Case report: Long-term follow-up of patients who received a FimCH vaccine for prevention of recurrent urinary tract infections caused by antibiotic resistant Enterobacteriaceae: a case report series.

Urinary tract infections (UTI) caused by carbapenem-resistant Enterobacteriaceae (CRE) are considered one of the most urgent health threats to humans according to the Centers for Disease Control (CDC), and the World Health Organization (WHO). A FimCH Vaccine expanded access study is being conducted in patients with a history of antibiotic resistant UTIs who are considered to be at risk for development of CRE UTI. This case series describes the clinical, safety and immunogenicity findings for four participants who received a FimCH four-vaccine series. Participants were followed for 12 months after administration of the fourth vaccine for safety, general health status and UTI occurrence. The study was later amended to allow additional follow-up of up to five years post vaccine administration to assess long-term health status, UTI occurrences and to obtain blood samples for anti-FimH antibody testing. In our population of 4 study participants, the number of symptomatic UTI occurrences caused by gram-negative bacteria in the 12-month period following peak anti-FimH antibody response were approximately 75% lower than the 12-month period preceding study enrollment. These results are consistent with the 30-patient cohort of a Phase 1 study with the same FimCH Vaccine. UTI occurrences increased during the long-term follow-up period for all 4 participants but did not reach the rate observed pre-vaccination. No new safety concerns related to the FimCH Vaccine were identified during long-term follow-up. This case series has clinical importance and public health relevance since it examines and reports on UTI frequency and recurrence following vaccination with the FimCH Vaccine in a high-risk population of patients with recurrent UTI. Additionally, participants described improved well-being following vaccination which was maintained in the long-term follow-up period.

Laparoscopic removal of extraosseous Ewing's sarcoma of the kidney in a pediatric patient.

In the pediatric population, to the best of our knowledge, only 2 cases of renal extraosseous Ewing's sarcoma/primitive neuroectodermal tumor (EES/PNET) have been published. We report the initial case of renal EES/PNET occurring in a 10-year-old girl treated by a laparoscopic radical nephrectomy. The regimen used is the first documented use of neoadjuvant chemotherapy prior to laparoscopic radical nephrectomy for PNET. This approach obviated the need for a large incision and a prolonged postsurgical recovery. The minimally invasive nature of the laparoscopic procedure allowed for a rapid convalescence and resumption of her chemotherapy regimen within 14 days of the surgery.

Ureteral pseudodiverticulum associated with absorbable suture clips after laparoscopic pyeloplasty: case report.

A 48 year-old woman with pyelonephritis was found to have bilateral ureteropelvic junction (UPJ) obstruction and a nonfunctioning right kidney. She initially underwent a laparoscopic left nondismembered pyeloplasty using absorbable polydioxanone Lapra-Ty suture clips (Ethicon Endosurgery, Cincinnati, OH) to secure the anastomosis. An antegrade endopyelotomy was later necessitated. Both procedures were complicated by postoperative bacteruria and funguria. She then underwent a laparoscopic dismembered pyeloplasty, again utilizing Lapra-Ty suture clips to secure the anastomosis. Postoperatively, her course was complicated by anastomotic extravasation, bacteriuria, and funguria. Subsequently, an antegrade nephrostogram revealed a 2.5-cm diverticulum just distal to the UPJ, which contained numerous 2- to 4-mm filling defects. Nephroscopic exploration of the pseudodiverticulum revealed numerous Lapra-Ty clips, which were basket extracted. The pseudodiverticulum was fulgurated with a holmium laser. She eventually had restricturing with recurrence of the pseudodiverticulum and was treated successfully by open ureterocalicostomy.

Insulin-like growth factor-I receptor activation blocks doxorubicin cytotoxicity in sarcoma cells.

More than 80% of patients with extremity sarcoma ultimately develop metastases to pulmonary sites. Doxorubicin alone or in combination with other chemotherapeutic agents may result in partial or complete tumor response for sarcoma pulmonary metastases. Regardless of the response, there has been no proven survival benefit from cytotoxic chemotherapy in the treatment of localized or metastatic soft tissue sarcoma. Insulin-like growth factor-I receptor (IGF-I-R) activation may contribute to resistance to chemotherapy in mesenchymal neoplasia. IGF-I-R activation by its ligand decreases in vitro cytotoxic response of sarcoma to doxorubicin, the most active agent against soft tissue sarcoma in adults. Furthermore, IGF-I-R is frequently overexpressed in soft tissue sarcoma and may predict poor response to traditional chemotherapy. The effect of doxorubicin on a human soft tissue sarcoma cell derived from a dedifferentiated lung metastasis was evaluated using titrated doxorubicin doses with and without exogenous IGF-I (100 ng/ml). Western blot analysis was performed to evaluate levels of phosphorylated IGF-I-R under control and experimental conditions. In vitro proliferation assays were performed. Nuclear activation through IGF-I receptor mediated pathways prior to exposing sarcoma cells to doxorubicin altered the pattern of response to doxorubicin with enhanced mitogenesis (>2-fold) and blunted doxorubicin cytotoxicity (>10% change in IC50). These data suggest that activation of IGF-I receptor in sarcoma cells is a potential mechanism for tumor resistance to doxorubicin. Inhibition of IGF-I receptor activation represents a novel approach to enhance the degree and duration of response to traditional chemotherapy against soft tissue sarcoma.