Salvage radiotherapy in patients affected by oligorecurrent pelvic nodal prostate cancer.

PURPOSE: Metastasis-directed therapy (MDT) is an investigational treatment option in patients with oligorecurrent prostate cancer (PCa). The aim of this retrospective study is to report oncologic outcome and toxicity of elective nodal radiotherapy (ENRT) in PCa patients affected by pelvic nodal oligorecurrence. METHODS: 41 consecutive patients were treated with salvage radiotherapy. At biochemical recurrence after primary treatment, oligorecurrent disease was detected by positron emission tomography (PET) in 94% of the patients. Image-guided intensity modulated radiation therapy (IMRT) was delivered using tomotherapy. 83% of the patients received androgen deprivation therapy (ADT) in combination with ENRT. Survival analysis was performed with Kaplan-Meier method, log-rank test was used to analyze associations between survival end-points and clinical parameters. Multivariate analysis was performed using Cox proportional hazards regression models. Toxicity was registered according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0. RESULTS: The median at follow-up was 33.6 months. At 3 years, overall survival (OS), cancer-specific survival (CSS), and biochemical progression-free survival (b-PFS) were 89%, 92%, and 53%, respectively. At univariate analysis, all survival end-points were correlated with the number of positive pelvic lymph nodes at oligorecurrence (≤ 3 vs > 3). Biochemical-PFS was correlated with PSA (p = 0.034) and PSA doubling time (p = 0.004) at oligorecurrence. At multivariate analysis, no independent variable was statistically significant. No patient experienced grade ≥ 2 late toxicity after radiotherapy. CONCLUSIONS: The number of metastatic lymph nodes and PSA doubling time seems to be important prognostic factors in the pelvic oligorecurrent setting. Salvage radiotherapy combined with short-course ADT might be a valid treatment strategy.

Micronutrients in support to the one carbon cycle for the modulation of blood fasting homocysteine in PCOS women.

PURPOSE: Fasting blood homocysteine is increased in PCOS women and is involved in several of its co-morbidities including cardiovascular disease and infertility. Corrective interventions based on the administration of supra-physiologic doses of folic acid work to a low extent. We aimed to test an alternative approach. METHODS: This was a prospective, randomized, parallel group, open label, controlled versus no treatment clinical study. PCOS women aged > 18, free from systemic diseases and from pharmacological treatments were randomized with a 2:1 ratio for treatment with activated micronutrients in support to the carbon cycle (Impryl, Parthenogen, Switzerland-n = 22) or no treatment (n = 10) and followed-up for 3 months. Fasting blood homocysteine, AMH, testosterone, SHBGs, and the resulting FTI were tested before and at the end of the follow-up. RESULTS: The mean baseline fasting blood homocysteine was above the normal limit of 12 µMol/L and inversely correlated with SHBG. AMH was also increased, whereas testosterone, SHBG, and FTI were within the normal limit. The treatment achieved a significant reduction of homocysteine, that did not change in the control group, independently of the starting value. The treatment also caused an increase of AMH and a decrease of SHBGs only in the subgroup with a normal homocysteine at baseline. CONCLUSIONS: In PCOS ladies, blood homocysteine is increased and inversely correlated with the SHBGs. Physiologic amounts of activated micronutrients in support to the carbon cycle achieve a reduction virtually in all exposed patients. Whether this is of clinical benefit remains to be established.

Terlipressin-induced modifications of Doppler ultrasound signals of systemic arteries in preterm infants with vasoactive-resistant patent ductus arteriosus: A pilot study.

