Management of maxillary artery pseudoaneurysm in Emergency Department: a narrative review.

Abstract: Tooth extraction is a common procedure that is performed routinely and is associated with very few risks. The formation of a pseudoaneurysm as a direct result of tooth extraction has not been widely reported in published studies; it is more frequent as a complication of orthognathic surgery (1). The purpose of this paper is to describe the literature of maxillary artery pseudoaneurysm and its diagnosis and treatment in the Emer-gency Department. The search engine we used is Pubmed. 39 studies were analyzed; mainly, they were case reports. In this study, we will analyze the cases of pseudoaneurysm formation following dental extraction and orthognotia surgery which are reported in literature.

Imaging the dome of Santa Maria del Fiore using cosmic rays.

The dome of Santa Maria del Fiore, Florence Cathedral, was built between 1420 and 1436 by architect Filippo Brunelleschi and it is now cracking under its own weight. Engineering efforts are under way to model the dome's structure and reinforce it against further deterioration. According to some scholars, Brunelleschi might have built reinforcement structures into the dome itself; however, the only known reinforcement is a wood chain 7.75 m above the springing of the Cupola. Multiple scattering muon radiography is a non-destructive imaging method that can be used to image the interior of the dome's wall and therefore ascertain the layout and status of any iron substructure in it. A demonstration measurement was performed at the Los Alamos National Laboratory on a mock-up wall to show the feasibility of the work proposed, and a lightweight and modular imaging system is currently under construction. We will discuss here the results of the demonstration measurement and the potential of the proposed technique, describe the imaging system under construction and outline the plans for the measurement.This article is part of the Theo Murphy meeting issue 'Cosmic-ray muography'.

Capecitabine with/without mitomycin C: results of a randomized phase II trial of second-line therapy in advanced biliary tract adenocarcinoma.

PURPOSE: Advanced biliary tract adenocarcinoma (BTA) is a rare tumor with a poor prognosis. Since no standard salvage chemotherapy regimen exists, we explored the activity of capecitabine alone or combined with mitomycin C. METHODS: Patients aged 18-75 years and with KPS >50, with pathological diagnosis of BTA stratified based on site and stage of disease, were randomized to receive capecitabine 2000 mg/m(2) day 1-14 alone (ARM A) or in combination with mitomycin C 6 mg/m(2) day 1 (ARM B) as second-line therapy. Cycles were repeated in both arms every 3 weeks. Tumor assessment was performed every 2 months. The primary endpoint was the probability of being progression free at 6 months (PFS-6) from treatment start. According to the Fleming design, the study aimed to enroll 26 pts per arm. An exploratory endpoint was to assess thymidylate synthase (TS) and thymidine phosphorylase (TP) expression, as biomarkers predictive for clinical outcomes of capecitabine treatment. RESULTS: Between October 2011 and 2013, 57 metastatic pts were enrolled: ARM A/B 28/29. Accordingly, 55 (26/29) pts were assessable for the primary endpoint: 2 (8%) ARM A and 3 (10%) ARM B pts were PFS-6. Main G3-4 toxicities were: hand-foot syndrome and transaminitis in 4/0%, and thrombocytopenia, diarrhea and fatigue in 0/3% of pts. No statistically significant correlation was found between TS or TP expression and pts' outcome. CONCLUSIONS: Since capecitabine yielded a disappointing outcome and the addition of mitomycin C did not improve the results, new therapeutic strategies need to be explored to improve survival in this disease setting.

Activity and safety of bevacizumab plus fotemustine for recurrent malignant gliomas.

BACKGROUND: No established chemotherapeutic regimen exists for the treatment of recurrent malignant gliomas (rMGs). Herein, we report the activity and safety results of the bevacizumab (B) plus fotemustine (FTM) combination for the treatment of rMGs. PATIENTS AND METHODS: An induction phase consisted of B 10 mg/kg days 1, 15 plus FTM 65 mg/m(2) days 1, 8, and 15. Nonprogressive patients entered the maintenance phase with B 10 mg/kg plus FTM 75 mg/m(2) every 3 weeks. The primary endpoint was response rate; secondary endpoints included safety, progression free survival (PFS), and overall survival (OS). RESULTS: Twenty-six patients affected by recurrent MGs (50% glioblastoma) were enrolled. Eight partial responses (31%) were observed. Median PFS and OS were 4 (95% C.I.: 2.8-5.1) and 6 months (95% C.I.: 4.2-7.8), respectively. Responses were significantly associated with both improved PFS and OS (P = 0.002 and P = 0.001, resp.). Treatment adverse events were mostly mild to moderate in intensity. Bevacizumab-related adverse events included grade 3 venous thromboembolic event (8%), grade 2 epistaxis (4%), hypertension (8%), and gastrointestinal perforation (4%). CONCLUSIONS: Bevacizumab plus FTM showed activity and good tolerability in pretreated MGs. Further investigations are needed in order to verify the benefits deriving from the addition of B to a cytotoxic in this clinical setting of patients.

