Maribavir for treatment of cytomegalovirus infection in a liver-transplanted patient.

Cytomegalovirus infection (CMV) can be fatal for organ transplant recipients as shown in this case report. Maribavir is a recently approved drug, which can be used for therapy-refractory CMV infection or when other treatment options cannot be used. The patient in this case report was a CMV-infected liver transplant recipient, who developed a severe erythema and high CMV DNA during valganciclovir therapy. Toxic epidermal necrolysis was suspected. The patient was treated with maribavir, and both CMV DNA and the skin normalised. This case illustrates that maribavir is a useful alternative to other antiviral drugs for CMV infection.

Symptoms at stroke onset as described by patients: a qualitative study.

BACKGROUND: Stroke is a common and severe disease that requires prompt care. Symptom expressions as one-sided weakness and speech difficulties are common and included in public stroke campaigns. For some patients stroke can present with subtle and less common symptoms, difficult to interpret. The symptom severity assessed by the National Institutes of Health Stroke Scale has decreased, and symptoms at onset may have changed. Therefore, we aimed to investigate how patients describe their symptoms at the onset of a first-time stroke. METHODS: The study used a qualitative descriptive design and conventional content analysis. Data were collected through recorded interviews with 27 patients aged 18 years and older hospitalised with a first-time stroke between October 2018 and April 2020. Data were analysed on a manifest level. RESULTS: Symptoms at stroke onset were presented in two themes: Altered Reality and Discomfort and Changed Body Functions and described in five categories. Various types of symptoms were found. All symptoms were perceived as sudden, persistent, and never experienced before and this appear as a "red thread" in the result. Regardless of symptom expressions, no specific symptom was described as more severe than another. CONCLUSIONS: Stroke symptoms were described with a variety of expressions. Many described complex symptoms not typical of stroke, which can make it difficult to recognise the symptoms as a stroke and delay medical care. Public stroke campaigns should emphasize the importance of seeking medical care at the slightest suspicion of stroke and could be designed to help achieve this.

Technique efficacy and complications after ablation as first surgical intervention for hepatocellular carcinoma: A nationwide database study.

INTRODUCTION: Despite limited evidence, technique efficacy and complications may be important short-term outcomes after ablation for hepatocellular carcinoma (HCC). We aimed to report these outcomes after ablation as the first surgical intervention for HCC. METHODS: This nationwide cohort study was based on data from the Danish Liver and Biliary Duct Cancer Database and medical records. Variables associated with outcomes were investigated using logistic regression. RESULTS: From 2013 to 2023, 433 patients were included of which 79% were male, 73% had one tumor, and 90% had cirrhosis. Complete ablation was achieved after percutaneous, laparoscopic, and open approach in 84%, 100%, and 96% of the procedures, respectively. Most patients did not experience complications (76%). Open ablation compared with percutaneous was associated with higher risk of complications in multivariable adjusted analysis (Clavien-Dindo grade 2-5 (odds ratio 5.34, 95% confidence interval [2.36; 12.08]) and 3B-5 (5.70, [2.03; 16.01]), and lower risk of incomplete ablation (0.19 [0.05; 0.65]). Number of tumors ≥3 was associated with a higher risk of incomplete ablation (3.88, [1.45; 10.41]). Tumor diameter ≥3 cm was associated with increased risk of complications grade 2-5 (2.84, [1.29; 6.26]) and 3B-5 (4.44, [1.62; 12.13]). Performance status ≥2 was associated with risk of complications grade 3B-5 (5.98, [1.58; 22.69]). Tumor diameter was not associated with technique efficacy. CONCLUSION: Open ablation had a higher rate of complete ablation compared with percutaneous but was associated with a higher risk of complications. Tumor diameter ≥3 cm and performance status ≥2 were associated with a higher risk of complications.

Prevalence of hyperthyroidism and hypothyroidism in liver transplant recipients and associated risk factors.

