Consequences of Losing Incidental Pulmonary Nodules to Follow-Up: Unmonitored Nodules Progressing to Stage IV Lung Cancer.

INTRODUCTION: Lung cancer is the leading cause of cancer-related death globally. Incidental pulmonary nodules represent a golden opportunity for early diagnosis, which is critical for improving survival rates. This study explores the impact of missed pulmonary nodules on the progression of lung cancer. METHODS: A total of 4,066 stage IV lung cancer cases from 2019 to 2021 in Danish hospitals were investigated to determine whether a chest computed tomography (CT) had been performed within 2 years before diagnosis. CT reports and images were reviewed to identify nodules that had been missed by radiologists or were not appropriately monitored, despite being mentioned by the radiologist, and to assess whether these nodules had progressed to stage IV lung cancer. RESULTS: Among stage IV lung cancer patients, 13.6% had undergone a chest CT scan before their diagnosis; of these, 44.4% had nodules mentioned. Radiologists missed a nodule in 7.6% of cases. In total, 45.3% of nodules were not appropriately monitored. An estimated 2.5% of stage IV cases could have been detected earlier with proper surveillance. CONCLUSION: This study underlines the significance of monitoring pulmonary nodules and proposes strategies for enhancing detection and surveillance. These strategies include centralized monitoring and the implementation of automated registries to prevent gaps in follow-up.

A rare case of sarcoid myelitis complicating Löfgren's syndrome.

Neurosarcoidosis is a rare and serious condition. Rapid diagnosis and treatment are crucial to prevent morbidity and mortality. When neurological symptoms are not present at the time of diagnosis, CNS involvement can be undetected. We present a case of neurosarcoidosis complicating Löfgren's syndrome and discus the challenges in diagnostics and treatment, that can be encountered.

Outcome of Incidental Pulmonary Nodules in a Real-World Setting.

OBJECTIVES: Early diagnosis of lung cancer is imperative to improve survival. Incidental pulmonary nodules (IPN) may represent early stages of lung cancer and appropriate follow-up and management of these nodules is important, but also very resource demanding. We aim to describe the results of the CT-based follow-up on a cohort of patients with IPN in terms of detected malignancies, the proportion undergoing invasive procedures, and the subsequent outcome. MATERIALS AND METHODS: Retrospective cohort study of patients in a CT IPN follow-up program who underwent a needle biopsy of the lung from 2018 to 2021 at Aarhus University Hospital. RESULTS: A total of 4181 patients with IPN were followed with CT control scans. Out of these 249 (6%) were diagnosed with lung cancer of which 224 (90%) were diagnosed as a result of the IPN follow-up. Seventy-five percent of the patients were diagnosed in stages I to II and curable treatment was possible in 77.9% of the patients. In the CT IPN follow-up program 449 patients underwent a CT guided needle biopsy. Out of these 190 patients underwent biopsy without the detection of malignancy, corresponding to 4.5% of the entire IPN population. CONCLUSION: The cumulated incidence of lung cancer in our population in the IPN follow-up program was 6%. The probability of malignancy when undergoing an invasive procedure on an IPN was 55.7% of which lung cancer was vastly predominant. The majority of lung cancers were diagnosed in an early and potentially curable stage.

Vitamin K2 Dependent Matrix Gla Protein Relating to Abdominal Aortic Aneurysm and Overall Mortality: A Combined Case Control and Cohort Study.

