The prevalence of chronic limb-threatening ischaemia (CLTI) is increasing and available data often derive from cohorts with various selection criteria. In the present study, we included CLTI patients and studied sex-related differences in their risk profile, vascular procedures, and long-term outcome. We analysed 199 953 unselected patients of the largest public health insurance in Germany (AOK: Local healthcare funds), hospitalized between 2010 and 2017 for a main diagnosis of CLTI. A baseline period of 2 years before index hospitalization to assess comorbidities and previous procedures, and a follow-up period until 2018 were included. Female CLTI patients were older (median 81.4 vs. 73.8 years in males; P < 0.001) and more often diagnosed with hypertension, atrial fibrillation, chronic heart failure, and chronic kidney disease. Male patients suffered more frequently from diabetes mellitus, dyslipidaemia, smoking, cerebrovascular disease, and chronic coronary syndrome (all P < 0.001). Within hospitalized CLTI patients, females represent the minority (43% vs. 57%; P < 0.001) and during index hospitalization, women underwent less frequently diagnostic angiographies (67 vs. 70%) and revascularization procedures (61 vs. 65%; both P < 0.001). Moreover, women received less frequently guideline-recommended drugs like statins (35 vs. 43%) and antithrombotic therapy (48 vs. 53%; both P < 0.001) at baseline. Interestingly, after including age and comorbidities in a Cox regression analysis, female sex was associated with increased overall-survival (OS) [hazard ratio (HR) 0.95; 95% confidence interval (CI) 0.94–0.96] and amputation-free survival (AFS) (HR 0.84; 95% CI 0.83–0.85; both P < 0.001). Female patients with CLTI were older, underwent less often vascular procedures, and received less frequently guideline-recommended medication. Nevertheless, female sex was independently associated with better OS and AFS during follow-up. An analysis of 199 953 unselected CLTI patients of the largest public health insurance in Germany (AOK) showed that female CLTI patients were older and display the minority of the hospitalized CLTI patients. During index hospitalization and during follow-up period, women underwent less frequently any vascular procedure (diagnostic angiography or revascularization procedures) and, moreover, received less frequently guideline-recommended drugs like statins or antithrombotic therapy. Interestingly, after including age and comorbidities in a Cox regression analysis, female sex was associated with increased OS and AFS.

Immune responses in plants are triggered by molecular patterns or elicitors, recognized by plant pattern recognition receptors. Such molecular patterns are consequence of host-pathogen interactions and the response cascade activated after their perception is known as pattern-triggered immunity (PTI). Glucans have emerged as key players in PTI, but the ability of certain glucans to stimulate defensive responses in plants remains understudied. This work focused on identifying novel glucan oligosaccharides as molecular patterns. The ability of various microorganism-derived glucans to prompt PTI responses was tested, revealing that specific microbial-derived molecules, such as short linear β-1,2-glucans, trigger this response in plants by increasing the production of reactive oxygen species (ROS), MAP kinase phosphorylation, and differential expression of defence-related genes in Arabidopsis thaliana. Pretreatments with β-1,2-glucan trisaccharide (B2G3) improved Arabidopsis defence against bacterial and fungal infections in a hypersusceptible genotype. The knowledge generated was then transferred to the monocotyledonous model species maize and wheat, confirming that these plants also respond to β-1,2-glucans, with increased ROS production and improved protection against fungal infections following B2G3 pretreatments. In summary, as with other β-glucans, plants perceive β-1,2-glucans as warning signals and stimulate defence responses against phytopathogens.

Aims: To provide population-based data on the prevalence and clinical significance of immune deficiency syndromes (IDS) associated with congenital heart disease (CHD). Methods and results: Utilizing administrative German Health System data the prevalence of increased susceptibility to infection (ISI) or confirmed IDS was assessed in CHD patients and compared with an age-matched non-congenital control group. Furthermore, the prognostic significance of IDS was assessed using all-cause mortality and freedom from emergency hospital admission. A total of 54 449 CHD patients were included. Of these 14 998 (27.5%) had ISI and 3034 (5.6%) had a documented IDS (compared with 2.9% of the age-matched general population). During an observation period of 394 289 patient-years, 3824 CHD patients died, and 31 017 patients experienced a combined event of all-cause mortality or emergency admission. On multivariable Cox proportional-hazard analysis, the presence of ISI [hazard ratio (HR): 2.14, P < 0.001] or documented IDS (HR: 1.77, P = 0.035) emerged as independent predictors of all-cause mortality. In addition, ISI and confirmed IDS were associated with a significantly higher risk of emergency hospital admission (P = 0.01 for both on competing risk analysis) during follow-up. Conclusion: Limited immune competence is common in CHD patients and associated with an increased risk of morbidity and mortality. This highlights the need for structured IDS screening and collaboration with immunology specialists as immunodeficiency may be amenable to specific therapy. Furthermore, studies are required to assess whether IDS patients might benefit from intensified antibiotic shielding or tailored prophylaxis.

Background: Amiodarone has a profound adverse toxicity profile. Large population-based analyses quantifying the risk of thyroid dysfunction (TD) in adults with and without congenital heart disease (ACHD) are lacking. Methods: All adults registered with a major German health insurer (≈9.2 million members) with amiodarone prescriptions were analyzed. Occurrence of amiodarone-associated TD was assessed. Results: Overall, 48,891 non-ACHD (37% female; median 73 years) and 886 ACHD (34% female; median 66 years) received amiodarone. Over 184,787 patient-years, 10,875 cases of TD occurred. The 10-year risk for TD was 38% in non-ACHD (35% ACHD). Within ACHD, compared to amiodarone-naïve patients, the hazard ratio (HR) for TD was 3.9 at 4 years after any amiodarone exposure. TD was associated with female gender (HR 1.42, p < 0.001) and younger age (HR 0.97 per 10 years, p = 0.009). Patients with congenital heart disease were not at increased risk (HR 0.98, p = 0.80). Diagnosis of complex congenital heart disease, however, was a predictor for TD (HR 1.56, p = 0.02). Amiodarone was continued in 47% of non-ACHD (38% ACHD), and 2.3% of non-ACHD (3.5% ACHD) underwent thyroid surgery/radiotherapy. Conclusions: Amiodarone-associated TD is common and comparable in non-ACHD and ACHD. While female gender and younger age are predictors for TD, congenital heart disease is not necessarily associated with an elevated risk.