The prevalence of hyperthyroidism and hypothyroidism and associated risk factors are unknown in liver transplant recipients. We aimed to determine the prevalence of hyperthyroidism and hypothyroidism and associated risk factors in liver transplant recipients and to compare it with controls from the general population. As part of the Danish Comorbidity in Liver Transplant Recipients (DACOLT) Study, all Danish liver transplant recipients over the age of 20 were invited for measurements of concentrations of thyrotropin and thyroid hormones. The prevalence of hyperthyroidism and hypothyroidism was compared to age- and sex-matched controls from the Copenhagen General Population Study. Using logistic regression adjusted for age, sex, smoking, and body-mass index, we investigated potential risk factors. We recruited 489 liver transplant recipients and 1808 controls. Among liver transplant recipients, 14 (2.9%) had hyperthyroidism compared with 21 (1.2%) of controls (adjusted odds ratio [aOR] 2.24, 95% confidence interval [CI] 1.05-4.75, P = 0.04), while 42 (5.7%) had hypothyroidism compared with 139 (7.7%) of controls (aOR 0.68, 95% CI 0.43-1.08, P = 0.10). Female sex, and autoimmune hepatitis and primary sclerosing cholangitis as causes of transplantation were associated with hyperthyroidism after adjustments. Age, female sex, and autoimmune liver diseases as cause of transplantation were associated with hypothyroidism after adjustments. DACOLT is registered in ClinicalTrials.gov (NCT04777032).

Early Results of a Screening Program for Skin Cancer in Liver Transplant Recipients: A Cohort Study.

(1) Background: Skin cancer is the most common cancer in transplant recipients. Timely and regular screening may reduce advanced disease. The study aimed to determine referral rates to screening, the incidence, and risk factors of skin cancer in a Danish liver transplant recipient cohort. (2) Methods: All first-time liver transplant recipients, >18 years old, attending outpatient care between January 2018 and December 2021 were included. The referral rates and incidence of skin cancer/preneoplastic lesions were calculated. Risk factors were assessed using Cox regression analyses. (3) Results: Of the 246 included recipients, 219 (89.0%) were referred to screening, and 102 skin cancer/preneoplastic lesions were diagnosed in 32 (15.6%) recipients. The IR of any skin cancer/preneoplastic lesion was 103.2 per 1000 person-years. BCC was the most frequent skin cancer followed by SCC, IR: 51.3 vs. 27.1 per 1000 person-years, respectively. No cases of MM were observed. The IR of actinic keratosis and Bowen's Disease were 48.1 vs. 13.2 per 1000 person-years, respectively. Time since transplantation was independently associated with skin cancer/preneoplastic lesions, HR (95%CI) 2.81 (1.64-4.80). (4) Conclusions: The study determined the incidence and risk factors of skin cancer/preneoplastic lesions in liver transplant recipients enrolled in a screening program, while demonstrating a high screening referral rate.

Self-reported symptom occurrence and distress, and psychological well-being after liver transplantation - a descriptive cross-sectional study of Danish recipients.

Introduction: Symptom distress and impaired psychological well-being after liver transplantation may lead to limitations in everyday activities and lowered health-related quality of life. The aim of this nationwide, descriptive, and cross-sectional study was to explore self-reported symptom occurrence and distress, among Danish liver transplant recipients, and their association with self-reported psychological well-being as well as demographic, and clinical characteristics. Methods: Liver transplant recipients transplanted from 1990 to 2022 were included. All recipients were asked to complete the Organ Transplant Symptom and Wellbeing instruments consisting of two instruments measuring self-reported symptom occurrence and distress, respectively, as well as self-reported psychological well-being by the Psychological General well-being instrument. Results: Of 511 invited recipients 238 responded: 116 women and 122 men with a median post-transplant follow-up of 7.5 years (IQR 3.6-14.2 years). The most common single symptoms reported were decreased libido (18%), diarrhea (10%), and headache (8%). Sleep problems were the most common transplant-specific domain. 41% of the recipients reported poor psychological well-being, especially those who had undergone transplantation within the last 5 years, women, and younger recipients. Discussion: In the interest of equity, the fact that women reported a higher level of symptom distress than men requires attention. Research on symptom management support is warranted with interventions focusing on how to alleviate symptom distress, which might increase long-term survival, which has not improved in recent decades.

Recurrence of Atrial Fibrillation in Patients With New-Onset Postoperative Atrial Fibrillation After Coronary Artery Bypass Grafting.