OBJECTIVE: Inactivation of matrix Gla protein (MGP), using vitamin K antagonists or vitamin K deficiency results in increased vascular calcification, which has been associated with increased risk of symptomatic or ruptured abdominal aortic aneurysm (AAA). Insufficient activation of MGP leads to increased levels of undercarboxylated forms of MGP, measured as a dephosphorylated, undercarboxylated MGP (dp-ucMGP) in plasma. This study aimed to investigate whether the level of inactivated MGP influenced the risk of having an AAA, the risk of AAA progression, and overall mortality. METHODS: This combined case control and cohort study was based on data from the randomised, clinically controlled Viborg Vascular (VIVA) screening trial. Cases (n = 487) with an AAA and controls (n = 189) with neither peripheral artery disease nor AAA, had their plasma quantified for dp-ucMGP. Plasma levels were compared with the presence of an AAA, AAA growth rate, need for repair, and overall mortality. dp-ucMGP was divided into tertiles in regression analyses. RESULTS: The plasma levels of dp-ucMGP were higher for AAA cases compared with controls (median of 517 pmol/L vs. 495 pmol/L, p = .036). Adjusted analyses regarding dp-ucMGP being predictive of AAA, AAA growth rate, and need for repair all failed to show correlation. Overall mortality for AAA cases exhibited a significant association for the third tertile of dp-ucMGP with a hazard ratio of 2.55 (95% CI 1.29 - 5.05) compared with the first tertile. Overall mortality for controls was not correlated with dp-ucMGP plasma levels. CONCLUSION: dp-ucMGP did not correlate with the risk of having an AAA, AAA growth rate, or risk of surgery. For people with an AAA, dp-ucMGP was correlated with an increased mortality risk for the highest tertile of dp-ucMGP. This could suggest a role for prophylactic measures with vitamin K2 supplements to people at risk of AAA.

Fluoroquinolones as a trigger for rupture of abdominal aortic aneurysm: A case-crossover analysis.

Fluoroquinolones (FQ) are associated with an increased risk of tendinopathy, including rupture. Our study aimed to investigate whether FQ use triggered the rupture of aortic aneurysms using a self-controlled design. We hypothesised that the use of FQ was associated with aortic rupture shortly after redeemed FQ prescriptions. Using nationwide data sources, we performed a case-crossover study of cases with ruptured aortic aneurysms. From 1996 to 2016, 58 persons presented with rupture of an aortic aneurysm and a redeemed prescription for any FQ within 28 days. 67% were men, and the median age was 77 years. Some 82.9% presented with a ruptured abdominal aneurysm. In our conditional regression, the crude OR for having rupture with a recent FQ redemption was 1.36 (CI 1.00-1.86). After adjusting for potential confounders, the OR was 1.35 (CI 0.98-1.85). Changing the hazard period to FQ redemption within 60 and 90 days, the OR was 2.16 (CI 1.70-2.76) and 2.21 (CI 1.78-2.75), respectively. In conclusion, we demonstrated an association between FQ use within 60 and 90 days and a diagnosis of ruptured aortic aneurysm.

Illness Perception After Heart Valve Surgery: Differences Among Men and Women.

BACKGROUND: Illness perception is composed of thoughts, ideas, and beliefs about illness, and a negative illness perception is known to be associated with poor outcomes. Among men and women, clinical outcomes after heart valve surgery are known to differ, but knowledge about differences in illness perception is sparse. OBJECTIVES: The aim of this study is to describe the differences in illness perception among men and women after open heart valve surgery and to identify sociodemographic and clinical characteristics associated with worse illness perception in men and women. METHODS: In a national cross-sectional study combined with register-based clinical and sociodemographic information, data on illness perception were collected with the Brief Illness Perception Questionnaire.Worse illness perception was defined as the worst quartile of each item of the Brief Illness Perception Questionnaire. Multiple logistic regression analyses were conducted to explore characteristics associated with worse illness perception. RESULTS: Of 1084 eligible patients, 32% (n = 349) completed the questionnaire (67% men; mean age, 68 years). Compared with men, women reported significantly worse scores of illness perception in 6 of 8 items. Furthermore, being female, age, length of stay, and comorbidity were associated with worse illness perception (worse quartile of scores). Age, higher educational level, and comorbidity were found to be associated with worse illness perception for men and length of stay for women. CONCLUSION: After open heart valve surgery, illness perception differs among men and women, with women having worse illness perception. Among the total population, being female, age, a longer length of stay, and comorbidity were also associated with worse illness perception.

Diabetes Is Not Associated with the Risk of Rupture Among Patients with Abdominal Aortic Aneurysms - Results From a Large Danish Register Based Matched Case Control Study From 1996 to 2016.

