The endoscopic endonasal transsphenoidal approach has been proposed in the past decade as a minimally invasive surgical technique for the removal of pituitary tumors. From January 1997 to November 1999, 100 consecutive patients with pituitary tumors underwent endoscopic endonasal surgery, according to Jho's technique. We employed 0 degrees, 30 degrees, 45 degrees, and 70 degrees rigid endoscopes, 18 - 30 cm in length, 4 mm in diameter with an outer sleeve for irrigation and secured to a holder. Among the 87 pituitary adenomas, tumor removal was total in 51, subtotal (> 80 %) in 20 and partial in 16 cases. Four craniopharyngiomas were totally removed and an intra-suprasellar arachnoid cyst was emptied; a biopsy was performed in the two patients with a clivus chordoma. The two cases of sphenoid sinusitis were cured by surgery, the three patients with spontaneous CSF rhinorrhea were successfully treated and the residual nasal meningocele was removed. The endoscopic endonasal transsphenoidal approach appeared to be less traumatic than the traditional microsurgical approach, was very effective, and was characterized by a reduced number of complications. However, the relatively small series together with the short follow-up do not allow us to draw definitive conclusions. The post-operative reduction in hospital stay (two days in 40 of 100), significantly reduced the cost of patient's management.

BACKGROUND Addition of temozolomide (TMZ) to radiotherapy (RT) improves overall survival (OS) in glioblastoma, but previous studies suggest that patients with tumors harboring an unmethylated MGMT promoter derive minimal benefit. The aim of this open-label, phase 3 CheckMate 498 study was to evaluate the efficacy of nivolumab (NIVO)+RT compared with TMZ+RT in newly diagnosed glioblastoma with unmethylated MGMT promoter. METHODS Patients were randomized 1:1 to standard RT (60 Gy) + NIVO (240 mg every 2 weeks for 8 cycles, then 480 mg every 4 weeks) or RT+TMZ (75 mg/m 2 daily during RT and 150-200 mg/m 2/day 5/28 days during maintenance). The primary endpoint was OS. RESULTS A total of 560 patients were randomized, 280 to each arm. Median OS was 13.4 months (95% CI, 12.6-14.3) with NIVO+RT and 14.9 months (95% CI, 13.3-16.1) with TMZ+RT (hazard ratio [HR], 1.31; 95% CI, 1.09-1.58; P=0.0037). Median progression-free survival was 6.0 months (95% CI, 5.7-6.2) with NIVO+RT and 6.2 months (95% CI, 5.9-6.7) with TMZ+RT (HR, 1.38; 95% CI, 1.15-1.65). Response rates were 7.8% (9/116) with NIVO+RT and 7.2% (8/111) with TMZ+RT; grade 3/4 treatment-related adverse event (TRAE) rates were 21.9% and 25.1%, and any-grade serious TRAE rates were 17.3% and 7.6%, respectively. CONCLUSIONS The study did not meet the primary endpoint of improved OS; TMZ+RT demonstrated a longer median OS than NIVO+RT. No new safety signals were detected with NIVO in this study. The difference between the study treatment arms is consistent with the use of TMZ+RT as standard of care for glioblastoma.

Temozolomide is effective in some patients with progressive pituitary adenoma or carcinoma. We report a survey study of Italian patients treated with Temozolomide because of aggressive pituitary adenoma or carcinoma resistant to standard therapies. Italian endocrinologists were surveyed and asked to participate into the study. A questionnaire was sent to all those who agreed and had used Temozolomide in at least one patient with pituitary tumor. Database was closed in December 2013. A literature review was also performed. Thirty-one patients were included into the analysis. Mean age at start of Temozolomide treatment was 58.3 ± 1.9 years (± standard error). Six of the 31 (19.4%) Italian patients had a pituitary carcinoma. Twenty-five patients (80.6%) had disease control during Temozolomide treatment, while 6 patients (19.4%) had disease progression. Median follow-up after beginning Temozolomide was 43 months. Thirteen patients had tumor growth after stopping Temozolomide. The 2-year progression-free survival was 47.7% (95% CI 29.5-65.9%), while the 2-year disease control duration was 59.1% (95% CI 39.1-79.1%). Eleven patients died of progressive disease and other two patients of unrelated causes. The 2-year and 4-year overall survival rates were 83.9% (95% CI 70.7-97.1%) and 59.6% (95% CI 40.0-79.2%), respectively. Temozolomide is an additional effective therapeutic option for the treatment of aggressive pituitary tumors. The drug is well tolerated and causes few severe adverse effects. Recurrence of the tumor can occur after an initial positive response and usually portends a grim outcome.

