chlamydia pneumoniae has not previously been found to infect the oral cavity. Subgingival samples of dental plaque were collected from 31 teeth in 12 adult periodontitis patients by means of sterile curettes and examined for C. pneumoniae using a quantitative PCR technique. GCF samples were also collected and assayed by an immunofluorometric assay (IFMA) for MMP-8. Chlamydia pneumoniae RNA was demonstrated in a sample from one of the patients studied. Periodontal treatment eliminated the C. pneumoniae from the patient's subgingival dental plaque as well as reduced GCF MMP-8 level. Our findings suggest that C. pneumoniae, which is not normally thought to be involved in periodontitis, can be found in dental plaque. [ABSTRACT FROM AUTHOR]

Objective: The study objective was to investigate the association between female sex and 30-day mortality and postoperative complications in patients undergoing scheduled proximal thoracic aortic surgery in Sweden., Methods: In a nationwide population-based cohort study, all patients who underwent scheduled proximal thoracic aortic surgery in Sweden between 2016 and 2020 were included. The primary outcome measure was 30-day mortality. Secondary outcome measures included a combined end point including 30-day all-cause mortality, postoperative new-onset dialysis, perioperative stroke, or a prolonged need of postoperative ventilation (>48 hours). Logistic regression models and propensity score matching were used to estimate the association between female sex and primary and secondary outcomes adjusted for differences in baseline characteristics., Results: A total of 2000 patients (29% women) were analyzed. The crude 30-day all-cause mortality rate was higher in women compared with men (3.1% vs 1.4%, P < .001). Women were older at the time of surgery (65.6 vs 60.2 years, P < .001) and had more comorbidities and a larger maximum indexed aortic diameter (cm/m body height) at the time of surgery (3.4 ± 0.56 vs 3.0 ± 0.48, P < .001). The adjusted risk for 30-day mortality for women compared with men was not significant (odds ratio, 1.41; 95% CI, 0.70-2.83), and neither was the secondary composite end point (odds ratio, 0.89; 95% CI, 0.62-1.27). The propensity score-matched analysis showed similar results., Conclusions: Women who underwent proximal thoracic aortic surgery had a 2-fold higher unadjusted 30-day mortality risk, but the mortality risk was not significantly higher when age and comorbidities was taken into consideration., Competing Interests: Conflict of Interest Statement A.J. has received fees for consultancy or lectures from Werfen, Boehringer-Ingelheim, Portola, Baxter, and LFB, all unrelated to the present work. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Delirium is a common post-cardiac surgery complication that presents as acute changes in mental abilities with confused thinking and a lack of awareness of the surroundings. Delirium symptoms present in hyperactive- and hypoactive forms. Hypoactive delirium is often overlooked. Although nursing interventions are important in preventing and treating hypoactive delirium, studies focusing on nurses' experiences of hypoactive delirium are scarce. This study describes registered nurses' experiences of caring for patients with hypoactive delirium after cardiac surgery., Research Methodology/design: This was a qualitative descriptive study with an inductive approach. Data was collected through focus group interviews with 12 registered nurses with experience in caring for cardiac surgery patients with hypoactive delirium. The study complied with the Consolidated Criteria for Reporting Qualitative Research., Setting: A cardiac surgery department at a Swedish University Hospital., Findings: The analysis resulted in one main category; "Navigating the complexities of care when caring for patients with hypoactive delirium" and three sub-categories: "Challenges, "Nursing interventions" and "Promoting a team approach"., Conclusion: Delirium assessment and nursing interventions are perceived as essential yet demanding. when caring for patients with hypoactive delirium. Nursing interventions like maintaining the circadian rhythm and offering emotional support need to be prioritised by the nurses, in line with the autonomy of the registered nurse's profession. Moreover, the team around the patient is crucial for detecting and treating hypoactive delirium, and it is important to involve other professionals as well as the patient's relatives. Future research is needed to develop assessment instruments that more accurately capture hypoactive delirium in the postoperative setting., Implications for Clinical Practice: Despite the use of screening tools, nurses still experience challenges in detecting the symptoms of hypoactive delirium, indicating a need for more clinically effective screening tools for hypoactive delirium. Nursing interventions are emphasised in the care of patients with hypoactive delirium., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: Depression has been associated with increased cardiovascular morbidity and mortality. This study aimed to determine whether self-reported preoperative depressive symptoms were associated with worse long-term survival in patients undergoing cardiac surgery., Methods: This population-based, observational cohort study included patients who had undergone cardiac surgery at Karolinska University Hospital between 2013 and 2016. Self-reported data about depressive symptoms were collected using the Patient Health Questionnaire (PHQ-9) and other patient data were collected from the institutional surgical database and medical charts. Depression was defined as a PHQ-9 score ≥10. Weighted flexible parametric survival models were used to estimate the association between self-reported preoperative depressive symptoms and all-cause mortality and to quantify absolute survival differences., Results: Of the 1120 study patients, 162 (14.5%) had depressive symptoms before cardiac surgery. During a mean follow-up of 7.2 years (maximum, 9.2 years), there were 36 deaths in 1129 person-years (PYs) in the depressed group, compared to 160 deaths in 6889 PYs in the non-depressed group. In the adjusted analysis, self-reported depressive symptoms were associated with worse long-term survival (hazard ratio 1.66; 95% confidence interval 1.09-2.54) compared with no reported depressive symptoms. The absolute survival differences (% and 95% confidence interval) between the non-depressed and the depressed patients were -1.9 (-3.9 to 0.19), -5.7 (-11 to -0.01) and -9.7 (-19 to -0.4) after 1, 5 and 8 years, respectively., Conclusions: Self-reported preoperative depressive symptoms were associated with worse long-term survival following cardiac surgery and should be regarded as important as other classical risk factors., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: First-degree relatives of patients with abdominal aortic aneurysm (AAA) may have an increased risk of developing the disease. The primary aim was to report the prevalence of AAA in adult male and female offspring of patients with AAA. The secondary aim was to explore the efficiency of a registry-based detection route, and the third aim was to report contemporary prevalence in the population., Methods: Adult offspring of individuals with AAA and matched controls were identified through national registries. The examination included questionnaires and ultrasound examinations of the infrarenal aorta. Aortic pathology was defined as an aortic diameter ≥25 mm, AAA ≥30 mm., Results: The participation rate among male and female adult offspring was 64% (350/543) and 69% (402/583), respectively. A lower participation rate was found in male and female controls (51% and 52%). No difference in prevalence of AAA was observed between male adult offspring and controls (0.9%, c.i. 0.2 to 2.3%) or in the female population (prevalence of 0.2% in adult offspring and controls). Aortic pathology and previously diagnosed AAA were detected in 5.3% (c.i. 3.3 to 8.0%) of male adult offspring and 2.3% (c.i. 1.1 to 4.2%) in controls. Aortic pathology was more prevalent among adult offspring of females with AAA., Conclusion: The prevalence of AAA in the general population is low, but aortic pathology is notably higher among male first-degree relatives. Increased awareness should be directed towards individuals with a possible hereditary predisposition, particularly offspring of females with AAA and older smokers. Risk factor-based targeted screening of adult offspring of patients with AAA after registry-based detection should be further explored., Trial Registration: ClinicalTrials.gov identifier, NCT4623268., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd.)

