[Liver disease in systemic Lupus erythematodes - results of an explorative observational study]. / Hepatopathie bei systemischem Lupus erythematodes ­ Ergebnisse einer explorativen Beobachtungsstudie.

INTRODUCTION: Systemic lupus erythematodes (SLE) represents an autoimmune disease with a highly variable clinical course affecting numerous organs. Hepatic manifestation seems to be rare. It is not clear whether hepatic disease in SLE is of any prognostic importance or whether it correlates with disease activity. METHODS: Our patient cohort included 172 patients with proven SLE, all treated at Bogenhausen Hospital between 01.2009 and 12.2015. Retrospectively, all admissions as inpatients and outpatients were analyzed (n = 671; mean 3.9 per patient). Liver damage was diagnosed by evaluation of laboratory parameters on the basis of pathological liver enzymes and by imaging methods. Disease activity of SLE was calculated by using European Consensus Lupus Activity Measurement-(ECLAM-)Score. Additionally, parameters of SLE including disease duration, organ damage and immune suppressive medication and their possible association with hepatopathy were analyzed. RESULTS: Elevated liver parameters (ASAT, ALAT, GGT, AP) indicating liver damage were detectable in 109 patients (63.4 % of total population) demonstrating significant association with disease activity (on the basis of ECLAM-score, p < 0.001), duration of treatment, frequency of admissions (p < 0.01, respectively), number of used immunosuppressive agents (p < 0.018), increased blood sedimentation rate (p < 0.001) and reduction of serum complement (p < 0.03). Abnormal ultrasound findings of the liver (e. g., non-alcoholic fatty liver disease) were diagnosed in 19.8 %. DISCUSSION: Elevated liver parameters occur frequently in patients with SLE, especially in context with increased disease activity (on the basis of ECLAM-Score or intensified immunosuppressive therapy) and prolonged course of the disease. Liver enzymes should be obtained regularly in patients with SLE and, if necessary, further diagnostic steps should be initiated. Further prospective studies might clarify whether abnormal liver parameters must be included in activity indices to judge disease activity in SLE.

Olfactory Function is Affected in Patients with Cirrhosis Depending on the Severity of Hepatic Encephalopathy.

INTRODUCTION AND AIM: Olfactory functions are altered to a variable degree by chronic liver disease. Few studies including only small populations of patients emphasized the possibility of hepatic encephalopathy (HE) influencing olfactory nervous tasks. So far, no study has explicitly focused on olfactory function depending on the severity of HE as assessed by objective diagnostic procedures. Thus we performed a study using the "Sniffin' Sticks" test system, critical flicker-fusion frequency (CFF) and clinical West Haven criteria. MATERIAL AND METHODS: 54 cirrhotic patients with liver cirrhosis were included. Furthermore, 43 adult volunteers participating as a non-cirrhotic control group. Olfactory testing was performed using the "Sniffin' Stick" test battery (Burghart Medizintechnik, Wedel, Germany) which renders a widely-used tool both in clinical and research settings for the assessment of olfactory threshold, odor identification and discrimination. Several complications of cirrhosis were diagnosed by reference methods. Statistical analysis of cirrhosis-associated complications and their relation to olfactory function was performed. Assessment of HE and classification of different stages were performed according to clinical criteria (West- Haven criteria) and according to CFF, which was determined using a portable analyzer. RESULTS: Olfactory function was significantly reduced in cirrhotic patients (in 61.1%) compared to controls (p < 0.001). Among cirrhotics patients, the prevalence of olfactory deficits (hyposmia, anosmia) increased with the severity of HE as assessed by CFF and clinical criteria (p = 0.008 and p = 0.097, respectively). No correlation was observed between olfactory deficits and severity of liver disease as assessed by Child-Pugh-Score, etiology of cirrhosis and complications of cirrhosis such as ascites and portal venous hypertension. CONCLUSIONS: Olfactory testing serves as a screening tool for HE and may facilitate grading of HE-severity.

Seventy-two Cycles of FOLFIRINOX: Long Term Treatment in a Patient with Metastatic Adenocarcinoma of the Pancreatic Tail.

CONTEXT: Pancreatic adenocarcinoma is one of the most lethal malignancies worldwide. In patients with unresectable tumor there are several strategies of palliative chemotherapy, either gemcitabine based regimens or FOLFIRINOX, which is supposed to be most efficient but also most toxic. Hence, management of toxicity is crucial to perform a therapy consisting of FOLFIRINOX. CASE REPORT: We report on a 69-year-old female patient suffering from adenocarcinoma of the pancreatic tail with multiple liver metastases. Palliative chemotherapy comprising leucovorin, fluorouracil, oxaliplatin and irinotecan (FOLFIRINOX) was initiated in February 2011 and was tolerated very well. Subsequent computed tomography-scans showed significant reduction of the tumor load in the liver as well as in the primary pancreatic tumor. The serum levels of the tumor marker CA 19-9 were elevated initially and decreased concomitantly. Thus, chemotherapy was continued for more than 3 years, and up to 72 cycles were administered until April 2014. Due to intermittent neutropenia and mucositis the initial dose was reduced to 60% of the calculated standard dose. In April 2014, an intermediate staging by computed tomography and FDG-PET revealed significant reduction of the size of the primary pancreatic tumor compared with February 2011. Liver metastases could hardly be detected anymore. After pausing chemotherapy for 12 weeks, one liver metastasis reappeared and was treated by RFA in August 2014. Meanwhile, in October 2014 there is no radiological evidence on any existing tumor or metastasis. CONCLUSION: Our report demonstrates that a sufficient tolerance of chemotherapy with FOLFIRINOX is achievable, what makes a long term treatment with FOLFIRINOX feasible and can lead to impressive results.

Contribution of trimeric autotransporter C-terminal domains of oligomeric coiled-coil adhesin (Oca) family members YadA, UspA1, EibA, and Hia to translocation of the YadA passenger domain and virulence of Yersinia enterocolitica.

The Oca family is a novel class of autotransporter-adhesins with highest structural similarity in their C-terminal transmembrane region, which supposedly builds a beta-barrel pore in the outer membrane (OM). The prototype of the Oca family is YadA, an adhesin of Yersinia enterocolitica and Yersinia pseudotuberculosis. YadA forms a homotrimeric lollipop-like structure on the bacterial surface. The C-terminal regions of three YadA monomers form a barrel in the OM and translocate the trimeric N-terminal passenger domain, consisting of stalk, neck, and head region to the exterior. To elucidate the structural and functional role of the C-terminal translocator domain (TLD) and to assess its promiscuous capability with respect to transport of related passenger domains, we constructed chimeric YadA proteins, which consist of the N-terminal YadA passenger domain and C-terminal TLDs of Oca family members UspA1 (Moraxella catarrhalis), EibA (Escherichia coli), and Hia (Haemophilus influenzae). These constructs were expressed in Y. enterocolitica and compared for OM localization, surface exposure, oligomerization, adhesion properties, serum resistance, and mouse virulence. We demonstrate that all chimeric YadA proteins translocated the YadA passenger domain across the OM. Y. enterocolitica strains producing YadA chimeras or wild-type YadA showed comparable binding to collagen and epithelial cells. However, strains producing YadA chimeras were attenuated in serum resistance and mouse virulence. These results demonstrate for the first time that TLDs of Oca proteins of different origin are efficient translocators of the YadA passenger domain and that the cognate TLD of YadA is essential for bacterial survival in human serum and mouse virulence.