OBJECTIVE: Numerous studies have shown a paradoxical protective effect of diabetes on the development and progression of abdominal aortic aneurysm (AAA). The aim of this study was to investigate whether the protective role of diabetes on AAA extends to rupture, given the presence of an AAA. METHODS: This was a register based case control study. Patients with ruptured AAA (RAAA) were matched 1:1 with patients undergoing elective surgery for AAA by sex, age, and year of diagnosis. Multiple conditional logistic regression was performed to estimate the odds ratio (OR) associating a diagnosis of diabetes with RAAA. No protocol was registered. RESULTS: From 1996 to 2016, there were 6293 potential people with RAAA. A total of 898 people with a RAAA were excluded since no matching controls existed. This left 5 395 cases in the study. The cases had a median age of 75, and 85.4% were men. Diabetes was defined by hospital diagnosis or the redemption of antidiabetic prescriptions within one year. Comparing cases with controls and the presence of diabetes, a significant crude OR of 0.82 (95% confidence interval [CI] 0.71-0.95) was found. When adjusting for confounders OR increased to 0.97 (CI 0.83-1.14). Stratifying by age and year of diagnosis did not change the results markedly. OR associating RAAA with diabetes was significantly elevated in women (adjusted OR 1.82 [CI 1.17-2.81]). Of the 5395 cases, the overall 30 days mortality was 58% (n = 3145). Using Cox regression, a crude hazard ratio (HR) of 1.06 (CI 0.93-1.22) was found for the 30 day mortality and having diabetes compared with not having diabetes. Adjusting for index year, male sex, and age had little effect on this estimate (HR 1.11 [CI 0.97-1.28]). CONCLUSION: Diabetes was not found to protect against RAAA, given the presence of an AAA. Furthermore, diabetes did not increase the risk of dying within 30 days of RAAA.

Survival, Prevalence, Progression and Repair of Abdominal Aortic Aneurysms: Results from Three Randomised Controlled Screening Trials Over Three Decades.

AIM: The prevalence and mortality of abdominal aortic aneurysms (AAA) has been reported to decline. The aim of this study is to compare survival, prevalence, and repair rate of AAA in Denmark in the 1990s, the 2000s and the 2010s - and to examine any change in factors known to influence the prevalence. METHODS: Baseline status and up to 5-year outcomes of 34,079 general population men aged 65-74 were obtained from three RCTs; the Viborg study (1994-1998, n=4,860), the Viborg Vascular (VIVA) trial (2008-2011, n=18,748), and the Danish Cardiovascular (DANCAVAS) trial (2015-2018, n=10,471). After the millennium (VIVA and DANCAVAS) men with AAA were further offered low dose aspirin and statins. Follow-up data were not available for the DANCAVAS trial yet. RESULTS: Across the three decades, the AAA prevalence was 3.8% (Reference), 3.3% (p<0.001) and 4.2% (p=0.882), the proportion of smokers were 62%, 42% and 34% (p<0.001) amongst men with AAA, but AAA risk associations with smoking increased during the decades suggesting increased tobacco consumption of smokers. In addition, the proportions of attenders with ischemic heart disease or stroke increased significantly. The aneurysmal progression rate in the 1990s was 2.90 vs 2.98 mm/year in the 2000s (p=0.91). The need for preventive AAA repair increased insignificantly in the 2000s (Age adj. HR= 1.29, 95% C.I.: 0.95; 1.71, p=0.10), and mortality of men with screen-detected AAA was lower in the 2000s compared to the 1990s (Age-adj. HR= 0.28, 95% C.I.: 0.22; 0.36, p<0.001). CONCLUSION: The Danish prevalence of AAA today compares to the nineties. Unchanged aneurysmal progression rates combined with improved survival of men at risk of AAA leave them in longer time to develop an AAA, be diagnosed and to need later aneurysmal repair or experience rupture. CLINICAL TRIAL REGISTRATIONS: Viborg study: No possibility of registration in the nineties. VIVA: NCT00662480, URL: https://clinicaltrials.gov/show/NCT00662480, DANCAVAS: ISRCTN12157806, URL: http://www.isrctn.com/ISRCTN12157806.

High plasma microfibrillar-associated protein 4 is associated with reduced surgical repair in abdominal aortic aneurysms.