Objectives: Postoperative delirium affects up to 50% of patients undergoing cardiac surgery. Delirium phenotypes are commonly divided into hyperactive and hypoactive, with hypoactive symptoms (reduced motor activity and withdrawal) often being overlooked due to their discreet character. Although the consequences of hypoactive delirium are severe, studies focusing on patients' experiences of hypoactive delirium are scarce. The aim of the study was to describe cardiac surgery patients' experiences of hypoactive delirium., Research Methodology/design: We used qualitative descriptive semi-structured interviews with an inductive, latent approach. Twelve patients with hypoactive symptoms of delirium after cardiac surgery were purposefully selected. Interview data were analysed by qualitative content analysis., Findings: Two themes based on eight sub-themes emerged. "Dream or reality in parallel worlds" included disturbing experiences of existing in parallel realities with cognitive effects, residual nightmares, and illusions that occasionally persisted after hospital discharge. "Managing the state of hypoactive delirium" included experiences of intellectually dealing with hypoactive delirium with assumptions of causes and cures, and through interactions like communicating with others., Conclusion: Participants experienced hypoactive delirium as extensive and long-lasting with perceptions of existing in parallel realities. The findings emphasize the need for healthcare professionals to have expertise in hypoactive delirium and its fluctuating course, as the delirium of many patients may be undetected and undiagnosed. Improving the use of screening tools for clinical practice is essential for the detection of hypoactive delirium, and a person-centred approach is needed to properly care for this group of patients., Implications for Clinical Practice: The challenges in the recognition of hypoactive delirium need to be emphasized because the syndrome is still overlooked. The use of screening tools in clinical practice is essential. A person-centred approach supports relationships between delirious patients and healthcare professionals., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: A lower elective repair rate among women with abdominal aortic aneurysms (AAAs) has been a consistent finding. Reasons behind this gender gap have not been thoroughly outlined., Methods: This was a retrospective multicenter cohort study (ClinicalTrials.gov: NCT05346289) at three European vascular centers in Sweden, Austria and Norway. Patients in surveillance with AAAs were consecutively identified starting from January 1, 2014, until reaching a total sample size of 200 women and 200 men. All individuals were followed for 7 years through medical records. Final treatment distributions and the proportion of "truly untreated" (surgically untreated despite reaching guideline-directed thresholds: 50 mm for women and 55 mm for men) were determined. In a complementary analysis, a universal 55-mm threshold was used. Gender-specific primary reasons behind untreated statuses were clarified. Eligibility for endovascular repair among the truly untreated was assessed in a structured computed tomography analysis., Results: Women and men had similar median diameters at inclusion (46 mm; P = .54) and at treatment decisions (55 mm; P = .36). After 7 years, the repair rate was lower among women (47% vs 57%). More women were truly untreated (26% vs 8%; P < .001) despite similar mean ages as for male counterparts (79.3 years; P = .16). With the 55-mm threshold, 16% women still classified as truly untreated. Similar reasons for nonintervention were captured for women and men (50% due to comorbidities alone, 36% morphology and comorbidity). The endovascular repair imaging analysis revealed no gender differences. Among truly untreated women, ruptures were common (18%), and mortality was high (86%)., Conclusions: Surgical AAA management differed between women and men. Women could be underserved in terms of elective repairs: one in every four women was untreated with over-the-threshold AAAs. The lack of obvious gender differences in eligibility analyses could imply unmeasured discrepancies (eg, in disease extent or patient frailty)., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Most methods to detect copy number variation (CNV) have high false positive rates, especially for small CNVs and in real-life samples from clinical studies. In this study, we explored a novel scatterplot-based method to detect CNVs in microarray samples. Methods: Illumina SNP microarray data from 13,254 individuals were analyzed with scatterplots and by PennCNV. The data were analyzed without the prior exclusion of low-quality samples. For CNV scatterplot visualization, the median signal intensity of all SNPs located within a CNV region was plotted against the median signal intensity of the flanking genomic region. Since CNV causes loss or gain of signal intensities, carriers of different CNV alleles pop up in clusters. Moreover, SNPs within a deletion are not heterozygous, whereas heterozygous SNPs within a duplication show typical 1:2 signal distribution between the alleles. Scatterplot-based CNV calls were compared with standard results of PennCNV analysis. All discordant calls as well as a random selection of 100 concordant calls were individually analyzed by visual inspection after noise-reduction. Results: An algorithm for the automated scatterplot visualization of CNVs was developed and used to analyze six known CNV regions. Use of scatterplots and PennCNV yielded 1019 concordant and 108 discordant CNV calls. All concordant calls were evaluated as true CNV-findings. Among the 108 discordant calls, 7 were false positive findings by the scatterplot method, 80 were PennCNV false positives, and 21 were true CNVs detected by the scatterplot method, but missed by PennCNV (i.e., false negative findings). Conclusion: CNV visualization by scatterplots allows for a reliable and rapid detection of CNVs in large studies. This novel method may thus be used both to confirm the results of genome-wide CNV detection software and to identify known CNVs in hitherto untyped samples., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Qiao, Levinson, Chen, Engelter, Erhart, Gaynor, McArdle, Schlicht, Krawczak, Stenman, Lindgren, Cole and Grond-Ginsbach.)