Importance: New-onset postoperative atrial fibrillation (POAF) occurs in approximately 30% of patients undergoing coronary artery bypass grafting (CABG). It is unknown whether early recurrence is associated with worse outcomes. Objective: To test the hypothesis that early AF recurrence in patients with POAF after CABG is associated with worse outcomes. Design, Setting, and Participants: This Swedish nationwide cohort study used prospectively collected data from the SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) registry and 3 other mandatory national registries. The study included patients who underwent isolated first-time CABG between January 1, 2007, and December 31, 2020, and developed POAF. Data analysis was performed between March 6 and September 16, 2023. Exposure: Early AF recurrence defined as an episode of AF leading to hospital care within 3 months after discharge. Main Outcomes and Measures: The primary outcome was all-cause mortality. Secondary outcomes included ischemic stroke, any thromboembolism, heart failure hospitalization, and major bleeding within 2 years after discharge. The groups were compared with multivariable Cox regression models, with early AF recurrence as a time-dependent covariate. The hypothesis tested was formulated after data collection. Results: Of the 35 329 patients identified, 10 609 (30.0%) developed POAF after CABG and were included in this study. Their median age was 71 (IQR, 66-76) years. The median follow-up was 7.1 (IQR, 2.9-9.0) years, and most patients (81.6%) were men. Early AF recurrence occurred in 6.7% of patients. Event rates (95% CIs) per 100 patient-years with vs without early AF recurrence were 2.21 (1.49-3.24) vs 2.03 (1.83-2.25) for all-cause mortality, 3.94 (2.92-5.28) vs 2.79 (2.56-3.05) for heart failure hospitalization, and 3.97 (2.95-5.30) vs 2.74 (2.51-2.99) for major bleeding. No association between early AF recurrence and all-cause mortality was observed (adjusted hazard ratio [AHR], 1.17 [95% CI, 0.80-1.74]; P = .41). In exploratory analyses, there was an association with heart failure hospitalization (AHR, 1.80 [95% CI, 1.32-2.45]; P = .001) and major bleeding (AHR, 1.92 [1.42-2.61]; P < .001). Conclusions and Relevance: In this cohort study of early AF recurrence after POAF in patients who underwent CABG, no association was found between early AF recurrence and all-cause mortality. Exploratory analyses showed associations between AF recurrence and heart failure hospitalization, oral anticoagulation, and major bleeding.

Fraction of exhaled nitric oxide is higher in liver transplant recipients than in controls from the general population: a cohort study.

Background: Fraction of exhaled nitric oxide with an expiratory flow of 50 mL/s (FENO50) is a biomarker of eosinophilic airway inflammation. Liver transplant recipients have an increased risk of pulmonary infections, but little is known about the burden of chronic pulmonary diseases in this group. We aimed to assess the prevalence of elevated FENO50 in liver transplant recipients and compare it to controls from the general population. Methods: FENO50 was measured in 271 liver transplant recipients from The Danish Comorbidity in Liver Transplant Recipients (DACOLT) study and 1,018 age- and sex-matched controls from The Copenhagen General Population Study (CGPS). Elevated FENO50 was defined as ≥25 or ≥50 parts per billion (ppb). The analyses were adjusted for known and suspected confounders. Results: The median age of the liver transplant recipients was 55 years (interquartile range (IQR) 46-64), and 58% were men. The liver transplant recipients had a higher median FENO50 than the controls [16 ppb (IQR 10-26) vs. 13 ppb (IQR 8-18.), p < 0.001]. Furthermore, the liver transplant recipients had a higher prevalence of elevated FENO50 (for FENO50 ≥25 ppb 27% vs. 11%, p < 0.001 and ≥50 ppb 4% vs. 2%, p = 0.02). The results were similar after adjusting for age, sex, smoking status, use of airway medication, and blood eosinophil counts [the adjusted odds ratio (OR) for FENO50 ≥25 ppb was 3.58 (95% CI: 2.50-5.15, p < 0.0001) and the adjusted OR for FENO50 ≥50 ppb was 3.14 (95% CI: 1.37-7.20, p = 0.007)]. Conclusion: The liver transplant recipients had elevated FENO50, implying increased eosinophilic airway inflammation. The clinical impact of this finding needs further investigation.

Long-term follow-up on patient-reported outcomes after supervised exercise training in individuals at risk of complications to type 2 diabetes.