OBJECTIVE: Identifying biomarkers for abdominal aortic aneurysms (AAA) could prove beneficial in prognosis of AAA and thus the selection for treatment. Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein that is highly expressed in aorta. MFAP4 is involved in several tissue remodeling-related diseases. We aimed to investigate the potential role of plasma MFAP4 (pMFAP4) as a biomarker of AAA. METHODS: Plasma samples and data were obtained for 504 male AAA patients and 188 controls in the Viborg Vascular (VIVA) screening trial. The pMFAP4 levels were measured by Alphalisa. The Mann-Whitney U test assessed differences in pMFAP4 levels between the presence and absence of different exposures of interest. The correlation between pMFAP4 and aorta growth rate were investigated through spearman's correlation analysis. Immunohistochemistry and multiple logistic regression adjusted for potential confounders assessed the association between pMFAP4 and AAA. Multiple linear regression assessed the correlation between pMFAP4 and aorta growth rate. Cox regression and competing risk regression were used to investigate the correlation between AAA patients with upper tertile pMFAP4 and the risk of undergoing later surgical repair. RESULTS: A significant negative correlation between pMFAP4 and aorta growth rate was observed using spearman's correlation analysis (ρ = -0.14; P = .0074). However, this finding did not reach significance when applying multiple linear regression. A tendency of decreased pMFAP4 was observed in AAA using immunohistochemistry. Competing risk regression adjusted for potential confounders indicated that patients with upper tertile pMFAP4 had a hazard ratio of 0.51 (P = .001) for risk of undergoing later surgical repair. CONCLUSIONS: High levels of pMFAP4 are associated with a decreased likelihood of receiving surgical repair in AAA. This observation warrants confirmation in an independent cohort.

Arachidonic Acid, but Not Omega-3 Index, Relates to the Prevalence and Progression of Abdominal Aortic Aneurysm in a Population-Based Study of Danish Men.

BACKGROUND: Animal models support dietary omega-3 fatty acids protection against abdominal aortic aneurysm (AAA), but clinical data are scarce. The sum of red blood cell proportions of the omega-3 eicosapentaenoic and docosahexaenoic acids, known as omega-3 index, is a valid surrogate for long-term omega-3 intake. We investigated the association between the omega-3 index and the prevalence and progression of AAA. We also investigated associations between AAA and arachidonic acid, an omega-6 fatty acid that is a substrate for proinflammatory lipid mediators. METHODS AND RESULTS: We obtained blood samples from 498 AAA patients (maximal aortic diameter ≥30 mm) within a population-based ultrasound-screening trial in men and from 199 age-matched controls who screened negative. We determined the fatty acids of red blood cells by gas chromatography. During a median follow-up of 4.85 years, 141 AAA patients reached criteria for vascular surgical repair. Participants were high consumers of omega-3 (average omega-3 index: 7.6%). No significant associations were found for omega-3 index. In contrast, arachidonic acid in AAA patients was higher than in controls (P<0.001), and individuals in the upper tertile of arachidonic acid at baseline had higher probability of having AAA (odds ratio: 1.309; 95% confidence interval, 1.021-1.678; P=0.033). AAA patients at the upper tertile of arachidonic acid at baseline had a 54% higher risk of needing surgical repair during follow-up (hazard ratio: 1.544; 95% confidence interval, 1.127-2.114; P=0.007). CONCLUSIONS: Omega-3 index is unrelated to men with AAA from a country in which fish consumption is customarily high. Arachidonic acid is associated with AAA presence and progression. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00662480.

The Acute Effect of Loperamide on Ileostomy Output: A Randomized, Double-Blinded, Placebo-Controlled, Crossover Study.