Objectives: Depression is common in patients with cardiac disease, and preoperative depression is associated with worse outcomes after cardiac surgery. Depression is also correlated with postoperative delirium (POD) after major surgery. However, the association between preoperative depression and POD after cardiac surgery is sparsely studied. The aim of this study was to investigate depression as a predictor for POD in cardiac surgery patients., Methods: This population-based cohort study included 1133 cardiac surgery patients in Stockholm 2013-2016. Depression was defined by the Patient Health Questionnaire-9, and POD was evaluated by assessing medical records for symptoms of POD according to Diagnostic and Statistical Manual of Mental Disorders criteria. The association between depression and POD was determined through multivariable logistic regression analysis., Results: A total of 162 (14%) individuals reported depressive symptoms preoperatively. The incidence of POD was 26% and highest among elderly patients. Among patients with depression, 34% developed POD. In the group of non-depressed patients, 24% developed POD. The overall adjusted odds of delirium were 2.19 times higher in individuals with depressive symptoms compared to controls (95% confidence interval 1.43-3.34). The onset of delirium was most common on Days 0-2 after surgery., Conclusions: This unique population-based study in patients undergoing cardiac surgery shows that preoperative depression is associated with POD in a large proportion of treated patients. The findings support the need for improved preoperative screening for depression, especially in younger patients, and enhanced clinical surveillance in the early postoperative period for all patients., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Aims: A diagnosis of depression in patients with coronary heart disease is associated with worse outcomes. This study examined the long-term risk for new onset of depression after coronary artery bypass grafting (CABG) compared to an age- and sex-matched control group from the general population., Methods and Results: In total, 125 418 primary isolated CABG patients and 495 371 matched controls were included from 1992 to 2017. The SWEDEHEART registry and three other national registers were used to acquire information about baseline characteristics and depression. The adjusted risk of depression was estimated by using Cox regression models adjusted for patient characteristics, and socioeconomic variables, described by hazard ratios (HR) and 95% confidence intervals (CI). In total, 6202 (4.9%) CABG patients and 17 854 (3.6%) controls developed depression. The cumulative incidence of depression was higher in CABG patients than in the control population [6.1%, 95% CI 6.0-6.3 vs. 4.7% (4.7-4.8), P < 0.0001]. Overall, the CABG group had a marginally increased adjusted risk of depression compared to controls [adjusted HR (aHR): 1.05 (1.01-1.09), P = 0.0091]. In age-specific analyses, the increased risk compared to controls was only present in patients <65 years [aHR: 1.19 (1.11-1.27), P <0.0001] and was only evident during the first 5 years after surgery., Conclusion: Patients who underwent CABG had a higher risk of new onset of depression compared to sex- and age-matched controls in the general population. The risk of depression was especially pronounced in younger patients during the first 5 years after surgery., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Abdominal aortic aneurysm (AAA) is a potentially life-threatening disease but the high mortality rate is linked to high age and comorbidity pattern. Depression is associated with increased mortality in the general population and individuals with cardiovascular diseases, but this is sparsely studied for AAA. The aim was to examine the prognostic impact of depressive symptoms on all-cause mortality in individuals with AAA and compare with findings in a general population of the same age and risk profile., Methods: Population-based prospective study including 36 616 participants (52.1% women) from the Trøndelag Health Study in Norway. A total of 9428 individuals died during a median follow-up of 10 years at ages 60-90 years. Depressive symptoms were defined by a Hospital Anxiety and Depression Scale-Depression score ≥8. Data on AAA diagnoses and death were obtained from medical records and national registers. HRs from Cox proportional hazard regression models are reported., Results: A total of 4832 (13.2%) individuals reported depressive symptoms, whereas 583 (1.6%) AAAs were identified. The adjusted hazard of death was 2.66 times higher in persons with AAA compared with the general population (95% CI 2.39 to 2.97). Overall, there was no significant adverse effect of depressive symptoms in individuals with AAA (HR 1.15;95% CI 0.88 to 1.51), whereas an increased risk was seen in the general population (HR 1.23;95% CI 1.17 to 1.30)., Conclusion: The overall risk of death was considerably higher in individuals with AAA compared with a general population of the same age and risk profile. Depressive symptoms did not significantly influence the risk of death in the AAA group., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: A decrease in ischemic stroke (IS) incidence has been observed in high income countries during the last decades. Whether this has influenced the occurrence of aphasia in IS is uncertain. We therefore examined the incidence rate and potentially related determinants of aphasia in IS., Methods: We prospectively examined consecutive patients admitted to hospital with first-ever acute IS between March 1, 2017, and February 28, 2018, as part of the Lund Stroke Register (LSR) Study, comprising patients from the uptake area of Skåne University Hospital, Lund, Sweden. Patients were assessed with National Institutes of Health Stroke Scale (NIHSS) at stroke onset. Presence of aphasia was evaluated with NIHSS item 9 (language). We registered IS subtypes and risk factors. To investigate possible temporal changes in aphasia incidence, we made comparisons with corresponding LSR data from 2005 to 2006. Incidence rates were calculated and adjusted to the European Standard Population (ESP) and to the Swedish population., Results: Among 308 included IS patients, 30% presented with aphasia (n = 91; 95% CI: 25-35), a proportion of aphasia in IS that was similar to 2005-2006. The incidence rate of aphasia was 31 per 100,000 person-years adjusted to the ESP (95% CI: 25-38 per 100,000 person-years) corresponding to a significant decrease of 30% between 2005-2006 and 2017-2018. The decrease was significantly more pronounced in men. The initial severity of aphasia remained unchanged, with the majority of patients having severe to global aphasia. No significant differences between vascular stroke risk factors were noted among stroke patients with or without aphasia., Conclusion: Even though the overall IS incidence rate has decreased during the first decades of the 21st century, the proportion of IS patients with aphasia at stroke onset remains stable at 30%. Aphasia continues to be an important symptom that needs to be considered in stroke care and rehabilitation., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Background and Purpose: The role of copy number variation (CNV) variation in stroke susceptibility and outcome has yet to be explored. The Copy Number Variation and Stroke (CaNVAS) Risk and Outcome study addresses this knowledge gap., Methods: Over 24,500 well-phenotyped IS cases, including IS subtypes, and over 43,500 controls have been identified, all with readily available genotyping on GWAS and exome arrays, with case measures of stroke outcome. To evaluate CNV-associated stroke risk and stroke outcome it is planned to: 1) perform Risk Discovery using several analytic approaches to identify CNVs that are associated with the risk of IS and its subtypes, across the age-, sex- and ethnicity-spectrums; 2) perform Risk Replication and Extension to determine whether the identified stroke-associated CNVs replicate in other ethnically diverse datasets and use biomarker data (e.g. methylation, proteomic, RNA, miRNA, etc.) to evaluate how the identified CNVs exert their effects on stroke risk, and lastly; 3) perform outcome-based Replication and Extension analyses of recent findings demonstrating an inverse relationship between CNV burden and stroke outcome at 3 months (mRS), and then determine the key CNV drivers responsible for these associations using existing biomarker data., Results: The results of an initial CNV evaluation of 50 samples from each participating dataset are presented demonstrating that the existing GWAS and exome chip data are excellent for the planned CNV analyses. Further, some samples will require additional considerations for analysis, however such samples can readily be identified, as demonstrated by a sample demonstrating clonal mosaicism., Conclusion: The CaNVAS study will cost-effectively leverage the numerous advantages of using existing case-control data sets, exploring the relationships between CNV and IS and its subtypes, and outcome at 3 months, in both men and women, in those of African and European-Caucasian descent, this, across the entire adult-age spectrum., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Depression is common in patients with cardiac disease. The importance of preoperative depression for development of postoperative delirium (POD) following cardiac surgery is not well known. The aim is to provide a summary estimate of depression as a predictor of POD following cardiac surgery., Methods: Systematic search of MEDLINE, EMBASE, Cochrane Library, Web of Science Core Collection and Psycinfo (Ovid) was performed from inception to October 2019, including cohort studies reporting odds ratios (ORs) and 95% confidence intervals (CIs) for POD following cardiac surgery in patients with preoperative depression compared to patients without depression. ORs and 95% CIs for POD were calculated using random-effects meta-analyses. Subgroup and sensitivity analyses were performed., Results: Seven studies were included with a combined study population of 2066 patients. The pooled prevalence of POD in the combined study population was 26% and preoperative depression was present in ∼9% of the total study population. All studies showed a positive association between preoperative depression and POD; and in 5 studies, the association was statistically significant. Patients with depression had a pooled OR of 2.31 (95% CI 1.37-3.90) for POD., Conclusions: This systematic review and meta-analysis confirm the findings that the previous association between preoperative depression and increased risk for developing POD reported for other patient groups is found also in cardiac surgery. Depression screening prior to cardiac surgery may be effective in identifying patients at higher risk for POD., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background Studies on intact abdominal aortic aneurysms mainly focus on treated patients, and data on untreated patients are sparse. The objective was to investigate sex differences among untreated patients regarding rupture and mortality rates and to determine predictors for these events. Sex-specific causes of death were evaluated. Methods and Results All patients ≥40 years diagnosed from 2001 to 2015 (n=32 393) with intact abdominal aortic aneurysms were identified in national registries; 60% (n=19 569) were untreated. Comorbid loads, crude rupture, and mortality rates were assessed. Predictors of 5-year rupture and mortality were analyzed in Cox models (sex, age, comorbidities, income, and marital status). The proportion of men and women with multiple comorbidities was similar. Within 5 years, 798 ruptures occurred (9.7% women versus 6.9% men, P <0.001). Ruptures were independently predicted by female sex (hazard ratio [HR], 1.23; 95% CI, 1.07-1.42; P =0.004), chronic obstructive pulmonary disease (HR, 1.36; 95% CI, 1.15-1.62; P <0.001), age (HR, 11.49; 95% CI, 5.68-23.25 for ≥80 years; P <0.001), and income (HR, 0.63; 95% CI, 0.53-0.75 for highest tertile; P <0.001). After 5 years, 56.5% women and 50.4% men were deceased. Mortality was not independently predicted by female sex. Rupture was the third most common cause of death (11.9% women versus 8.7% men; P <0.001). The median time-to-events was 2.8 years. Conclusions A considerable proportion of patients with intact abdominal aortic aneurysms in surveillance remain untreated. Despite surveillance algorithms, the healthcare system fails to prevent a high number of ruptures, especially among women. The time-to-event data highlight the urgency to develop more individualized surveillance.

