First report of Salmonella 1,4,[5],12:i:- in free-ranging striped dolphins (Stenella coeruleoalba), Italy.

Between 2015 and the beginning of 2018 (January-March), 30 cetaceans were found stranded along the Ligurian Sea coast of Italy. Necropsies were performed in 22 cases and infectious diseases resulted the most common cause of death. Three striped dolphins, showed a severe coinfection involving the monophasic variant of Salmonella Typhimurium (Salmonella 1,4,[5],12:i:-). The isolates were characterized based on antimicrobial resistance, Multiple-Locus Variable-number tandem-repeat Analysis (MLVA) and whole-genome sequencing (WGS). All isolates demonstrated the same multidrug resistant genotype (ASSuT isolates), showed three different MLVA profiles, two of which closely related, and were identified as Sequence Type 34. Moreover, Single nucleotide polymorphisms (SNP) analysis confirmed strong correlations between two out of the three isolates. To our knowledge, S. 1,4,[5],12:i:-, one of the most common serovars in cases of human infection and food sources worldwide, has not previously been described in marine mammals, and reports of Salmonella-associated disease in free-ranging cetaceans are rare. These results highlight the role of cetaceans as sentinel species for zoonotic and terrestrial pathogens in the marine environment, suggest a potential risk for cetaceans and public health along the North Western Italian coastline and indicate cetaceans as a novel potential reservoir for one of the most widespread Salmonella serovars.

High rate of colistin resistance among patients with carbapenem-resistant Klebsiella pneumoniae infection accounts for an excess of mortality.

Carbapenem-resistant Klebsiella pneumoniae (CR-KP) is becoming a common cause of healthcare-associated infection in Italy, with high morbidity and mortality. Prevalent CR-KP clones and resistance mechanisms vary between regions and over time. Therapeutic approaches and their impact on mortality have to be investigated. We performed a prospective study of patients with CR-KP isolation, hospitalized in nine hospitals of Rome, Italy, from December 2010 to May 2011, to describe the molecular epidemiology, antibiotic treatment and risk factors for mortality. Overall, 97 patients (60% male, median age 69 years) were enrolled. Strains producing blaKPC-3 were identified in 89 patients, blaVIM in three patients and blaCTX-M-15 plus porin defects in the remaining five patients. Inter-hospital spread of two major clones, ST512 and ST258, was found. Overall, 36.1% and 20.4% of strains were also resistant to colistin and tigecycline, respectively. Infection was diagnosed in 91 patients who received appropriate antibiotic treatment, combination therapy and removal of the infectious source in 73.6%, 59.3% and 28.5% of cases, respectively. Overall, 23 different antibiotic regimens were prescribed. In-hospital mortality was 25.8%. Multivariate analysis adjusted for appropriate treatment, combination therapy and infectious-source removal, showed that Charlson comorbidity score, intensive-care unit onset of infection, bacteraemia and infection due to a colistin-resistant CR-KP strain were independent risk factors for mortality. The spread of clones producing K. pneumoniae carbapenemases, mainly ST258, is currently the major cause of CR-KP infection in central Italy. We observed a high rate of resistance to colistin that is independently associated with worse outcome.

Epidemic multidrug-resistant Acinetobacter baumannii related to European clonal types I and II in Rome (Italy).

The molecular epidemiology and the genetic basis of antibiotic resistance in 88 multidrug-resistant (MDR) Acinetobacter baumannii strains isolated during 18 months from infected patients in seven intensive care units (ICUs) in Rome were investigated. Random amplified polymorphic DNA and macrorestriction analysis identified two predominant clonal types, genetically related to the European epidemic clones I (type 2) and II (type 1), accounting for 98.9% of A. baumannii ICU isolates. Type 1 was isolated from all ICUs under survey. Class 1 integrons of 2.2 and 2.5 kb were detected in type 1 and type 2 isolates, respectively. The integron structures were similar to those previously determined for epidemic A. baumannii strains from various European countries, and suggestive of integron rearrangement/exchange among isolates related to the European epidemic clones I and II. Carbapenem resistance was associated with the presence of the bla(OXA-58) gene in type 1 isolates. The results indicate that the A. baumannii type 1 clone has a high potential of spreading among hospitals.

Activity of endovesical gemcitabine in BCG-refractory bladder cancer patients: a translational study.

Intravesical gemcitabine (Gem) has shown promising activity against transitional cell carcinomas (TCC) of the bladder, with moderate urinary toxicity and low systemic absorption. The present phase II study evaluated the activity of biweekly intravesical treatment with Gem using a scheme directly derived from in vitro preclinical studies. Patients with Bacille Calmette-Guérin (BCG) -refractory Ta G3, T1 G1-3 TCC underwent transurethral bladder resection and then intravesical instillation with 2000 mg Gem diluted in 50 ml saline solution on days 1 and 3 for 6 consecutive weeks. Thirty-eight (95%) of the 40 patients showed persistent negative post-treatment cystoscopy and cytology 6 months after Gem treatment, while the remaining 2 patients relapsed at 5 and 6 months. At a median follow-up of 28 months, recurrences had occurred in 14 patients. Among these, four had downstaged (T) disease, three had a lower grade (G) lesion and three had a reduction in both T and G. Urinary and systemic toxicity was very low, with no alterations in biochemical profiles. In conclusion, biweekly instillation of Gem proved active in BCG-refractory Ta G3, T1 G1-3 TCC. Our results highlight the importance of preclinical studies using in vitro systems that adequately reproduce the conditions of intravesical clinical treatment to define the best therapeutic schedule.