PURPOSE: To study the effects of terlipressin (TP) infusion on systemic perfusion, estimated with pulsed-wave Doppler ultrasonography of systemic arteries, in a population of extremely low birth-weight (ELBW) preterm infants with vasoactive-resistant ductus arteriosus. METHODS: This prospective, observational cohort included, during five years, 12 ELBW infants with hemodynamically significant patent ductus arteriosus and absent or reversed diastolic flow at Doppler ultrasonography of systemic arteries, despite treatment and high-dose vasoactive support. We measured flow velocity of the anterior cerebral, right renal, and superior mesenteric arteries before and after TP infusion. Changes were evaluated by Spearman's rho coefficient analysis, Wilcoxon signed-rank, and Friedman test. RESULTS: Time-averaged mean velocity of the renal artery (P = .028) increased, while renal pulsatility (P = .010) and resistance (P = .004) indexes, and cerebral artery resistance index (P = .021) decreased after TP infusion. Time-averaged mean velocity of the anterior cerebral artery proportionately increased with dopamine dose (rho = 0.678; P = .015), but showed opposite shifts after TP (rho = -0.662; P = .024). CONCLUSIONS: These changes suggest that TP may improve systemic perfusion in the ELBW infants with vasoactive-resistant ductus arteriosus.

Dermatitis caused by arthropods in domestic environment: an Italian multicentre study.

BACKGROUND: Skin diseases caused by mites and insects living in domestic environments have been rarely systematically studied. OBJECTIVES: To study patients with dermatitis induced by arthropods in domestic environment describing their clinical features, isolating culprit arthropods and relating the clinical features to the parasitological data. METHODS: The study was performed in 105 subjects with clinical and anamnestic data compatible with the differential diagnosis of ectoparasitoses in domestic environments. Clinical data and arthropods findings obtained by indoor dust direct examination were studied. RESULTS: Indoor dust direct examination demonstrated possible arthropods infestation in 98 subjects (93.3%), more frequently mites (56.1%) (mainly Pyemotes ventricosus and Glycyphagus domesticus) than insects (43.9%) (mainly Formicidae and Bethylidae). Strophulus (46.9%) and urticaria-like eruption (36.7%) in upper limbs and trunk with severe extent were prevalent. Itch was mostly severe (66.3%) and continuous (55.1%). Ectoparasitoses occurred frequently with acute course in summer (44.9%) and spring (30.6%). CONCLUSIONS: Possible correlation between clinical and aetiological diagnosis of arthropods ectoparasitoses in domestic environments needs the close cooperation between dermatologist and parasitologist. This is crucial to successfully and definitely resolve skin lesions by eradicating the factors favouring infestation.

Cardiovascular disease risk burden in primary Sjögren's syndrome: results of a population-based multicentre cohort study.

OBJECTIVE: Systemic autoimmune diseases, in particular systemic lupus erythematosus and rheumatoid arthritis, are characterized by a high risk of premature cardiovascular (CV) events. Disease-related characteristics and traditional CV disease risk factors may contribute to atherosclerotic damage. However, there are limited data on the risk of overt CV events in primary Sjögren's syndrome (pSS). METHODS: We retrospectively analysed a cohort of patients with 1343 pSS. Disease-related clinical and laboratory data, traditional CV disease risk factors and overt CV events were recorded. Prevalence of traditional CV disease risk factors and of major CV events was compared between a subgroup of 788 female patients with pSS aged from 35 to 74 years and 4774 age-matched healthy women. RESULTS: Hypertension and hypercholesterolaemia were more prevalent, whereas smoking, obesity and diabetes mellitus were less prevalent, in women with pSS than in control subjects. Cerebrovascular events (2.5% vs. 1.4%, P = 0.005) and myocardial infarction (MI) (1.0% vs. 0.4%, P = 0.002) were more common in patients with pSS. In the whole population, central nervous system involvement (odds ratio (OR) 5.6, 95% confidence interval (CI) 1.35-23.7, P = 0.02) and use of immunosuppressive therapy (OR 1.9, 95% CI 1.04-3.70, P = 0.04) were associated with a higher risk of CV events. Patients with leucopenia had a higher risk of angina (P = 0.01). CONCLUSIONS: pSS is associated with an increased risk of cerebrovascular events and MI. Disease-related clinical and immunological markers may have a role in promoting CV events.

Maternal smoking does not affect the amount of cell-free fetal DNA in maternal plasma during the 1st trimester of pregnancy.