Background: Depression is common in patients with cardiac disease. Depression is a risk factor for developing postoperative delirium, a common and serious complication to cardiac surgery., Objectives: The aim was to evaluate if screening tools for depression can be used to predict postoperative delirium after cardiac surgery., Methods: This was a prospective population-based pilot study including 26 patients between 23 and 80 years of age undergoing cardiac surgery in Sweden during 2018. The day before surgery the participants filled out the depression screening instruments Hospital Anxiety and Depression Scale and Patient Health Questionnaire. After discharge the patient charts were examined for documentation of symptoms of delirium., Results: Five (20%) patients screened positive regarding depression using the Hospital Anxiety and Depression Scale and 7 patients (27%) screened positive using The Patient Health Questionnaire. Four (22%) patients showed symptoms of postoperative delirium, none of them screened positive for depression prior to surgery., Conclusion: We found no difference between the questionnaires PHQ-9 and HADS regarding identifying depressive symptoms. Moreover, we found that post-operative delirium, to a certain extent, can be detected by reading the patient́s charts postoperatively. However, this pilot study showed that screening tools for delirium need to be better implemented., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background Depression is associated with cardiovascular diseases, but the evidence is scarce regarding depression and risk of abdominal aortic aneurysms (AAA). The aim was to determine whether individuals with depressive symptoms have increased risk of AAA. Methods and Results This population-based prospective study included 59 136 participants (52.4% women) aged 50 to 106 years from the HUNT (Norwegian Nord-Trøndelag Health Study). Symptoms of depression were assessed using the depression subscale of the Hospital Anxiety and Depression Scale (HADS). During a median follow-up of 13 years, there were 742 incident cases of AAA (201 women). A total of 6401 individuals (12.3%) reported depressive symptoms (defined as HADS depression scale [HADS-D]) ≥8) (52.5% women). The annual incidence rate of AAA was 1.0 per 1000 individuals. At all ages, the estimated proportion of individuals diagnosed with AAA was higher among those with depressive symptoms (log-rank test, P <0.001). People with HADS-D ≥8 were older than those with HADS-D<8 (median 57.8 versus 52.3 years, P <0.001) and a statistically significantly higher proportion of them ( P <0.001) were smokers, overweight or obese, and reported a history of coronary heart disease, diabetes mellitus, and hypertension. In a Cox proportional hazard regression model adjusted for these factors, individuals with depressive symptoms had a ≈30% higher risk of AAA than those without (hazard ratio, 1.32, 95% CI 1.08-1.61, P =0.007). Conclusions This study shows that individuals with depressive symptoms have significantly higher risk of incident AAA, after adjustments for established risk factors.