Multivariate prognostic factors analysis for second-line chemotherapy in advanced biliary tract cancer.

BACKGROUND: The role of second-line chemotherapy (CT) is not established in advanced biliary tract cancer (aBTC). We investigated the outcome of aBTC patients treated with second-line CT and devised a prognostic model. METHODS: Baseline clinical and laboratory data of 300 consecutive aBTC patients were collected and association with overall survival (OS) was investigated by multivariable Cox models. RESULTS: The following parameters resulted independently associated with longer OS: Eastern Cooperative Oncology Group performance status of 0 (P<0.001; hazard ratio (HR), 0.348; 95% confidence interval (CI) 0.215-0.562), CA19.9 lower than median (P=0.013; HR, 0.574; 95% CI 0.370-0.891), progression-free survival after first-line CT ≥ 6 months (P=0.027; HR, 0.633; 95% CI 0.422-0.949) and previous surgery on primary tumour (P=0.027; HR, 0.609; 95% CI 0.392-0.945). We grouped the 249 patients with complete data available into three categories according to the number of fulfilled risk factors: median OS times for good-risk (zero to one factors), intermediate-risk (two factors) and poor-risk (three to four factors) groups were 13.1, 6.6 and 3.7 months, respectively (P<0.001). CONCLUSIONS: Easily available clinical and laboratory factors predict prognosis of aBTC patients undergoing second-line CT. This model allows individual patient-risk stratification and may help in treatment decision and trial design.

Use of progestagens during early pregnancy.

The term "progestagens" covers a group of molecules including both the natural female sex hormones Progesterone and 17-hydroxy Progesterone as well as several synthetic forms, all displaying the ability to bind Progesterone receptors. Several studies have used Progesterone and related steroids in the attempt to prevent spontaneous miscarriage, and treat recurrent miscarriage. The present paper aims to provide a comprehensive review of the literature on progestagens effects during early pregnancy. We looked only at the results from randomized controlled trials. We found and analyzed 15 trials on the prevention of recurrent miscarriage and 2 trials on the treatment of miscarriage. The results demonstrated that there is no evidence to support the routine use of progestagens for the treatment of threatened miscarriage.

Outcome of advanced NSCLC patients harboring sensitizing EGFR mutations randomized to EGFR tyrosine kinase inhibitors or chemotherapy as first-line treatment: a meta-analysis.

BACKGROUND: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) are effective as first-line treatment of advanced non-small-cell lung cancer patients with EGFR mutations (EGFR-M+). PATIENTS AND METHODS: We conducted a literature-based meta-analysis to quantify the magnitude of benefit with upfront EGFR TKI in EGFR-M+ patients. Meta-regression and sensitivity analyses were also carried out to identify additional predictors of outcome and to assess the influence of trial design. RESULTS: Five trials (805 patients) were identified (three trials prospectively enrolling EGFR-M+ patients and two retrospective analyses of EGFR-M+ patients). TKI significantly increased progression-free survival (PFS) [hazard ratio (HR) 0.45, 95% confidence interval (CI) 0.36-0.58, P < 0.0001] and overall response rate (ORR) (HR 2.08, 95% CI 1.75-2.46, P < 0.0001)] over chemotherapy, while significantly decreasing neutropenia. No significant difference was observed in overall survival. The rate of exon-19 mutations, female gender, and nonsmoking status were identified as additional predictors of outcome at meta-regression analysis. A significant interaction with trial design was found for both PFS (P = 0.028) and ORR (P = 0.008), suggesting a larger advantage for patients treated within prospective trials. CONCLUSIONS: In EGFR-M+ patients, first-line TKI increase both PFS and ORR by ~25%, while significantly decreasing toxicity. The role of additional predictive factors and the influence of trial design on the magnitude of the observed benefit warrant further investigation.

Pharmacological use of progesterone and 17-alpha-hydroxyprogesterone caproate in the prevention of preterm delivery.

