Einfluss der präoperativen biliären Drainage auf die Rate an Gallenwegsinfektionen mit resistenten Mikroorganismen und deren Einfluss auf die postoperative Morbidität und Mortalität

Ziel dieser Dissertation war es zu untersuchen inwieweit eine präoperative biliäre Drainage (PBD) zu einer Gallenwegsinfektion mit resistenten Keimen führt, sowie in welchem Maße eine Gallenwegsinfektion mit resistenten Keimen die postoperative Morbidität und Mortalität nach Duodenopankreatektomie beeinflusst. Die PBD führte zu einer signifikant erhöhten mikrobiellen Gallenwegsinfektionsrate und zu einer signifikant erhöhten Polyinfektionsrate der Gallenwege. In der Resistenzanalyse zeigte sich, dass MRSA und E. faecium (multiresistente Erreger; MRE) die höchsten Resistenzraten aufwiesen und häufiger bei Patienten mit PBD gefunden wurden. Patienten mit MRE in den Gallenwegen hatten eine signifikant erhöhte postoperative Gesamtmorbidität, infektiöse Komplikationsrate und Wundinfektionsrate. Eine, aufgrund einer präoperativ bestehenden Cholangitis, durchgeführte Antibiotikatherapie sowie Langzeitstenting hatten einen wesentlichen Einfluss auf die Gallenwegsinfektionsrate

Hidradenitis suppurativa/Acne inversa in der Genitoanalregion

Die Hidradenitis suppurativa/Acne inversa (HS/AI) ist eine chronisch rezidivierende inflammatorische Hauterkrankung. Erhebungen zeigen, dass bevorzugt Männer einen perianalen, perinealen und glutealen Befall aufweisen, wohingegen bei Frauen die Axillen sowie die submammäre und inguinale Region vermehrt betroffen sind. Der Befall der Genitoanalregion ist mit einer stärkeren Einschränkung der Lebensqualität und einer größeren Belastung der sexuellen Gesundheit assoziiert als andere Lokalisationen. Darüber hinaus kann die HS/AI in der Genitoanalregion zu schwerwiegenden Komplikationen führen. Die perianale Fistelbildung, das pubogenitale Lymphödem und das Plattenepithelkarzinom zählen zu den 3 schwersten Komplikationen, deren Kenntnis entscheidend für ein adäquates Therapiemanagement ist.Hidradenitis suppurativa/acne inversa (HS/AI) is a chronic inflammatory skin disease. Several studies showed that perianal, perineal and gluteal involvement is more common in men. Axillary, submammary and inguinal localizations seem to be more prevalent in women. Involvement of the genitoanal region is associated with a higher reduced quality of live and sexual health compared to other locations. Moreover HS/AI in the genitoanal region can lead to serious complications. The knowledge of perianal fistula formation, pubogenital lymphedema and squamous cell carcinoma, which are three of the most severe complications, is critical for adequate treatment

Microbial profile and antimicrobial susceptibility of bacteria found in inflammatory hidradenitis suppurativa lesions

$\textit {Background:}$ The role of bacterial colonization in hidradenitis suppurativa (HS) lesions is poorly understood. To date, data on the related microbial profile and especially on bacterial resistance rates are scarce. $\textit {Methods:}$ The results of bacterial cultures and susceptibility patterns of the isolated microorganisms obtained from deep portions of HS lesions from patients who underwent surgery at our HS Centre between 2010 and 2015 were retrospectively evaluated. $\textit {Results:}$ Analyses of 113 bacterial samples from 113 HS patients revealed bacterial growth in 95 samples (84.1%). Polymicrobial growth was found in 51 samples (45.1%). Coagulase-negative $\it staphylococci$ and $\textit {Staphylococcus aureus}$ were the most commonly isolated bacteria, followed by $\textit {Proteus mirabilis}$ and $\textit {Escherichia coli}$. Data on susceptibility testing were available for 68 samples, which yielded 129 isolates. The isolated strains were primarily resistant to penicillin G, followed by erythromycin, clindamycin and ampicillin. The highest effectiveness against isolates was observed for fosfomycin, imipenem, fluoroquinolones (moxifloxacin, ciprofloxacin, levofloxacin), and cotrimoxazole. $\textit {Conclusions:}$ Our findings on bacterial species and their topographical distribution revealed that the microbial flora in HS lesions reflects commensal flora of the skin. Due to the susceptibility rate and immunomodulatory and anti-inflammatory properties, cotrimoxazole may represent an alternative antibiotic agent and should be considered for therapy in HS patients

Increased expression profile of NCSTN, Notch and PI3K/AKT3 in hidradenitis suppurativa

$\bf Background$ In a small number of kindreds with familial hidradenitis suppurativa (HS) different mutations of NCSTN (nicastrin) have been identified. Blocking of NCSTN leads to impairment of the Notch and PI3K/AKT signalling pathway, which is assumed to play a pathogenic role in HS. However, very limited data are available concerning expression levels of these pathway components in HS skin. $\bf Objectives$ To analyse the mRNA and protein expression of NCSTN, Notch1–3, PIK3R3 and AKT3 in HS. $\bf Methods$ Skin samples from healthy controls, lesional and perilesional skin of HS patients with and without a positive family history were analysed by quantitative real-time RT-PCR and immunohistochemistry. Univariate statistical analyses were conducted regarding association between expression levels and patient's characteristics. $\bf Results$ Expression levels of all investigated genes showed significantly higher levels in lesional HS skin compared with healthy controls. Univariate analysis showed no association between a positive family history and mRNA expression levels. Perilesional HS skin of patients with mild disease severity (Hurley I) showed significant higher mRNA expression levels of the investigated pathway components compared to moderate (Hurley II) and severe disease (Hurley III). $\bf Conclusion$ We found no evidence for diminished expression levels of the Notch signalling. In contrast, the NCSTN, Notch and PI3K/AKT signalling components are overexpressed in HS. Future research is needed to investigate a possible pathogenetic role or to reveal a coactivation of these overexpressed components during inflammatory response in HS

Altered global 5-hydroxymethylation status in hidradenitis suppurativa

$\it Background:$ The pathogenesis of hidradenitis suppurativa (HS), with its complex inflammatory network, is still elusive. Imbalances in DNA methylation can lead to genome destabilization and have been assumed to play a role in inflammatory diseases. Global DNA methylation and hydroxymethylation have not been studied in HS yet. $\it Objective:$ We conducted this study to investigate the global DNA methylation and hydroxymethylation status in lesional and perilesional HS skin compared to healthy controls. $\it Methods:$ Immunohistochemical analysis was performed for 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) in 30 lesional and 30 corresponding healthy-appearing perilesional HS tissue samples. We included 30 healthy subjects as an interindividual control group. $\it Results:$ 5-hmC levels were significantly lower in healthy-appearing perilesional ($\it {p}$ < 0.0001) and lesional HS skin ($\it {p}$ < 0.0001) when compared to healthy controls. There was no significant difference between lesional HS skin and perilesional HS skin regarding 5-hmC levels ($\it {p}$ = 0.6654). In contrast to 5-hmC, 5-mC staining showed no significant changes between the 3 groups. Univariate analysis revealed no significant association between patients’ characteristics, disease severity, and the levels of 5-mC and 5-hmC. $\it Conclusion:$ Our findings indicate that imbalances in DNA hydroxymethylation may play a role in the pathogenesis of HS rather than DNA methylation. Further studies are warranted to investigate the significance of DNA hydroxymethylation and the regulating enzymes in HS in order to advance our knowledge of the inflammatory network in this disease