Background: Depression is common in patients with ischaemic heart disease and preoperative depression is a risk factor following coronary artery bypass grafting. The American Heart Association recommends depression screening in all patients with heart disease. Our aim was to assess the feasibility and results of a depression screening program in cardiac surgery patients., Methods: We introduced a depression screening project at the cardiac surgery department at Karolinska University Hospital and included patients between 2013 and 2016. Patients scheduled for elective surgery recieved the Patient Health Questionnaire (PHQ-9), a depression screening instrument, by mail approximately 2weeks before surgery. Urgent patients recieved the PHQ-9 on the ward. Baseline characteristics, medical history, and medications were collected from patient charts, and entered into a study database together with the results from the PHQ-9 questionaires., Results: During the study period, 2,512 patients underwent cardiac sugery; 1,133 (45%) completed PHQ-9. The response-rate in patients scheduled for elective surgery was 64%, and 15% in urgent patients. Fifteen per cent (15%) had a PHQ-9 score ≥10 suggestive of major depression. Reporting a PHQ-9 score ≥10 was twice as common in women as in men (23% vs 12%)., Conclusions: Systematic depression screening using PHQ-9 in cardiac surgery patients was feasible and not very resource-intensive. The project showed a satisfactory response-rate in elective patients, but adjustments to increase the response-rate in urgent patients are needed. Future studies should investigate if and how patients with symptoms of depression would benefit from depression management., (Copyright © 2018. Published by Elsevier B.V.)

Background: The aim was to investigate longitudinal changes in depression screening results by sex up to one year following cardiac surgery., Methods: We introduced a depression screening project using the Patient Health Questionnaire (PHQ-9) including patients between 2013-2016. Patients received the PHQ-9 prior to surgery, and at follow-up one year after surgery. We analyzed changes in PHQ-9 scores and screening status from baseline to 1-year follow-up., Results: Screening results were obtained in 1,133 patients prior to surgery, and after one year, 1,084 patients were alive and of those 897 (83%) patients completed the follow-up PHQ-9 questionnaire. A positive depression screen at baseline was twice as common in women compared to men. A total of 547 (92%) men and 173 (91%) women who were screening negative at baseline were still screening negative at 1-year follow-up. There was no difference between men and women. A lower proportion of men compared with women (44% vs. 61%) improved from screening positive at baseline to screening negative at 1-year follow-up (P=0.069). The total PHQ-9 score difference between baseline and one year had increased with 0.23 points among men and decreased with 0.68 points in women., Conclusions: We found that twice as many women as men had a positive depression screen at baseline, and that almost 10% of all who were screening negative at baseline, were screening positive after one year. An improvement in depressive symptoms (transition from a screening positive state to a negative screening state) was more common among women than men after one year of follow up., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: Metastatic papillary renal cell carcinoma (mPRCC) is understudied. The disease is often aggressive and specific treatment options are lacking., Patients and Methods: mPRCC patients (n = 86) referred to three academic centres in Sweden and Germany in the years 2005-2015 were retrospectively identified from medical records. Statistical analyses included Kaplan-Meier curves and calculation of Cox proportional hazards, generating hazard ratios with 95% confidence intervals. The aim of the study was to evaluate overall survival (OS) of mPRCC patients treated outside of clinical trials in the era of targeted agents (TA) and to identify clinically useful prognostic factors., Results: Median OS of all mPRCC patients was 11.2 months. TA were used in 77% of the patients and associated with younger age and better Eastern Cooperative Oncology Group performance status (PS). Brain metastases were common (28%). Patients with synchronous or metachronous metastases had similar OS. Variables independently associated with risk of death included age ≥60 years, worse PS and ≥3 metastatic sites. The MSKCC criteria did not provide additional prognostic information. A subgroup analysis of TA-treated patients revealed an association of lymph node metastasis with risk of death in addition to the other prognostic factors., Conclusion: OS in mPRCC remained short in the era of targeted agents. Age, PS, and number of metastatic sites provided independent prognostic information.