Objectives: The purpose of this study was to examine developmental enamel defects and dental caries in very low birth weight adolescents with high risk (HR-VLBW) and low risk (LR-VLBW) compared to full-term (term) adolescents. Methods: The sample consisted of 224 subjects (80 HR-VLBW, 59 LR-VLBW, 85 term adolescents) recruited from an ongoing longitudinal study. Sociodemographic and medical information was available from birth. Dental examination of the adolescent at the 14-year visit included: enamel defects (opacity and hypoplasia); decayed, missing, filled teeth of incisors and molars (DMFT-IM) and of overall permanent teeth (DMFT); Simplified Oral Hygiene Index for debris/calculus on teeth, and sealant presence. A caregiver questionnaire completed simultaneously assessed dental behavior, access, insurance status and prevention factors. Hierarchical analysis utilized the zero-inflated negative binomial model and zero-inflated Poisson model. Results: The zero-inflated negative binomial model controlling for sociodemographic variables indicated that the LR-VLBW group had an estimated 75% increase (p < 0.05) in number of demarcated opacities in the incisors and first molar teeth compared to the term group. Hierarchical modeling indicated that demarcated opacities were a significant predictor of DMFT-IM after control for relevant covariates. The term adolescents had significantly increased DMFT-IM and DMFT scores compared to the LR-VLBW adolescents. Conclusion: LR-VLBW was a significant risk factor for increased enamel defects in the permanent incisors and first molars. Term children had increased caries compared to the LR-VLBW group. The effect of birth group and enamel defects on caries has to be investigated longitudinally from birth.

Bloodstream infection (BSI) due to Proteus mirabilis strains is a relatively uncommon clinical entity, and its significance has received little attention. This study was initiated to evaluate risk factors and treatment outcome of BSI episodes due to P. mirabilis producing extended-spectrum ␤-lactamases (ESBLs). Twenty-five BSI episodes caused by P. mirabilis occurred at our hospital (Ospedale di Circolo e Fondazione Macchi, Varese, Italy) over a 7.5-year period. Phenotypic and molecular methods were used to assess ESBL production. Clinical records of BSI patients were examined retrospectively. Demographic data, underlying diseases (according to McCabe and Jackson classification and Charlson weighted index), risk factors, and treatment outcome were investigated by comparing cases due to ESBL-positive strains to cases due to ESBL-negative strains. Eleven isolates were found to express ESBLs (TEM-52 or TEM-92). The remaining 14 isolates were ESBL negative and were uniformly susceptible to extended-spectrum cephalosporins and monobactams. Comparison of the two groups showed that previous hospitalization in a nursing home (P ‫؍‬ 0.04) and use of bladder catheter (P ‫؍‬ 0.01) were significant risk factors for infections due to ESBL-positive strains. In addition, cases due to ESBL-positive strains showed a significantly higher mortality attributable to BSI (P ‫؍‬ 0.04). BSI cases due to ESBL-negative isolates uniformly responded to therapy, whereas 5/11 cases due to ESBL-positive isolates failed to respond (P < 0.01). Use of carbapenems was associated with complete response independently of ESBL production. Therapeutic failure and mortality may occur in BSI episodes caused by ESBL-positive P. mirabilis isolates. Thus, recognition of ESBL-positive strains appears to be critical for the clinical management of patients with systemic P. mirabilis infections.Proteus mirabilis is one of the most common gram-negative pathogens encountered in clinical specimens and can cause a variety of community-or hospital-acquired illnesses, including urinary tract, wound, and bloodstream infections (BSI) (26). This organism is intrinsically resistant to nitrofurantoin and tetracycline, but it is naturally susceptible to ␤-lactams, aminoglycosides, fluoroquinolones, and trimethoprim-sulfamethoxazole (26). However, drug resistance has been increasingly reported for this species, and the diffusion of resistance to extended-spectrum cephalosporins due to the production of extended-spectrum ␤-lactamases (ESBLs) has become of great concern (37). Over the last few years, ESBL-positive P. mirabilis (ESBL-P-PM) isolates have been recovered worldwide, with a relatively high prevalence in some settings (8,18,25,32,36,39). Genes encoding ESBLs are usually located in transferable plasmids and are generally mutants of the classical TEM-1/2 type ␤-lactamases (3, 4). Moreover, coresistance to aminoglycosides, fluoroquinolones, and trimethoprim-sulfamethoxazole has been frequently reported among ESBL-P-PM strains (7,20,39). Thus, treatment of severe infec...