Preterm delivery (PTD) is defined by the World Health Organization as birth before 37 completed weeks of gestation. In Western countries, PTD accounts for over 75% of all perinatal morbidity and mortality. The social importance of PTD derives from the consideration that it causes near three quarter of neonatal deaths not caused by malformations. Progesterone is a steroid hormone which plays a crucial role in each step of human pregnancy. Early in pregnancy progesterone is produced by the corpus luteum and it is fundamental for pregnancy maintenance until placenta takes over this function at 7-9 weeks of gestation. Late in pregnancy, the role of progesterone is less clear: certainly, it may be importance in maintaining uterine quiescence in the latter half of pregnancy by limiting the production of stimulatory prostaglandins and inhibiting the expression of contraction-associated protein genes (ion channels, oxytocin and prostaglandin receptors, and gap junctions) within the myometrium. In this review, the authors included those controlled clinical studies that have used either 17 hydroxy progesterone caproate (17P), or progesterone (P) or its synthetic derivatives (progestins) in order to avoid or reduce the incidence of preterm delivery, in populations of women at increased risk of preterm birth. The authors conclude that: 1) the treatment with 17P reduces the incidence of PTD in pluriparous women with a previous history of PTD or with recurrent abortion, as well as in nulliparous women with an actual risk; 2) the treatment with P reduces PTD in nulliparous women, namely in the presence of a silent cervical shortening; 3) 17P has no efficacy in multiple pregnancy and it is proven not to have adverse effects on the infants.

Metabolic syndrome and ambulatory arterial stiffness index in non-diabetic patients with primary hypertension.

Increased arterial stiffness and the presence of metabolic syndrome (MS) have been shown to predict cardiovascular events in patients with primary hypertension. We investigated the relationship between a recently proposed index of arterial stiffness derived from ambulatory blood pressure (BP) monitoring and MS in 156 untreated, non-diabetic patients with primary hypertension. Ambulatory arterial stiffness index (AASI) was defined as 1 minus the regression slope of diastolic over systolic BP readings obtained from 24-h recordings. A modified National Cholesterol Education Program definition for MS was used, with body mass index replacing waist circumference. The prevalence of MS was 23%. Patients with MS were more frequently male (0.0291) and had increased serum uric acid (P=0.0005), high-sensitivity C-reactive protein (P=0.0259), as well as total and low-density lipoprotein (LDL)-cholesterol (P=0.0374 and P=0.0350, respectively) as compared to those without MS. After adjusting for these confounders, the association between AASI and the presence of MS was statistically significant (P=0.0257). Moreover, the prevalence of increased AASI (upper tertile, that is >or=0.550) was greater in patients with MS (P=0.0156). After adjusting for age and 24-h mean BP, the presence of MS entailed a more than twofold greater risk for increased AASI (0.0280). MS is associated with increased AASI in non-diabetic patients with primary hypertension. These data support the role of this new index of arterial stiffness as a marker of risk and help to explain the high cardiovascular morbidity and mortality that is observed in hypertensive patients with MS.

Metabolic syndrome is associated with early signs of organ damage in nondiabetic, hypertensive patients.

OBJECTIVES: Hypertensive patients with metabolic syndrome (MS) are at greater risk for cardiovascular disease. To get a better understanding of the pathophysiology underlying this association, we evaluated the relationship between MS and subclinical organ damage in essential hypertensive patients. DESIGN AND SETTING: A total of 354 untreated, nondiabetic patients with primary hypertension were included in the study. A modified ATP III definition for MS was used, with body mass index replacing waist circumference. Albuminuria was measured as albumin to creatinine ratio, left ventricular mass index (LVMI) was assessed by echocardiography and carotid abnormalities by ultrasonography. RESULTS: The prevalence of MS was 25%. Patients with MS were more likely to be smokers (P = 0.004) and had higher serum uric acid levels (P = 0.004). Moreover, they showed higher urinary albumin excretion (P = 0.0004) and LVMI (P = 0.0006), increased intima-media thickness (P = 0.045), as well as higher prevalence of microalbuminuria (P = 0.03) and left ventricular hypertrophy (LVH; P = 0.003). After adjusting for age, gender and duration of hypertension, we found that the presence of MS entails a twofold greater risk for microalbuminuria (P = 0.04), LVH (P = 0.003) and carotid abnormalities (P < 0.05). When patients were stratified according to the number of components of MS, albuminuria (P = 0.002) and LVMI (P = 0.005) increased progressively across categories. CONCLUSIONS: Metabolic syndrome is associated with subclinical organ damage in nondiabetic, essential hypertensive patients. These data may, in part, explain the high cardiovascular morbidity and mortality that is observed in hypertensive patients with MS.

Creatinine clearance and signs of end-organ damage in primary hypertension.