High stoma output is a common problem in patients with ileostomy and can lead to dehydration and electrolyte disturbances. The first drug of choice to reduce stoma output is often loperamide. The aim was to assess the acute effect of loperamide on (a) ileostomy output in g/day, (b) gastrointestinal transit time and (c) patient-reported effects. A total of 12 patients completed this double-blinded, randomized, placebo-controlled, crossover study, consisting of a 3-day treatment period with loperamide 12 mg/day or placebo followed by the reverse after a washout period of 5-7 days. Patients collected stoma output and noted food and fluid intake over 48 hr and swallowed a capsule with radiopaque markers for the determination of gastrointestinal transit time over 24 hr. At the end of the study, patients were asked to report their treatment sequence. Ileostomy output was significantly reduced during loperamide treatment (p < 0.02) with a median of 16.5% (range -5% to 46%). Transit time was reduced significantly for the passage of 10% of the markers (p = 0.02), but not for 50% and 100% of the markers. Fifty-eight per cent (N = 7) of the patients reported the correct treatment sequence (p = 0.41). Loperamide 12 mg/day reduced ileostomy output statistically significantly, but with varying effects among patients and without reaching the clinical significance of 20% set-up by this study. Dose-response studies should be performed, and standard treatment doses of loperamide should be reassessed. The study was registered at ClinicalTrials.gov - NCT02266849.

Metformin treatment does not affect the risk of ruptured abdominal aortic aneurysms.

OBJECTIVE: Diabetes counteracts formation and rupture of abdominal aortic aneurysms, possibly through arterial matrix accumulation. Use of metformin, on the other hand, reduces arterial accumulation of matrix molecules. Consequently, we hypothesized that metformin treatment may reverse the protective role of diabetes on the development and course of aneurysms, that is, that metformin would be associated with aneurysm rupture among individuals with diabetes. METHODS: Using nationwide Danish registry data, we performed a nested case-control study on the association between long-term use of metformin and ruptured abdominal aortic aneurysm (RAAA). The source population was defined as all individuals in Denmark with diabetes. Cases were all individuals within the source population who were hospitalized with a primary diagnosis of RAAA. For each case, 10 controls matched by age and sex were randomly selected from the source population by risk set sampling. The main exposure measure was a cumulative dispensing of 1000 g of metformin between January 1995 and the index date. RESULTS: We identified 362 cases of RAAA during 1998 to 2013, of which 83.7% occurred in men with a median age of 74 years. In total, 22.4% of the case population were long-term metformin users compared with 28.8% of the controls. We found a statistically nonsignificant protective effect of long-term metformin use toward RAAA with crude odds ratio (OR) of 0.74 (confidence interval, 0.54-1.00). When adjusted for covariates, OR increased to 0.84 (confidence interval, 0.61-1.17). None of the subgroups had ORs deviating substantially from the main result. CONCLUSIONS: Metformin use does not increase the risk of RAAA among individuals with diabetes.

Glycated Hemoglobin Is Associated With the Growth Rate of Abdominal Aortic Aneurysms: A Substudy From the VIVA (Viborg Vascular) Randomized Screening Trial.

OBJECTIVE: An inverse association between abdominal aortic aneurysms (AAAs) and diabetes mellitus exists; however, the cause remains unknown. This study aimed to evaluate whether the degree of glycemia is associated with aneurysm growth. APPROACH AND RESULTS: The study was based on VIVA trial (Viborg Vascular), the randomized clinically controlled screening trial for abdominal aortic aneurysm in men aged 65 to 74 years in the Central Denmark Region. The screening included measurement of the abdominal aorta by ultrasound, analysis of glycated hemoglobin (HbA1c), and follow-up for ≤5 years for aneurysms <5 cm. Analyses were conducted using mixed-effect models. At baseline, VIVA screening identified 619 individuals (3.3%) with abdominal aortic aneurysms. A total of 103 individuals were referred for vascular evaluation, and after removal of additional individuals who were lost to follow-up or had missing blood samples, we were left with 319 individuals. Sixty-one individuals (19.1%) had diabetes mellitus. The median growth rate was 1.7 versus 2.7 mm/y in individuals with and without diabetes mellitus, respectively (P<0.001). We found a significant inverse association between aneurysmal growth rate and HbA1c in the total study population (P=0.002). Both crude and adjusted analyses identified slower growth for the group with the highest HbA1c tertile compared with the lowest HbA1c tertile. After 3 years, the mean difference was 1.8 mm (confidence interval, 0.98-2.64). Similar significant differences were observed in subgroup analysis of individuals without self-reported diabetes mellitus. CONCLUSIONS: We found an inverse association between the growth rate of abdominal aortic aneurysms and the level of HbA1c, indicating that long-lasting elevated blood sugar impairs aneurysmal progression in individuals with and without known diabetes mellitus.