Background and Purpose- We sought to explore the effect of genetic imbalance on functional outcome after ischemic stroke (IS). Methods- Copy number variation was identified in high-density single-nucleotide polymorphism microarray data of IS patients from the CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) and SiGN (Stroke Genetics Network)/GISCOME (Genetics of Ischaemic Stroke Functional Outcome) networks. Genetic imbalance, defined as total number of protein-coding genes affected by copy number variations in an individual, was compared between patients with favorable (modified Rankin Scale score of 0-2) and unfavorable (modified Rankin Scale score of ≥3) outcome after 3 months. Subgroup analyses were confined to patients with imbalance affecting ohnologs-a class of dose-sensitive genes, or to those with imbalance not affecting ohnologs. The association of imbalance with outcome was analyzed by logistic regression analysis, adjusted for age, sex, stroke subtype, stroke severity, and ancestry. Results- The study sample comprised 816 CADISP patients (age 44.2±10.3 years) and 2498 SiGN/GISCOME patients (age 67.7±14.2 years). Outcome was unfavorable in 122 CADISP and 889 SiGN/GISCOME patients. Multivariate logistic regression analysis revealed that increased genetic imbalance was associated with less favorable outcome in both samples (CADISP: P=0.0007; odds ratio=0.89; 95% CI, 0.82-0.95 and SiGN/GISCOME: P=0.0036; odds ratio=0.94; 95% CI, 0.91-0.98). The association was independent of age, sex, stroke severity on admission, stroke subtype, and ancestry. On subgroup analysis, imbalance affecting ohnologs was associated with outcome (CADISP: odds ratio=0.88; 95% CI, 0.80-0.95 and SiGN/GISCOME: odds ratio=0.93; 95% CI, 0.89-0.98) whereas imbalance without ohnologs lacked such an association. Conclusions- Increased genetic imbalance was associated with poorer functional outcome after IS in both study populations. Subgroup analysis revealed that this association was driven by presence of ohnologs in the respective copy number variations, suggesting a causal role of the deleterious effects of genetic imbalance.

Background: Depression is common in patients with cardiovascular disease. The importance of preoperative depression for long-term survival following coronary artery bypass grafting (CABG) is not well known. The aim was to provide a summary estimate of the association between preoperative depression and long-term survival in adults who underwent CABG., Methods: We did a systematic search of MEDLINE, EMBASE, Cochrane Library, PsycINFO, Web of Science, and PubMed from inception to November, 2015, including cohort studies with at least one month of follow-up that reported hazard ratios (HR) and 95% confidence intervals (CI) for long-term all-cause mortality following CABG in patients with preoperative depression compared to non-depressed patients. Two reviewers independently extracted data on populations, exposure, outcome, risk of bias, and quality of evidence. We calculated HR and 95% CIs for all-cause mortality using random-effects meta-analyses and performed subgroup and sensitivity analyses., Results: Seven studies were included with a combined study population of 89,490 patients (4002 depressed/85,488 non-depressed). All studies observed a positive association between preoperative depression and all-cause mortality, and in 4 studies the association was statistically significant. Patients with depression had a pooled hazard ratio of 1.46 (95% CI: 1.23-1.73, p<0.0001) for all-cause mortality with moderate heterogeneity (I(2)=50.1%, p=0.061)., Conclusions: This systematic review and meta-analysis indicates that patients with preoperative depression are at increased risk for long-term, all-cause mortality following CABG compared with those without depression. Systematic screening for depression prior to cardiac surgery could identify those at higher risk., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: The impact of socioeconomic factors on mortality in patients with depression and cardiovascular disease is unknown. The aim was to study if socioeconomic factors modified the association between preoperative depression and survival following CABG., Methods: In a nationwide population-based cohort study, 22,930 patients who underwent CABG in Sweden between 2006 and 2013 were included from the SWEDEHEART register. The national Prescribed Drug Register was used to ascertain preoperative antidepressant use which was utilized as a proxy for depression. Educational level, income, and civil status were extracted from the Longitudinal integration database for health insurance and labor market studies. The primary outcome measure was all-cause mortality and was ascertained from the Cause of Death register. Cox regression and propensity score methods were used to estimate the risk for death while controlling for differences in baseline characteristics., Results: During a mean follow-up of 4.1 years, 340 (11%) patients died in the antidepressant group and 1923 (9.7%) patients died in the control group. The adjusted risk for death was higher in patients with preoperative antidepressant use (HR 1.27; 95% CI 1.13-1.43), and was practically unchanged after the addition of educational level, family disposable income, and civil status (HR 1.25; 95% CI 1.11-1.41). The results were confirmed in a propensity-score matched cohort, and in selected subgroup analyses., Conclusions: Among patients who underwent CABG in Sweden, preoperative antidepressant use was associated with worse survival even after controlling for socioeconomic factors. The clinical implication is that the impact of depression on mortality was not influenced by socioeconomic factors., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

The primary aim was to study the association between preoperative depression and long-term survival after coronary artery bypass grafting (CABG). Our secondary objective was to analyze the association between depression and cardiovascular events or all-cause mortality. In a nationwide, population-based, cohort study, all patients who underwent CABG in Sweden from 1997 to 2008 were included from the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies registry. Individual-level data were cross-linked from other national Swedish registers. Depression status and outcomes were obtained from the National Patient Register. The study population was 56,064 patients who underwent primary, isolated, nonemergent CABG. We identified 324 patients (0.6%) with depression before CABG. During a mean follow-up of 7.5 years, 114 patients (35%) with depression died, compared with 13,767 patients (25%) in the control group. Depression was significantly associated with increased mortality and the combined end point of death or rehospitalization for myocardial infarction, heart failure, or stroke (multivariate-adjusted hazard ratios [95% confidence intervals] 1.65 [1.37 to 1.99] and 1.61 [1.38 to 1.89], respectively). In conclusion, we found a strong and significant association between depression and long-term survival in patients with established ischemic heart disease who underwent CABG. Depression was also associated with an increased risk for a combination of death or rehospitalization for heart failure, myocardial infarction, or stroke., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: We hypothesized that depressed patients would have lower use of guideline-directed medical therapy for secondary prevention of cardiovascular events following coronary artery bypass grafting (CABG)., Methods: We included all patients who underwent primary isolated CABG in Sweden between 2006 and 2008. We cross-linked individual level data from national Swedish registers. Preoperative depression was defined as at least one antidepressant prescription dispensed before surgery. We defined medication use as at least two dispensed prescriptions in each medication class (antiplatelet agents, beta-blockers, angiotensin-converting enzyme inhibitors (ACEI)/angiotensin II receptor blocker (ARB), and statins) within a rolling 12 month period. We calculated adjusted risk ratios (RR) for the use of each medication class, and for all four classes, after one and four years, respectively., Results: During the first year after CABG, 93% of all patients (n = 10,586) had at least two dispensed prescriptions for an antiplatelet agent, 68% for an ACEI/ARB, 91% for a beta-blocker, and 92% for a statin. 57% had prescriptions for all four medication classes. After four years (n = 4034), 44% had filled prescriptions for all four medication classes. Preoperative depression was not significantly associated with a lower use of all four medication classes after one year (RR 0.98, 95% confidence interval (CI) 0.93-1.03) or after four years (RR 0.97, 95% CI 0.86-1.09)., Conclusions: Preoperative depression was not associated with lower use of guideline-directed medical therapy for secondary prevention after CABG. These findings suggest that the observed higher mortality following CABG among depressed patients is not explained by inadequate secondary prevention medication.