CffDNA, from 344 non-smoking, 38 smoking and 33 ex-smoking pregnant women at 11 (+0)-13 (+6) gestational weeks, was extracted and quantified by the multicopy DYS14, as the fetal DNA marker and using the quantitative real-time PCR 7300 detection system. The smoking habit was based on maternal self-report, confirmed by cotinine levels and male fetuses were verified by phenotype at birth. The genders of newborns were compared with DYS14-cffDNA analysis, achieving a 100% diagnostic accuracy of the test. A total of 177 non-smokers, 18 smokers and 22 ex-smoker pregnancies with male fetuses were identified by the cffDNA concentration. Results showed that smoking status was not associated with different amounts of DYS14-cffDNA (p = 0.159), suggesting the possibility of offering cffDNA testing to all pregnant women, even if they are active smokers or ex-smokers, and the test can be unadjusted for smoking status.

Renal echo-3D and microalbuminuria in children of diabetic mothers: a preliminary study.

Maternal diabetes has assumed epidemic relevance in recent years and animal studies have provided some evidence that it may cause abnormalities in renal development and a reduction in nephron endowment in the offspring; however, human data are lacking. The renal cortex contains ∼95% of the glomeruli and its volume could be taken as a surrogate measure of glomerular number; based on this assumption, we measured renal cortex volume and in addition, microalbuminuria in a homogeneous sample of 42 children of diabetic (pregestational, n = 13, and gestational, n = 29) mothers, compared with 21 healthy children born of non-diabetic mothers. The offspring of diabetic mothers showed a significant reduction of renal cortex volume and higher albumin excretion compared with controls, possibly attributable to a reduction in the number of nephrons and the difference was statistically significant (P < 0.001). Although further studies on a larger sample are necessary, our preliminary findings suggest that maternal diabetes may affect renal development with sequelae later in life, requiring closer monitoring and follow-up. Furthermore, the importance of strict maternal diabetes management and control must be emphasized.

Expander/implant breast reconstruction before radiotherapy: outcomes in a single-institute cohort.

BACKGROUND AND PURPOSE: Radiotherapy (RT) of reconstructed breasts was associated with major complications and poor cosmetic outcome. The present study assessed complication rates, the link between risk factors and prosthesis removal, as well as cosmetic outcomes. PATIENTS AND METHODS: From 1997 to 2009, 101 consecutive patients received RT after breast reconstruction because of risk factors for relapse (92) or because relapse had occurred (9). At RT, 90 patients had temporary tissue expanders and 11 had permanent implants. Twelve patients underwent neo-adjuvant chemotherapy; all patients received adjuvant chemo- and/or hormone therapy. RESULTS: At a median follow-up of 50 months, late toxicities occurred in 28 patients: pain in 7, lymphedema in 6, G1 cutaneous toxicity in 5, and subcutaneous toxicity in 19 (2G1, 9G2, 7G3, 1G4), with more than one side effect in 12. In 8 patients the prosthesis ruptured (3), was displaced (3), was displaced and ruptured (1), or lost shape (1). Capsular contracture was classified in 89 patients as IA in 14, IB in 47, II in 10, III in 11, and IV in 7. Twelve prostheses (11.9%) were removed. The only significant factor for prosthesis removal was age (p = 0.007). Judgments of cosmetic results were available from 81 physicians and 84 patients. Outcome was excellent/good in 58/81 physician judgments and in 57/84 patient evaluations. Overall inter-rater agreement on outcome was good (κ-value 0.64; 95% CI: 0.48-0.79). CONCLUSION: RT to reconstructed breasts was associated with low rates of late toxicity and prosthesis removal. Cosmetic outcomes were, on the whole, good to excellent.

Adolescent exposure to nicotine and/or the cannabinoid agonist CP 55,940 induces gender-dependent long-lasting memory impairments and changes in brain nicotinic and CB(1) cannabinoid receptors.

