ABSTRACT
BACKGROUND: Surgical antimicrobial prophylaxis (SAP) is one of the major purposes of antimicrobial use. AIM: To determine the adherence to the Japanese SAP guidelines in Japanese university hospitals. METHODS: This was a retrospective cohort study including 15 general hospitals and one dental university hospital. Up to three cases of 18 designated surgeries were evaluated regarding adherence to Japanese SAP guidelines: selection of antibiotics, timing of administration, re-dosing intervals, and duration of SAP. When all items were appropriate, surgery was defined as 'appropriate'. FINDINGS: In total, 688 cases (22-45 cases per surgery) were included. The overall appropriateness was 46.8% (322/688), and the appropriateness of each surgery ranged from 8.0% (2/25, cardiac implantable electronic device implantation) to 92.1% (35/38, distal gastrectomy). The appropriateness of each item was as follows: pre/intraoperative selections, 78.5% (540/688); timing of administrations, 96.0% (630/656); re-dosing intervals, 91.6% (601/656); postoperative selection, 78.9% (543/688); and duration of SAP, 61.4% (423/688). The overall appropriateness of hospitals ranged from 17.6% (9/51) to 73.3% (33/45). The common reasons for inappropriateness were the longer duration (38.5%, 265/688) and choice of antibiotics with a non-optimal antimicrobial spectrum before/during, and after surgery (19.0%, 131/688 and 16.9%, 116/688, respectively), compared to the guideline. CONCLUSIONS: Adherence to the guidelines differed greatly between the surgeries and hospitals. Large-scale multi-centre surveillance of SAP in Japanese hospitals is necessary to identify inappropriate surgeries, factors related to the appropriateness, and incidences of surgical site infections.
Subject(s)
Anti-Infective Agents , Antibiotic Prophylaxis , Humans , Retrospective Studies , Hospitals, University , Japan , Guideline Adherence , Anti-Bacterial Agents/therapeutic use , Surgical Wound Infection/epidemiology , Surgical Wound Infection/prevention & control , Surgical Wound Infection/drug therapy , Anti-Infective Agents/therapeutic useABSTRACT
Immunomodulatory drugs (IMiDs) are effective therapeutic agents with direct inhibitory effects on malignant B- and plasma-cells and immunomodulatory effects on the T-cell activation. This dual function of IMiDs makes them appealing candidates for combination with a cancer vaccine. We investigated the immune stimulatory effects of lenalidomide, administrated to mice in doses, which provided comparable pharmacokinetics to human patients, on the potency of a novel fusion DNA lymphoma vaccine. The combination was curative in the majority of mice with 8d pre-established syngeneic A20 lymphomas compared with vaccine or lenalidomide alone and induced immune memory. In vivo depletion experiments established the requirement for effector CD8(+) and CD4(+) T cells in protective immunity. Unexpectedly, lenalidomide alone was also associated with reduced numbers of systemic myeloid-derived suppressor cell (MDSC) and regulatory T cell (Treg) in tumor-bearing but not naïve mice, an effect that was independent of simple tumor burden reduction. These results confirm and extend results from other models describing the effect of lenalidomide on enhancing T-cell immunity, highlight the potency of this effect, and provide a rationale for clinical application. Independently, a novel mechanism of action reversing tumor-induced immune suppression by MDSC is suggested.
Subject(s)
Cancer Vaccines/immunology , Immunologic Factors/pharmacology , Lymphoma/immunology , Lymphoma/pathology , Thalidomide/analogs & derivatives , Animals , Antibodies/immunology , Antibody Specificity/immunology , Antineoplastic Agents/pharmacology , Disease Models, Animal , Female , Humans , Immunologic Memory , Lenalidomide , Lymphoma/mortality , Lymphoma/therapy , Mice , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism , Thalidomide/pharmacology , Tumor Burden/drug effects , Tumor Burden/immunologyABSTRACT
Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic disorders characterized by normal or hypercellular but dysfunctional bone marrow. They usually are refractory to empirical therapeutic regimens. Recently the prevalence of MDS in the elderly is increasing and now the syndromes are relatively commonly encountered in elderly patients. Two major causes of death in MDS are progression to acute leukemia (especially in subtypes of RAEB and RAEB in T), and bone marrow aplasia. Since cytoreductive therapy for RAEB or RAEB in T in the elderly is often accompanied by serious adverse complications, such as infection and hemorrhage, special care is necessary. Here we describe successful induction remission in a 74-year-old man with MDS (RAEB in T) by twice daily low-dose cytosine arabinoside injections (10 mg/m2, s.c.), which was well-tolerated, free of serious adverse effects, and seemed to be a useful therapeutic option for elderly patient with RAEB or RAEB in T.