AIMS: We investigated long-term changes of patient-reported outcomes after a supervised exercise intervention in individuals with type 2 diabetes (T2D). METHODS: In an intervention study without a control group, follow-up assessments were performed 12 months after initiating 12 weeks of physical exercise in individuals with T2D at intermediate or high risk of complications. Primary outcomes were health-related quality of life assessed with EQ-5D-5L, empowerment with Diabetes Empowerment Scale-Short Form, and self-reported physical activity with the Physical Activity Scale. Secondary outcomes were physical function (30-s chair-stand test) and working capacity (Aastrand or Graded Cycling Test). RESULTS: 153 participants completed follow-up (35% women, age (mean ± SD) 67 ± 11 years, body mass index 33.1 ± 5.9 kg/m2, glycated haemoglobin A1c 7.8 ± 3.7%). No changes were reported in health-related quality of life (index score p = 0.444, visual analogue scale p = 0.270), empowerment (p = 0.232), and moderate intensity physical activity (p = 0.917). Vigorous intensity physical activity decreased (mean (95% CI) -25.5 (-37.14; -13.94) min/day, p < 0.001). Physical function increased (p < 0.001) and working capacity decreased (Aastrand p = 0.002, Graded Cycling Test p = 0.039). CONCLUSIONS: Health-related quality of life, empowerment, and self-reported moderate intensity physical activity time remained elevated at the long-term follow-up after a supervised exercise intervention.

Elevated plasma apolipoprotein E levels in people living with HIV: Associations with biomarkers and HIV-specific risk factors.

BACKGROUND AND AIMS: Apolipoprotein E (apoE) plays a crucial role in cholesterol metabolism, and high levels of apoE in plasma are associated with cardiovascular disease and all-cause mortality. We aimed to assess if HIV is independently associated with high plasma apoE and to determine HIV-related risk factors for high plasma apoE. METHODS: We included 661 people with HIV (PWH) from the Copenhagen Comorbidity in HIV (COCOMO) study with available measurement of plasma apoE. COCOMO participants were frequency matched 1:1 on age and sex with controls from the Copenhagen General Population Study. High plasma apoE was defined as levels above the 90th percentile (66.2 mg/L). The association between HIV and high plasma apoE was assessed using logistic regression models. Among PWH, both linear and logistic regression models were used to determine HIV-specific risk factors for high plasma apoE. RESULTS: Mean age was 52 years and 89 % were male. Median plasma apoE was 49.0 mg/L in PWH and 43.3 mg/L in controls, p < 0.001. HIV was associated with higher plasma apoE after adjusting for potential confounders, including triglycerides (odds ratio 2.14 [95 % CI: 1.39-3.29], p < 0.001). In PWH, higher plasma apoE was associated with a previous AIDS-defining condition in linear models before adjustment for triglycerides and integrase strand transfer inhibitor use in fully adjusted linear models. CONCLUSIONS: PWH had higher plasma apoE than controls even after adjusting for triglycerides. Further studies are needed to elucidate the clinical impact of high plasma apoE in PWH.

Differences in toll-like receptor ligand-induced cytokine concentrations before and after solid organ transplantation: A prospective, observational cohort study in a clinical setting.

Reliable methods to assess immune function after solid organ transplantation (SOT) are needed to guide dosing of immunosuppression. We hypothesized that toll-like receptor ligand-induced cytokine concentrations would decrease post-transplantation due to the use of immunosuppressive medication. Furthermore, we hypothesized that induced cytokine concentrations pre-transplantation would be higher in recipients with episodes of acute rejection post-transplantation due to underlying immunological dispositions. We aimed to investigate toll-like receptor ligand-induced cytokine concentrations by TruCulture©, a standardized immunoassay, in SOT recipients before and 3 months after SOT and explored associations with methylprednisolone-treated acute rejections. We conducted a prospective, observational cohort study including 123 participants (67 liver, 32 kidney and 24 lung transplant recipients). Whole blood was stimulated for 22 h with: (A) Lipopolysaccharide (LPS), (B) Resiquimod, (C) Polyinosinic:polycytidylic acid (Poly I:C) and (D) a blank control. Cytokine concentrations (TNF-α, IL-1ß, IL-6, IL-8, IL-10, IL-12p40, IL-17A, IFN-α and IFN-γ) were measured by Luminex. 30 participants developed methylprednisolone-treated acute rejection at a median of 9 days (IQR 5-17) post-SOT. We found that all induced cytokine concentrations decreased post-SOT except from LPS-induced and Poly I:C-induced IL-10. The induced cytokine concentration pre-transplantation did not differ in recipients with or without acute rejection. In conclusion, the induced cytokine concentrations decreased for all stimuli post-SOT, except the anti-inflammatory cytokine IL-10. Importantly, recipients developing early acute rejection did not differ in induced cytokine concentrations pre-SOT. Thus, the use of a standardized assay in SOT is feasible in a clinical setting and may provide important information on the immune function post-SOT.