A reduction in renal function is associated with high cardiovascular morbidity and mortality in hypertension. The aim of the present study was to investigate the relationship between creatinine clearance and subclinical organ damage in 957 never previously treated, middle-aged patients with primary hypertension. Renal function was estimated by means of the serum creatinine level using the Cockcroft-Gault formula; left ventricular hypertrophy (LVH) was determined according to electrocardiographic criteria; and retinal vascular changes were evaluated by direct ophthalmoscopy. Creatinine clearance was, on the average, 83+/-21.2 ml/min, and the prevalence of LVH and retinopathy was 13 and 49%, respectively. Creatinine clearance was inversely related to the duration of disease (r=-0.132, P<0.0001), systolic blood pressure (r=-0.110, P=0.001), serum glucose (r=-0.090, P=0.007), total cholesterol (r=-0.196, P<0.0001), and LDL-cholesterol (r=-0.196, P<0.0001). Patients in the lower quintile of creatinine clearance showed a higher prevalence of electrocardiogram (ECG) determined LVH (P=0.04), as well as retinal changes (P=0.02). The risk of having LVH or retinal vascular changes increases significantly with each s.d. decrease in creatinine clearance, regardless of traditional cardiovascular risk factors. Moreover, patients with ECG-determined LVH and retinal changes showed lower creatinine clearance as compared to those with lesser degrees of target organ involvement (P<0.01). In conclusion, a mild reduction in creatinine clearance is associated with preclinical end-organ damage in patients with normal creatinine and primary hypertension. These data may help explain the high cardiovascular mortality observed in patients with renal dysfunction. Routine evaluation of creatinine clearance could be useful for identifying patients at higher cardiovascular risk.

Pulsatile growth hormone release in normal women during the menstrual cycle.

OBJECTIVE: We sought to characterize pulsatile growth hormone (GH) release in normal women during the menstrual cycle and to document possible relationships between such characteristics and concentrations of 17 beta-oestradiol and progesterone. SUBJECTS: Fifteen women with ostensibly normal menstrual function were studied during the early follicular phase, 15 during the late follicular phase and 15 during the mid-luteal phase of the menstrual cycle. DESIGN: The phase of the menstrual cycle having been documented, blood samples were obtained from each woman every 10 minutes for 24 hours. MEASUREMENTS: Serum GH was measured in each sample by immunoradiometric assay. Pulsatile GH release was appraised utilizing the objective, statistically-based pulse detection algorithm Cluster. RESULTS: The mean (+/- SEM) integrated serum GH concentration (mU/l min) in late follicular phase women (5335 +/- 848) was higher than that observed in early follicular phase women (3156 +/- 322; P = 0.032). The integrated GH concentration calculated for mid-luteal phase women (3853 +/- 788) was intermediate between but not statistically different from that observed in early follicular (P = 0.48) and late follicular (P = 0.14) phase women. No differences in GH pulse frequency (pulses/24 hours) were found among early follicular (8.27 +/- 0.55), late follicular (7.93 +/- 0.91) or mid-luteal (8.47 +/- 0.66) phase women. Mean maximal GH pulse amplitude (mU/l) was higher in late follicular phase (8.93 +/- 1.00) than early follicular phase (5.74 +/- 0.67; P = 0.008) and mid-luteal phase (5.76 +/- 0.74; P = 0.008) women. Similarly, incremental GH pulse amplitude (mU/l) was higher in late follicular phase (7.33 +/- 0.83) than early follicular phase (4.68 +/- 0.58; P = 0.005) and mid-luteal phase (4.36 +/- 0.39; P = 0.002) women. No differences in mean pulse widths or in the interpeak valley mean GH concentrations were found among the groups. Multiple regression of each pulse parameter against serum concentrations of testosterone, 17 beta-oestradiol and progesterone revealed a significant (P = 0.045) positive correlation between maximum GH pulse amplitude and oestradiol and a significant (P = 0.04) negative correlation between maximal GH pulse amplitude and progesterone (r = 0.41). CONCLUSION: These results suggest that late follicular phase concentrations of oestradiol may enhance circulating GH via an amplitude-modulated rather than a frequency-modulated effect on the endogenous GH pulse. Progesterone may blunt this oestrogen-associated effect, thus resulting in the observed mid-luteal phase concentrations of GH. Whether these gonadal hormones act primarily at the hypothalamus and/or anterior pituitary gland remains to be clarified, but the present observations indicate that pulsatile GH release throughout the normal menstrual cycle is significantly amplitude regulated.

The benefits of a physically active workforce: an organizational perspective.