Systemic inflammation has been suggested to impact on the prognosis of metastatic renal cell carcinoma (mRCC). We undertook a retrospective analysis of patients with mRCC treated at Akademiska University Hospital in Sweden during the years 2005-2012 to assess the possible prognostic significance of inflammation-related factors including serum albumin, platelet count, weight loss and C-reactive protein (CRP). The Memorial Sloan-Kettering Cancer Center (MSKCC) criteria for prognosis of mRCC and ECOG performance status were assessed for all patients. Overall survival (OS) and progression-free survival (PFS) were calculated according to Kaplan-Meier, and Cox proportional hazards regression was used for uni- and multivariate analyses. The median OS of all patients (n=84) was 20 months. Univariate analysis identified low serum albumin (HR=4.17, p<0.001), elevated platelet count (HR=2.98, p<0.001) and patient-reported weight loss prior to diagnosis of mRCC (HR=2.73, p<0.001), in addition to MSKCC (HR=3.35, p=0.0088) to be associated with shorter OS. CRP did not significantly affect OS. Serum albumin retained prognostic significance for OS in multivariate analysis (HR=2.72, p=0.015). In patients treated with an angiogenesis-targeted agent (n=47), low serum albumin level (HR=4.63, p<0.001) and elevated platelet count (HR=2.11, p=0.022) were associated with shorter PFS. In contrast, CRP, weight loss and MSKCC risk group did not significantly affect PFS. In multivariate analysis serum albumin remained associated with PFS (HR=3.92, p=0.0035). Our findings identify serum albumin as an independent prognostic factor for patients with mRCC treated with angiogenesis-targeted therapy.

Background: Depression is common in patients with coronary artery disease and is associated with increased cardiovascular morbidity and mortality. Previous reports on the relationship between antidepressant use before coronary artery bypass grafting (CABG) and survival are conflicting. Our aim was to study the association between preoperative antidepressant use and survival following CABG., Methods: We identified all patients who underwent primary isolated non-emergent CABG in Sweden between 2006 and 2008. We used the SWEDEHEART registry and the Swedish National Patient Register to acquire information about baseline characteristics, and the national Prescribed Drug Register to obtain data regarding exposure, defined as at least one antidepressant prescription dispensed before surgery., Results: Of the 10,884 patients identified, 1171 (11%) were treated with antidepressants before surgery. Unadjusted 4-year survival was 89% in the antidepressant group compared with 92% in the group without antidepressant use (p=0.002). After multivariable adjustment, antidepressant use was associated with increased mortality (hazard ratio [HR] 1.45; 95% confidence interval [CI] 1.18-1.77), compared with non-use of antidepressants. Antidepressant use was also associated with an increased risk of rehospitalization (HR 1.40; 95% CI 1.19-1.65) and the composite endpoint rehospitalization or death (HR 1.44; 95% CI 1.26-1.65)., Conclusions: Among patients who underwent contemporary primary isolated CABG on a nonemergency basis in Sweden, there was a strong and statistically significant association between antidepressant use prior to surgery and long-term survival., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

This prospective study is the first one of its kind carried out in Finland, in which a simple technological platform was developed to merge traditional text messaging with an electronic patient information database. The technology has been tested for relaying two-way treatment messages in psychiatry provided by a central hospital offering secondary healthcare. Text messaging was found to be particularly well suited for young people who have to travel to the outpatient clinic over long distances or who face the risk of social exclusion. According to clinicians, the text message reminders sent between the visits, which take place every 1-2 months, can encourage the young people in question to stay in touch more frequently, which will help to improve their relationship with the hospital staff. The project is still in the pilot stage, and so far the most important results concern the development of the operating culture and, surprisingly enough, legal aspects. From the legal point of view, the hospital had to equate text messages with phone communications. For this reason, it was not possible to put the text messages into a separate register and they have not been archived either. The success or failure of the new innovative healthcare solution may, therefore, depend on both technological aspects and legal factors.

Matrix metalloproteinase-9 (MMP-9) has been shown to be involved in the development of diabetic nephropathy (DNP). We studied the levels, molecular forms, and degree of activation of urinary MMP-8, -9, -14, trypsin-1 and -2, as well as tumor-associated trypsin inhibitor (TATI) of DNP patients and healthy controls. Urinary samples were analyzed for MMPs by Western blotting and gelatin zymography and for trypsin-1, -2, and TATI by time-resolved immunofluorometric assays. Total MMP-8 immunoreactivity, the proportion of active MMP-9, and gelatinolytic activity in urine were significantly higher in DNP patients than in controls. In urine of DNP patients the proportion of active polymorphonuclear neutrophil (PMN)-type (but not fibroblast-type) MMP-8 was increased. MMP-8 and MMP-9 were found to form high molecular weight complexes in DNP urine. Total immunoreactivity of soluble urinary MMP-14 and the levels of trypsin (TRY)-1 and TRY-2, but not of TATI, were also significantly increased in DNP. Zymography, Western blotting, and immunofluorometric analysis of DNP urine showed a significant association especially between activation of MMP-9 as well as PMN-type MMP-8 and TRY-2. Our findings suggest that a trypsin-MMP cascade is involved in the pathogenesis of DNP, which may offer new possibilities for diagnosis and treatment of DNP with MMP inhibitors.