Gut Microbiota Alterations and Circulating Imidazole Propionate Levels Are Associated With Obstructive Coronary Artery Disease in People With HIV.

BACKGROUND: The impact of gut microbiota and its metabolites on coronary artery disease (CAD) in people with human immunodeficiency virus (PWH) is unknown. Emerging evidence suggests that imidazole propionate (ImP), a microbial metabolite, is linked with cardiometabolic diseases. METHODS: Fecal samples from participants of the Copenhagen Comorbidity in HIV infection (COCOMO) study were processed for 16S rRNA sequencing and ImP measured with liquid chromatography-tandem mass spectrometry. CAD severity was investigated by coronary computed tomography-angiography, and participants grouped according to obstructive CAD (n = 60), nonobstructive CAD (n = 80), or no CAD (n = 114). RESULTS: Participants with obstructive CAD had a gut microbiota with lower diversity and distinct compositional shift, with increased abundance of Rumiococcus gnavus and Veillonella, known producers of ImP. ImP plasma levels were associated with this dysbiosis, and significantly elevated in participants with obstructive CAD. However, gut dysbiosis but not plasma ImP was independently associated with obstructive CAD after adjustment for traditional and HIV-related risk factors (adjusted odds ratio, 2.7; 95% confidence interval, 1.1-7.2; P = .048). CONCLUSIONS: PWH with obstructive CAD displays a distinct gut microbiota profile and increased circulating ImP plasma levels. Future studies should determine whether gut dysbiosis and related metabolites such as ImP are predictive of incident cardiovascular events.

Immune responses to mRNA-based vaccines given as a third COVID-19 vaccine dose in people living with HIV-a literature review.

People living with HIV (PLWH) were not included in the first efficacy studies of mRNA vaccines against SARS-CoV-2. In this literature review, we investigate evidence of humoral and cellular immunity after a third dose of an mRNA vaccine in PLWH. We performed a literature search in PubMed, Embase, Web of Science and SCOPUS published between 1 January 2020 and 31 December 2022. Selection criteria were studies on immunological responses in PLWH, who were given an mRNA-based vaccine as a third vaccine dose against SARS-CoV-2. Eight articles complied with our selection criteria. All studies found a strong humoral response after the third dose. Five studies investigated cellular immunity and found an increased cellular response after the third vaccine dose in PLWH. No difference in humoral response was observed between PLWH and controls after three doses. However, some of the studies suggested a weaker cellular response among PLWH than in controls, which was associated with lower nadir or current CD4+ T-cell counts. In conclusion, we found evidence of strong humoral immunity in PLWH after receiving an mRNA-based COVID-19 vaccine as a third dose, while the cellular immunity may be impaired compared to controls.

Statin treatment after surgical aortic valve replacement for aortic stenosis is associated with better long-term outcome.

OBJECTIVES: The aim of this study was to evaluate the association between statin use after surgical aortic valve replacement for aortic stenosis and long-term risk for major adverse cardiovascular events (MACEs) in a large population-based, nationwide cohort. METHODS: All patients who underwent isolated surgical aortic valve replacement due to aortic stenosis in Sweden 2006-2020 and survived 6 months after discharge were included. Individual patient data from 5 nationwide registries were merged. Primary outcome is MACE (defined as all-cause mortality, myocardial infarction or stroke). Multivariable Cox regression model adjusted for age, sex, comorbidities, valve type, operation year and secondary prevention medications is used to evaluate the association between time-updated dispense of statins and long-term outcome in the entire study population and in subgroups based on age, sex and comorbidities. RESULTS: A total of 11 894 patients were included. Statins were dispensed to 49.8% (5918/11894) of patients at baseline, and 51.0% (874/1713) after 10 years. At baseline, 3.6% of patients were dispensed low dose, 69.4% medium dose and 27.0% high-dose statins. After adjustments, ongoing statin treatment was associated with a reduced risk for MACE [adjusted hazard ratio 0.77 (95% confidence interval 0.71-0.83). P < 0.001], mainly driven by a reduction in all-cause mortality [adjusted hazard ratio, 0.70 (0.64-0.76)], P < 0.001. The results were consistent in all subgroups. CONCLUSIONS: The results suggest that statin therapy might be beneficial for patients undergoing surgical aortic valve replacement for aortic stenosis. Randomized controlled trials are warranted to establish causality between statin treatment and improved outcome.