Endovascular Treatment of an Aneurysmal Aberrant Systemic Artery Supplying a Pulmonary Sequestrum.

An aberrant systemic artery originating from the abdominal aorta supplying a pulmonary sequestration is a rare congenital malformation. This causes a left-to-left shunt. Symptoms include recurrent pneumonias, hemoptysis, and, in the long term, heart failure. Aneurysm of the aberrant vessel is rarely seen. Traditionally, treatment of pulmonary sequestrations includes ligation of the feeding vessel and lobectomy. A new promising treatment is an endovascular approach. Only a few cases describe endovascular treatment of pulmonary sequestration. This is the first published case of a giant aneurysmal branch from the abdominal aorta to the normal basal segments of the lung, successfully occluded with an Amplatzer Vascular Plug II (AVP II, St.Jude Medical, MN, USA) alone.

Antiplatelet therapy at the time of coronary artery bypass grafting: a multicentre cohort study.

OBJECTIVES: The purpose of this multicentre cohort study was to examine the relationship between antiplatelet therapy (APT) at the time of coronary artery bypass grafting (CABG) and postoperative bleeding complications, transfusion requirements and adverse cardiovascular events. METHODS: A matched-pair analysis was carried out on 6350 consecutive patients undergoing CABG at the three university hospitals in Western Denmark. Patients exposed to aspirin or clopidogrel within 5 days before surgery were compared with those not exposed to these drugs. The data used in the study were retrieved from the Western Denmark Heart Registry. RESULTS: Of the 6350 patients enrolled, 1846 (29%) had been exposed to aspirin or clopidogrel within 5 days prior to CABG (the APT group). Matching with the remaining 4504 (71%) patients of the control group resulted in 1132 pairs of patients. Patients in the APT group had greater mean chest tube drainage volumes (946 vs 775 ml; P < 0001) and greater transfusion requirements (ranging from 37.4-57.5 vs 29.8%; P < 0.0001) than control group patients. Preoperative aspirin therapy was not associated with greater reoperation rates (4.0 vs 3.9%; P = 0.005); nor was it an independent risk factor for severe postoperative bleeding >1000 ml (odds ratio [OR]: 1.07, 95% confidence interval [CI]: 0.55-1.34). Preoperative clopidogrel use, on the other hand, was associated with greater reoperation rates (10.2 vs 3.9% in the control group; P = 0.005) and was an independent predictor of severe postoperative bleeding (OR: 2.08, 95% CI: 1.55-2.80). Overall, preoperative APT had no significant effect on postoperative 30-day mortality, incidence of myocardial infarction, stroke or need for dialysis. CONCLUSIONS: Preoperative APT is associated with increased bleeding and greater transfusion requirements after CABG. Clopidogrel exposure is associated with greater reoperation rates and is an independent risk factor for severe postoperative bleeding.

Reoperation for bleeding in cardiac surgery.

At Odense University Hospital (OUH), 5-9% of all unselected cardiac surgical patients undergo reoperation due to excessive bleeding. The reoperated patients have an approximately three times greater mortality than non-reoperated. To reduce the rate of reoperations and mortality due to postoperative bleeding, we aim to identify risk factors that predict reoperation. A total of 1452 consecutive patients undergoing cardiac surgery using extracorporeal circulation (ECC) between November 2005 and December 2008 at OUH were analysed. Statistical tests were used to identify risk factors for reoperation. We performed a case-note review on propensity-matched patients to assess the outcome of reoperation for bleeding regarding morbidity and mortality. In total, 101 patients (7.0%) underwent surgical re-exploration due to excessive postoperative bleeding. Significant risk factors for reoperation for bleeding after cardiac surgery was low ejection fraction, high EuroSCORE, procedures other than isolated CABG, elongated time on ECC, low body mass index, diabetes mellitus and preoperatively elevated s-creatinine. Reoperated patients significantly had a greater increase in postoperative s-creatinine and higher mortality. Surviving reoperated patients significantly had a lower EuroSCORE and a shorter time on ECC compared with non-survivors. The average time to re-exploration was 155 min longer for non-survivors when compared with survivors.