This chapter examines the role of exercise in increasing human and organizational effectiveness. First, the integration of health promotion and physical fitness interventions into human resource strategies is reviewed. This is followed by a review of the significance of exercise within general health promotion, of the impact of exercise on individual health parameters, of the carryover of individual health benefits to the organization, and, finally, by a commentary on current trends.

Attenuated pulsatile release of prolactin in men with insulin-dependent diabetes mellitus.

Pulsatile and circadian patterns of PRL release were studied in 11 insulin-dependent diabetic men by sampling blood every 10 min for 24 h and comparing the results to those obtained in 12 normal nondiabetic men. The diabetic men had a mean (+/- SE) 24-h serum PRL concentration of 5.5 +/- 0.42 micrograms/L, which was significantly lower than that in the nondiabetic men (9.3 +/- 0.86; P = 0.0008). Quantitative Cluster analysis of pulsatile PRL time series revealed a normal pulse frequency, but decreased maximal peak amplitude (6.6 +/- 0.5 vs. 11.8 +/- 1.1 micrograms/L; P = 0.0009), peak increment (2.6 +/- 0.24 vs. 4.0 +/- 0.3 micrograms/L; P = 0.009), peak area (126 +/- 15 vs. 192 +/- 19 micrograms/L.min; P = 0.03), and interpulse valley mean concentration (4.8 +/- 0.4 vs. 8.6 +/- 1.2 micrograms/L; P = 0.0007). PRL pulse incremental amplitude correlated significantly (r2 = 0.577; P = 0.007) and negatively with duration of disease. Fourier analysis disclosed a normal circadian rhythm of PRL release in diabetic men, with a mean circadian amplitude of 1.5 micrograms/L +/- 0.31, which peaked at 0201 h +/- 89 min (+/- SE). In summary, we have demonstrated significantly reduced mean 24-h serum PRL concentrations in men with poorly controlled insulin-dependent diabetes mellitus. The concomitant suppression of spontaneous PRL pulse amplitude, peak increment, and interpulse valley mean concentrations in the presence of normal pulse frequency is consistent with a reduced mass of PRL secreted per burst and/or accelerated metabolic clearance of PRL in men with type I diabetes mellitus.

Alterations in the pulsatile mode of growth hormone release in men and women with insulin-dependent diabetes mellitus.

The mechanisms responsible for the elevated levels of circulating GH observed in diabetes mellitus (DM) remain incompletely defined. To assess the episodic fluctuations in serum GH as a reflection of hypothalamic-pituitary activity, we accumulated GH concentration-time series in a total of 48 adult men and women with and without insulin-dependent DM by obtaining serum samples at 10-min intervals over 24 h. Significant pulses of GH release were subsequently identified and characterized by an objective, statistically based pulse detection algorithm (Cluster) and fixed circadian (24-h) periodicities of secretory activity, resolved using Fourier expansion time-series analysis. Compared to those in age-matched controls, integrated 24-h concentrations of GH were 2- to 3.5-fold higher in diabetic men (P = 0.002) and women (P = 0.0005). Both men and women with DM had over 50% more GH pulses per 24 h than their non-DM counterparts. In addition, maximal GH pulse amplitude was markedly elevated in the men and women with DM (P = 0.0019 and 0.0189, respectively). That the increase in maximal pulse amplitude was accounted for by greater baseline levels was documented by a higher interpulse valley mean GH concentration in the diabetics compared to the controls (P = 0.0437 and 0.0056, men and women, respectively) and the absence of any difference in incremental pulse amplitude for either sex (P greater than 0.05). DM men had larger GH pulse areas (P = 0.039) than control men, apparently accounted for by greater pulse width (P = 0.0037). Pulse areas in DM and non-DM women were indistinguishable. Time-series analysis revealed that the 24-h (circadian) rhythms of serum GH concentrations exhibited significantly increased amplitudes in the diabetic group as a whole (compared to the controls, P = 0.011). However, the times of maximal GH concentrations (acrophases) were not significantly different. As a group, serum insulin-like growth factor-I was lower in DM vs. non-DM individuals (P = 0.0014), although when separated by sex this difference did not reach statistical significance in women (P = 0.317). The present data confirm the higher circulating levels of GH previously reported to occur in individuals with poorly controlled DM. The altered frequency of GH pulses together with enhanced interpulse GH concentrations and an amplified circadian GH rhythm are compatible with hypothalamic dysfunction associated with dysregulation of somatostatin and/or GHRH secretion.(ABSTRACT TRUNCATED AT 400 WORDS)