Anemia in liver transplant recipients: prevalence, severity, risk factors, and survival.

Information about anemia in liver transplant (LTx) recipients is scarce. We investigated the prevalence and severity of anemia before and within the first-year post-LTx, risk factors for having anemia before LTx, and 1-year survival according to anemia status before LTx. This retrospective cohort study received data from The Knowledge Center for Transplantation database at Rigshospitalet, Copenhagen, Denmark. Uni- and multivariate logistic regression were used to investigate factors associated with anemia and a Kaplan-Meier plot to illustrate the probability of survival. We included 346 first-time adult LTx recipients. The median age was 50 years (IQR: 42-57), and 203 (59%) were male. The prevalence of anemia before and 1-year post-LTx were 69 and 45%, respectively. Male sex (aOR 4.0 [95% CI: 2.2-7.2]; p < 0.001) and each unit increase in MELD score (aOR 1.2 [95% CI: 1.1-1.2]; p < 0.001) were positively associated with anemia before LTx. Compared to autoimmune liver diseases, LTx recipients with fulminant hepatic failure (aOR 0.03 [0.00-0.17]; p = 0.001) had lower odds for anemia. The 1-year survival in LTx recipients who had and did not have anemia before transplantation were 93 and 91% (p = 0.47). Anemia was frequent among LTx recipients, and anemia before LTx did not affect 1-year survival.

Clonal hematopoiesis of indeterminate potential in persons with HIV.

BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP) has been associated with older age, inflammation and with risk of coronary artery disease (CAD). We aimed to characterize the burden of CHIP, and to explore the association between CHIP, inflammatory markers, and CAD in older persons with HIV (PWH). METHODS: From the Copenhagen Comorbidity in HIV Infection (COCOMO) study, we included 190 individuals older than 55 years of age. We defined CHIP as variant allele fraction at least 2%. CAD was categorized according to the most severe coronary artery lesion on coronary computed tomography (CT) angiography as no coronary atherosclerosis; any atherosclerosis defined as at least 1% stenosis and obstructive CAD defined as at least 50% stenosis. RESULTS: In the entire population (median age 66 years, 87% men), we identified a total of 62 mutations distributed among 49 (26%) participants. The three most mutated genes were DNMT3A , TET2 , and ASXL1 , accounting for 49, 25, and 16% of mutations, respectively. Age and sex were the only variables associated with CHIP. IL-1ß, IL-1Ra, IL-2, IL-6, IL-10, soluble CD14, soluble CD163 and TNF-α were not associated with CHIP, and CHIP was not associated with any atherosclerosis or with obstructive CAD in adjusted analyses. CONCLUSION: In older, well treated, Scandinavian PWH, more than one in four had at least one CHIP mutation. We did not find evidence of an association between CHIP and inflammatory markers or between CHIP and CAD. CHIP is an unlikely underlying mechanism to explain the association between inflammation and CAD in treated HIV disease.

Renin-angiotensin system inhibition after surgical aortic valve replacement for aortic stenosis.

OBJECTIVE: The optimal medical therapy after surgical aortic valve replacement (SAVR) for aortic stenosis remains unknown. Renin-angiotensin system (RAS) inhibitors could potentially improve cardiac remodelling and clinical outcomes after SAVR. METHODS: All patients undergoing SAVR due to aortic stenosis in Sweden 2006-2020 and surviving 6 months after surgery were included. The primary outcome was major adverse cardiovascular events (MACEs; all-cause mortality, stroke or myocardial infarction). Secondary endpoints included the individual components of MACE and cardiovascular mortality. Time-updated adjusted Cox regression models were used to compare patients with and without RAS inhibitors. Subgroup analyses were performed, as well as a comparison between angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs). RESULTS: A total of 11 894 patients (mean age, 69.5 years, 40.4% women) were included. Median follow-up time was 5.4 (2.7-8.5) years. At baseline, 53.6% of patients were dispensed RAS inhibitors, this proportion remained stable during follow-up. RAS inhibition was associated with a lower risk of MACE (adjusted hazard ratio (aHR) 0.87 (95% CI 0.81 to 0.93), p<0.001), mainly driven by a lower risk of all-cause death (aHR 0.79 (0.73 to 0.86), p<0.001). The lower MACE risk was consistent in all subgroups except for those with mechanical prostheses (aHR 1.07 (0.84 to 1.37), p for interaction=0.040). Both treatment with ACE inhibitors (aHR 0.89 (95% CI 0.82 to 0.97)) and ARBs (0.87 (0.81 to 0.93)) were associated with lower risk of MACE. CONCLUSION: The results of this study suggest that medical therapy with an RAS inhibitor after SAVR is associated with a 13% lower risk of MACE and a 21% lower risk of all-cause death.

