"We've got to get out"-Strategies of human pathogenic fungi to escape from phagocytes.

Human fungal pathogens are a deadly and underappreciated risk to global health that most severely affect immunocompromised individuals. A virulence attribute shared by some of the most clinically relevant fungal species is their ability to survive inside macrophages and escape from these immune cells. In this review, we discuss the mechanisms behind intracellular survival and elaborate how escape is mediated by lytic and non-lytic pathways as well as strategies to induce programmed host cell death. We also discuss persistence as an alternative to rapid host cell exit. In the end, we address the consequences of fungal escape for the host immune response and provide future perspectives for research and development of targeted therapies.

"Under Pressure" - How fungi evade, exploit, and modulate cells of the innate immune system.

The human immune system uses an arsenal of effector mechanisms to prevent and counteract infections. Yet, some fungal species are extremely successful as human pathogens, which can be attributed to a wide variety of strategies by which these fungi evade, exploit, and modulate the immune system. These fungal pathogens normally are either harmless commensals or environmental fungi. In this review we discuss how commensalism, but also life in an environmental niche without human contact, can drive the evolution of diverse and specialized immune evasion mechanisms. Correspondingly, we discuss the mechanisms contributing to the ability of these fungi to cause superficial to life-threatening infections.

Evaluation of sexual function in females with exstrophy-epispadias-complex: A survey of the multicenter German CURE-Net.

OBJECTIVE: Standardized knowledge about genital function in adult female individuals with exstrophy-epispadias complex (EEC) is scarce. The aim of this study was to investigate sexual function using the standardized Female Sexual Function Index (FSFI), and to assess the influence of bladder and vaginal reconstruction and the presence of incontinence on FSFI results. METHOD: Sixty-one females (aged ≥18 years) recruited by the German multicenter network for congenital uro-rectal malformations (CURE-Net) were asked to complete the FSFI and a self-designed semi-structured questionnaire assessing comprehensive medical data, gynecological, and psychosocial items. Twenty-one eligible females (34%) returned both questionnaires (mean ± standard deviation [SD] age of 26 ± 5.1 years). RESULTS: In 43% of participants, a staged or single-staged approach had been used for reconstruction, and these had their bladder in use. A primary or secondary urinary diversion (UD) after cystectomy had been performed in 38% of participants. Of the participants, 57% lived in a committed partnership, and 62% had sexual intercourse on a regular basis, with a further 19% experiencing pain or discomfort thereby. Introitus plasty was done in 43%. Mean total FSFI for all participants was 21.3 (SD 1.9). Most domain scores of patients after introitus plasty were similar compared with those without an operative vaginal approach, except for satisfaction (p = 0.057) and pain (p = 0.024). Comparing incontinent with continent patients, significant differences were found for desire (mean 4.6 vs. 3.5, p = 0.021), lubrication (mean 3.1 vs. 4.2, p = 0.049), and satisfaction (mean 1.6 vs. 3.6, p = 0.0065). In contrast pain was not significant between groups. CONCLUSIONS: Sexual activity rate in the present study was similar to that reported in the literature (81% vs. 89%), whereas dyspareunia rate was lower in our cohort (19% vs. 24%). The risk for sexual dysfunction seems to be lower in patients reconstructed with primary or secondary UD than patients with bladder in use. It is surprising that lubrification was better after UD than after bladder neck surgery. Incontinence and in some parts the history of an introitus plasty may play an additional role in development of sexual dysfunction in EEC. Although most of the female EEC patients lived in a committed partnership and had sexual intercourse, total FSFI values <26.55 clearly indicate a risk of sexual dysfunction. Although continence itself played a major role, females reconstructed with UD seem to have better sexual function. Further evaluation of sexual outcome and improvement of care for these patients is mandatory.

Severe hyperlactatemia, lactate clearance and mortality in unselected critically ill patients.

PURPOSE: Hyperlactatemia may occur for a variety of reasons and is a predictor of poor clinical outcome. However, only limited data are available on the underlying causes of hyperlactatemia and the mortality rates associated with severe hyperlactatemia in critically ill patients. We therefore aimed to evaluate the etiology of severe hyperlactatemia (defined as a lactate level >10 mmol/L) in a large cohort of unselected ICU patients. We also aimed to evaluate the association between severe hyperlactatemia and lactate clearance with ICU mortality. METHODS: In this retrospective, observational study at an University hospital department with 11 ICUs during the study period between 1 April 2011 and 28 February 2013, we screened 14,040 ICU patients for severe hyperlactatemia (lactate >10 mmol/L). RESULTS: Overall mortality in the 14,040 ICU patients was 9.8 %. Of these, 400 patients had severe hyperlactatemia and ICU mortality in this group was 78.2 %. Hyperlactatemia was associated with death in the ICU [odds ratio 1.35 (95 % CI 1.23; 1.49; p < 0.001)]. The main etiology for severe hyperlactatemia was sepsis (34.0 %), followed by cardiogenic shock (19.3 %), and cardiopulmonary resuscitation (13.8 %). Patients developing severe hyperlactatemia >24 h of ICU treatment had a significantly higher ICU mortality (89.1 %, 155 of 174 patients) than patients developing severe hyperlactatemia ≤ 24 h of ICU treatment (69.9 %, 158 of 226 patients; p < 0.0001). Lactate clearance after 12 h showed a receiver-operating-characteristics area under the curve (ROC-AUC) value of 0.91 to predict ICU mortality (cut-off showing highest sensitivity and specifity was a 12 h lactate clearance of 32.8 %, Youden Index 0.72). In 268 patients having a 12-h lactate clearance <32.8 % ICU mortality was 96.6 %. CONCLUSIONS: Severe hyperlactatemia (>10 mmol/L) is associated with extremely high ICU mortality especially when there is no marked lactate clearance within 12 h. In such situations, the benefit of continued ICU therapy should be evaluated.