Skin infections due to Panton-Valentine leukocidin (PVL)-producing S. aureus-Cost effectiveness of outpatient treatment.

INTRODUCTION: Skin and soft tissue infections (SSTI) caused by Panton-Valentine leukocidin (PVL)-producing strains of Staphylococcus aureus (PVL-SA) are associated with recurrent skin abscesses. Secondary prevention, in conjunction with primary treatment of the infection, focuses on topical decolonization. Topical decolonization is a standard procedure in cases of recurrent PVL-SA skin infections and is recommended in international guidelines. However, this outpatient treatment is often not fully reimbursed by health insurance providers, which may interfere with successful PVL-SA decolonization. AIM: Our goal was to estimate the cost effectiveness of outpatient decolonization of patients with recurrent PVL-SA skin infections. We calculated the average cost of treatment for PVL-SA per outpatient decolonization procedure as well as per in-hospital stay. METHODS: The study was conducted between 2014 and 2018 at a German tertiary care university hospital. The cohort analyzed was obtained from the hospital's microbiology laboratory database. Data on medical costs, DRG-based diagnoses, and ICD-10 patient data was obtained from the hospital's financial controlling department. We calculated the average cost of treatment for patients admitted for treatment of PVL-SA induced skin infections. The cost of outpatient treatment is based on the German regulations of drug prices for prescription drugs. RESULTS: We analyzed a total of n = 466 swabs from n = 411 patients with recurrent skin infections suspected of carrying PVL-SA. PVL-SA was detected in 61.3% of all patients included in the study. Of those isolates, 80.6% were methicillin-susceptible, 19.4% methicillin-resistant. 89.8% of all patients were treated as outpatients. In 73.0% of inpatients colonized with PVL-SA the main diagnosis was SSTI. The median length of stay was 5.5 days for inpatients colonized with PVL-SA whose main diagnosis SSTI; the average cost was €2,283. The estimated costs per decolonization procedure in outpatients ranged from €50-€110, depending on the products used. CONCLUSION: Our data shows that outpatient decolonization offers a highly cost-effective secondary prevention strategy, which may prevent costly inpatient treatments. Therefore, health insurance companies should consider providing coverage of outpatient treatment of recurrent PVL-SA skin and soft tissue infections.

Ontogenetic allometry constrains cranial shape of the head-first burrowing worm lizard Cynisca leucura (Squamata: Amphisbaenidae).

Amphisbaenians are fossorial, predominantly limbless squamate reptiles with distinct cranial shapes corresponding to specific burrowing behaviors. Due to their cryptic lifestyles and the scarcity of museum specimens, little is known of their intraspecific variation, particularly regarding cranial osteology. This represents a critical lack of information, because the majority of morphological investigations of squamate relationships are based on cranial characters. We investigated cranial variation in the West African Coast Worm Lizard Cynisca leucura, a round-headed member of the Amphisbaenidae. Using geometric morphometric analyses of three-dimensional computed tomographic scans, we found that cranial osteology of C. leucura is highly conserved, with the majority of shape changes occurring during growth as the cranium becomes more slender and elongate, accompanied by increasing interdigitation among the dermal roofing bones. Elements of the ventral portion of the cranium remain loosely connected in adults, possibly as a protective mechanism against repeated compression and torsion during burrow excavation. Intraspecific variation was strongly correlated with size change from juveniles to adults, indicating a dominant role of ontogenetic allometry in determining cranial shape. We found no evidence of sexual dimorphism, either during growth or among adults. Given the fossorial habits of C. leucura, we hypothesize that cranial allometry is under strong stabilizing selection to maintain adequate proportions for head-first digging, thereby constraining the ability of individuals to respond to differing selection pressures, including sexual selection and variation in diet or microhabitat. For species in which digging imposes less mechanical stress (e.g., in softer sand), allometric associations during growth may be weakened, allowing changes to the ontogenetic trajectory and subsequent morphological traits. Such developmental dissociation between size and shape, known as heterochrony, may also be implicit in the evolution of the other amphisbaenian cranial shapes (shovel, spade, and keel), which may themselves be functionally adapted for their respective burrowing techniques. J. Morphol. 277:1159-1167, 2016. © 2016 Wiley Periodicals, Inc.

The Role of Regulatory CD4 T Cells in Maintaining Tolerance in a Mouse Model of Autoimmune Hepatitis.

BACKGROUND: The role of regulatory CD4 T cells (Treg) in immune-mediated liver disease is still under debate. It remains disputed whether Treg suppress T cell-mediated hepatitis in vivo and whether hepatic regulatory T cells are functional in patients with autoimmune hepatitis. METHODS: We used TF-OVA mice, which express ovalbumin in hepatocytes, to investigate the impact of Treg in a model of autoimmune hepatitis. Treg isolated from inflamed livers of TF-OVA mice were tested for their functionality in vitro. By employing double transgenic TF-OVAxDEREG (DEpletion of REGulatory T cells) mice we analyzed whether Treg-depletion aggravates autoimmune inflammation in the liver in vivo. RESULTS: CD25+Foxp3+ CD4 T cells accumulated in the liver in the course of CD8 T cell-mediated hepatitis. Treg isolated from inflamed livers were functional to suppress CD8 T-cell proliferation in vitro. Depletion of Treg in TF-OVAxDEREG mice dramatically amplified T cell-mediated hepatitis. Repeated administration of antigen-specific CD8 T cells led to a second wave of inflammation only after depletion of Treg. CONCLUSION: Our data add to the evidence for an important role of Treg in autoimmune hepatitis and show that Treg reduce the severity of T-cell mediated hepatitis in vivo. They constitute a key immune cell population that actively maintains a tolerogenic milieu in the liver and protects the liver against repeated inflammatory challenges.