Postdischarge major bleeding, myocardial infarction, and mortality risk after coronary artery bypass grafting.

OBJECTIVE: To investigate the incidence and mortality risk associated with postdischarge major bleeding after coronary artery bypass grafting (CABG), and relate this to the incidence of, and mortality risk from, postdischarge myocardial infarction. METHODS: All patients undergoing first-time isolated CABG in Sweden in 2006-2017 and surviving 14 days after hospital discharge were included in a cohort study. Individual patient data from the SWEDEHEART Registry and five other mandatory nationwide registries were merged. Piecewise Cox proportional hazards models were used to investigate associations between major bleeding, defined as hospitalisation for bleeding, with subsequent mortality risk. Similar Cox proportional hazards models were used to investigate the association between postdischarge myocardial infarction and mortality risk. RESULTS: Among 36 633 patients, 2429 (6.6%) had a major bleeding event and 2231 (6.1%) had a myocardial infarction. Median follow-up was 6.0 (range 0-11) years. Major bleeding was associated with higher mortality risk <30 days (adjusted HR (aHR)=20.2 (95% CI 17.3 to 23.5)), 30-365 days (aHR=3.8 (95% CI 3.4 to 4.3)) and >365 days (aHR=1.8 (95% CI 1.7 to 2.0)) after the event. Myocardial infarction was associated with higher mortality risk <30 days (aHR=20.0 (95% CI 16.7 to 23.8)), 30-365 days (aHR=4.1 (95% CI 3.6 to 4.8)) and >365 days (aHR=1.8 (95% CI 1.7 to 2.0)) after the event. CONCLUSIONS: The increase in mortality risk associated with a postdischarge major bleeding after CABG is substantial and is similar to the mortality risk associated with a postdischarge myocardial infarction.

Incidence of bacterial respiratory infection and pneumonia in people with HIV with and without airflow limitation.

OBJECTIVES: We aimed to determine the incidence rate, pathogen composition, and risk factors, particularly airflow limitation, associated with bacterial respiratory infection and pneumonia in a prospective cohort of well-treated people with HIV (PWH) between 2015-2021. METHODS: We included 1007 PWH from the Copenhagen Comorbidity in HIV infection (COCOMO) study. Spirometry was performed at inclusion. Microbiology samples were collected prospectively. Cumulative incidence was determined by the Aalen-Johansen estimator. Cox proportional hazard models were used to calculate risk factors, adjusted for traditional and HIV-specific variables. RESULTS: The incidence rates of first bacterial respiratory infection and pneumonia were 12.4 (95% CI 9.7-15.5) and 5.5 (95% CI: 3.8-7.7) per 1000 person-years, respectively. The cumulative incidence of pneumonia was four times higher in PWH with airflow limitation (11.8% vs 3.2%, P <0.001). Risk factors for bacterial respiratory infection were airflow limitation (hazard ratio [HR] 2.9, [95% CI: 1.7-5.1], P <0.001), smoking (HR 2.3, [95% CI: 1.4-3.8], P <0.001), and previous AIDS-defining event (HR 2.0, [95% CI: 1.2-3.3], P = 0.009). For pneumonia, airflow limitation (HR 2.7, [95% CI: 1.2-6.3], P = 0.016), smoking (HR 2.5, [95% CI: 1.2-5.4], P = 0.016), and older age (HR 1.5, [95% CI: 1.1-2.1], P = 0.015) were identified as risk factors. CONCLUSIONS: Increased emphasis on airflow limitation prevention, including smoking cessation, may reduce the burden of bacterial respiratory infection and pneumonia in PWH.