Second-line high-dose chemotherapy in patients with mediastinal and retroperitoneal primary non-seminomatous germ cell tumors: the EBMT experience.

BACKGROUND: Results of second-line chemotherapy in patients with extragonadal non-seminomatous germ cell tumor (NSGCT) appear inferior to results in testicular NSGCT. Patients with retroperitoneal NSGCT achieve a comparable long-term survival rate of 30%, but the salvage rates of patients with mediastinal primary are less than 10%. We conducted a retrospective analysis on patients with mediastinal and retroperitoneal NSGCT treated with second-line high-dose chemotherapy (HDCT) registered with the European Group for Blood and Marrow Transplantation (EBMT). PATIENTS AND METHODS: Between 1987 and 1999, 59 registered patients with retroperitoneal (n=37) and mediastinal (n=22) primary NSGCT, median age 28 years (range 18-60), were treated with second-line HDCT. All had received cisplatin-containing chemotherapy as first-line treatment. RESULTS: Toxic death occurred in three cases (5%). With a median follow-up of 58 months (range 14-114), 18/59 patients (30%) continue to be disease-free. Of three patients who had a disease recurrence after HDCT, one patient achieved a disease-free status with further chemotherapy and surgery. In total, 19 patients (32%) are currently disease-free. Sixteen of 37 patients (43%) with retroperitoneal NSGCT, and three of 22 patients (14%) with mediastinal NSGCT are currently alive and disease-free. CONCLUSIONS: Second-line HDCT might represent a possible option for patients with retroperitoneal primary NSGCT. New salvage strategies are needed for patients with mediastinal NSGCT.

First-line high-dose chemotherapy for patients with poor prognosis extragonadal germ cell tumors: the experience of the European Bone Marrow Transplantation (EBMT) Solid Tumors Working Party.

Extragonadal germ cell tumors are classified according to the staging system of the International Germ Cell Cancer Collaborative Group (IGCCCG). The 5-year overall and disease-free survival rates for poor prognosis patients are 41 and 48%, respectively after standard-dose chemotherapy. We report the experience of the EBMT Solid Tumours Working Party (STWP) with first-line HDCT with hematopoietic progenitor cell support (HPCS) in patients with poor prognosis extragonadal nonseminomatous germ cell tumor (NSGCT). Between 1990 and 2001, 22 extragonadal NSGCT patients (21 M, 1 F), median age 30 years (range 17-52) were treated with first-line HDCT with HPCS. Primary site was mediastinum in 11 patients, retroperitoneum in 10, and unknown in one. The Carbopec regimen, consisting of high doses of carboplatin, etoposide, and cyclophosphamide, was used in most cases (12 patients). No treatment-related deaths occurred. No patient developed myelodysplasia or a secondary leukemia. In total, 17 of 22 patients (77%) achieved complete remission. At a median follow-up of 50 months (range 26-132), 15 patients (68%) are alive disease-free. The survival rates of patients with poor prognosis extragonadal NSGCT treated with first-line HDCT in the EBMT STWP experience appear higher than that expected according to the IGCCCG classification.

High-dose epirubicin, preceded by dexrazoxane, given in combination with paclitaxel plus filgrastim provides an effective mobilizing regimen to support three courses of high-dose dense chemotherapy in patients with high-risk stage II-IIIA breast cancer.

SUMMARY: We verified the possibility of collecting large amounts of peripheral blood stem cells (PBSCs) to support three courses of adjuvant high-dose dense chemotherapy (HDDC) with high-dose epirubicin, preceded by dexrazoxane, and high-dose paclitaxel, in patients with high-risk breast cancer (>/=9 positive nodes). The mobilizing regimen consisted of high-dose epirubicin 150 mg/m(2), preceded by dexrazoxane 1000 mg/m(2) (day 1), given in combination with paclitaxel 175 mg/m(2) (day 2), plus filgrastim. Of the 25 patients enrolled, one went off study due to a severe hypersensitivity reaction to paclitaxel, another did not undergo leukapheresis due to fever persistent after hematological recovery, while in 23 patients an adequate number of PBSCs was collected by a single leukapheresis. The median number of CD34+, CD34+/CD33-, and CD34+/CD38- cells collected per patient was 17 x 10(6)/kg, 13.4 x 10(6)/kg, and 1.5 x 10(6)/kg, respectively. Neutropenia was the only grade 4 toxicity and lasted a median of 3 days. High-dose epirubicin, preceded by dexrazoxane for the first time used in mobilizing regimen, and paclitaxel plus filgrastim are effective in releasing large amounts of PBSCs, which can then be safely employed to support multiple courses of HDDC.

[Cohen syndrome. A new case and review of the literature]. / Sindrome di Cohen. Un nuovo caso e revisione della letteratura.

We report the case of a 12-year-old child suffering from mild mental retardation, hypotonia, long hands with tapering fingers, microcephaly, truncal obesity, particular facial features. The association of these abnormalities has been known as Cohen Syndrome since 1973. Such a dysmorphic syndrome is usually inherited as an autosomal recessive trait whose gene has not been yet localized. There is no biological marker and the diagnosis is made only on a clinical basis. The diagnosis is quite difficult because of the intrafamiliar variation and the lack of a symptom present in 100% of the cases. From the analysis of the literature it proves that the more frequent symptoms are: mental retardation, open mouth, short philtrum, high palate, hypotonia. Because of the diagnostic difficulties it is possible that this syndrome was underestimate. Moreover, it is usually diagnosed too late, (mean age: 12,9). Therefore, we think necessary to consider the possibility of Cohen Syndrome in the case of every mental retardation of unknown cause.