Purpose: To study the proteolytic phenomena contributing to the pathogenesis of keratoconus, corneal enzymes with potential to cleave fibrillar collagen were studied., Methods: Immunohistochemical labeling was undertaken of conventional and novel mammalian collagenases (MMP-1, -2, -8, -13, and -14) of the matrix metalloproteinase (MMP) family and other collagenolytic proteinases of the serine (human trypsin-2) and cysteine (cathepsin K) endoproteinase families. The results were analyzed using a semiquantitative scoring system., Results: Labeling of MMP-8 was moderate in healthy controls, but weak in keratoconus. Moderate MMP-2 and weak MMP-14 expressions were similar in controls and keratoconus. MMP-1 was slightly overexpressed in keratoconus. In contrast, MMP-13 was weak in controls compared to moderate in keratoconus and human trypsin-2 and cathepsin K were moderate in controls and strong in keratoconus., Conclusions: The collagenolytic milieu of human cornea is more complex than expected. Mesenchymal isoform of MMP-8 (ie, collagenase-2) participates in normal tissue remodeling, which may be impaired in keratoconus. MMP-2 (gelatinase A with interstitial collagenase activity) and MMP-14 (membrane-type MMP type I with collagenolytic potential) seem to be constitutively expressed and probably play a role in normal corneal remodeling. The most prominent changes in keratoconic cornea were observed in collagenase MMP-13 (ie, collagenase-3), and particularly, in cathepsin K and human trypsin-2, which were strongly expressed in keratoconus suggesting a role in intra- and extracellular pathological collagen destruction, respectively. This may contribute to stromal thinning characteristic for keratoconus.

It has traditionally been believed that only the human collagenases (matrix metalloproteinase-1, -8, and -13) are capable of initiating the degradation of collagens. Here, we show that human trypsin-2 is also capable of cleaving the triple helix of human cartilage collagen type II. We purified human trypsin-2 and tumor-associated trypsin inhibitor by affinity chromatography whereas collagen type II was purified from cartilage extracts using pepsin digestion and salt precipitation. Degradation of type II collagen and gelatin by trypsin-2 was demonstrated with sodium dodecyl sulfate-polyacrylamide gel electrophoresis, zymography, and mass spectrometry, and tumor-associated trypsin inhibitor specifically inhibited this degradation. Although human trypsin-2 efficiently digested type II collagen, bovine trypsin did not. Furthermore, immunohistochemical staining detected trypsin-2 in the fibroblast-like synovial lining and in stromal cells of human rheumatoid arthritis synovial membrane. These findings were confirmed by reverse transcriptase-polymerase chain reaction and nucleotide sequencing. Trypsin-2 alone and complexed with alpha(1)-proteinase inhibitor were also detected in the synovial fluid of affected joints by time-resolved immunofluorometric assay, suggesting that trypsin-2 is activated locally. These results are the first to assess the ability of human trypsin to cleave human type II collagen. Thus, trypsin-2 and its regulators should be further studied for use as markers of prognosis and disease activity in rheumatoid arthritis.

Background: A rapid chair-side test based on the immunological detection of elevated levels of collagenase-2 (matrix metalloproteinase-8, MMP-8) in gingival crevicular fluid (GCF) was developed to identify and monitor the course and treatment of adult periodontitis., Methods: MMP-8 was determined in GCF from periodontitis (11 patients, 90 sites), gingivitis (10 patients, 58 sites) and healthy control (8 patients, 59 sites) sites (i) by a test stick incorporating monoclonal antibodies to two epitopes on MMP-8 and (ii) by measuring MMP-8 concentration by a quantitative immunofluorometric assay. Patients with adult periodontitis were treated by scaling and root planing (SRP) and received oral hygiene instructions. GCF MMP-8 testing and clinical measurements were done before and after SRP., Results: MMP-8 GCF levels and chair-side test differentiated periodontitis from gingivitis and healthy control sites. MMP-8 GCF levels > 1 mg/l and positive chair-side test identified especially severe periodontitis sites. A positive and negative test stick result, the outcome of which was rapidly detectable in 5 mins, in GCF correlated well with MMP-8 immunofluorometric assay analysis from the collected GCF samples and the severity of periodontitis. Scaling and root planing reduced the MMP-8 levels in severe periodontitis sites with positive MMP-8 test and gingival probing pocket depth (PD) > 5 mm before treatment. The test stick result and the quantitative assay were discrepant in only 18 of the 207 sites tested, thus agreement was very good (kappa = 0.81). With a threshold of 1 mg/l MMP-8 activity the chair-side test provided a sensitivity of 0.83 and specificity of 0.96 (n = 207)., Conclusion: The MMP-8 test can be used to differentiate periodontitis from gingivitis and healthy sites as well as to monitor treatment of periodontitis. A reduction in GCF MMP-8 levels and a change in test stick result provide a means to optimize patient control during maintenance of periodontal treatment.

A critical step in cancer growth and metastasis is the dissolution of the extracellular matrix surrounding the malignant tumor, which leads to tumor cell invasion and dissemination. Type I collagen degradation involves the initial action of collagenolytic matrix metalloproteinases (MMP-1, -8, and -13) activated by MMP-3 (stromelysin-1). The role of interactive matrix serine proteinases (MSPs), including tumor-associated trypsinogens, has been unclear in collagenolysis. Now, we provide evidence that the major isoenzyme of human tumor-associated trypsinogens, trypsin-2, can directly activate three collagenolytic proMMPs as well as proMMP-3. These proMMP activations are inhibited by tumor-associated trypsin inhibitor (TATI). Furthermore, we demonstrate that trypsin-2 efficiently degrades native soluble type I collagen, which can be inhibited by TATI. However, cell culture studies showed that trypsin-2 transfection into the HSC-3 cell line did not result in MMP-1, -3, -8, and -13 activation but affected MMP-3 and -8 production at the protein level. These findings indicate that human trypsin-2 can be regarded as a potent tumor-associated matrix serine protease capable of being the initial activator of the collagenolytic MMP activation network as well as directly attacking type I collagen.