We have analysed the long-term effects of adolescent (postnatal day 28-43) exposure of male and female rats to nicotine (NIC, 1.4 mg/kg/day) and/or the cannabinoid agonist CP 55,940 (CP, 0.4 mg/kg/day) on the following parameters measured in the adulthood: (1) the memory ability evaluated in the object location task (OL) and in the novel object test (NOT); (2) the anxiety-like behaviour in the elevated plus maze; and (3) nicotinic and CB(1) cannabinoid receptors in cingulated cortex and hippocampus. In the OL, all pharmacological treatments induced significant decreases in the DI of females, whereas no significant effects were found among males. In the NOT, NIC-treated females showed a significantly reduced DI, whereas the effect of the cannabinoid agonist (a decrease in the DI) was only significant in males. The anxiety-related behaviour was not changed by any drug. Both, nicotine and cannabinoid treatments induced a long-lasting increase in CB(1) receptor activity (CP-stimulated GTPγS binding) in male rats, and the nicotine treatment also induced a decrease in nicotinic receptor density in the prefrontal cortex of females. The results show gender-dependent harmful effects of both drugs and long-lasting changes in CB(1) and nicotinic receptors.

Postpartum hysterectomy: a regional multicentre analysis in Italy.

To estimate prevalence, indications, risk factors and complications associated with emergency postpartum hysterectomy and to compare different results in Teaching and District Hospitals we designed a retrospective analysis in 34 cases of postpartum hysterectomy performed from 1 January 2002 to 31 December 2006, in three different obstetrics and gynaecology units (one University Hospital and two Regional Hospitals). The prevalence of postpartum hysterectomies was 2.2 per 1,000 deliveries. District Hospitals revealed a significantly increased risk (OR: 2.28). Severe complications were few. No deaths were reported. Considering the totality of patients and cases of District Hospitals, placenta praevia was the main cause of hysterectomy (44.1% and 52.2%, respectively), but uterine atony had a major prevalence in the Teaching Hospital (45.4%). Operating time was significantly longer (p = 0.0001) and the blood loss was significantly more important (p = 0.041) in the Teaching Hospitals.

[The prevalence of accidental poisoning in a hospital pediatric unit of Latium]. / Prevalenza delle intossicazioni accidentali in una divisione ospedaliera pediatrica del Lazio.

The aim of this study was to investigate the trend of accidental poisoning among children, over a period of fifteen years, from 1990 to 2004, in the pediatric wards of a hospital in Latium (Italy). The prevalence of childhood poisoning was calculated based on the medical records of the pediatric unit of the hospital. The derived data was divided into different categories according to age, gender and types of poisoning. The results of this study show a decrease in accidental pediatric poisoning; according to the literature the frequency of poisoning was higher in males, under the age of 2 years, than females. Trends show an increase in pharmaceutical poisonings. The present study underlines the need for continuous information on prevention and educational programs organized by the Institutions, territorial sanitary services and GP with the aim of increasing the awareness of parents regarding the risk factors of poisoning.

Circulating adipocytokines in non-diabetic and Type 1 diabetic children: relationship to insulin therapy, glycaemic control and pubertal development.

AIM: To determine the influence of Type 1 diabetes mellitus on circulating adipocytokines in children. METHODS: The circulating concentrations of leptin, adiponectin, resistin and tumour necrosis factor (TNF)-alpha were measured in 91 children, aged 11.1 +/- 2.7 years, with Type 1 diabetes mellitus (T1DM). Ninety-one healthy children were selected as control subjects. RESULTS: Body mass index-adjusted leptin concentrations were higher in the pubertal diabetic children compared with the control children. There was a significant positive correlation between leptin and daily insulin dose in the diabetic group. Circulating adiponectin concentrations were higher in the prepubertal diabetic children and were positively associated with HbA(1c). Resistin concentrations were lower in the prepubertal non-diabetic subjects compared with the pubertal non-diabetic children, whose values were higher than those of the diabetic children. TNF-alpha concentrations were similar in non-diabetic and diabetic children. CONCLUSIONS: Circulating concentrations of adipocytokines are abnormal in Type 1 diabetic children, although the direction of change differs by cytokine. Pubertal development, in addition to insulin treatment and glycaemic control, also influences the concentrations.

Recovery of sexual function after nerve-sparing radical retropubic prostatectomy: is cavernous nitric oxide level a prognostic index?

The preservation of NANC nerve fibers (producing nitric oxide, NO) is necessary for erection recovery after retropubic radical prostatectomy (RRP). Yet, it is impossible to establish when and if a patient will recover erections; therefore, we investigate the prognostic value of cavernous blood NO levels on this parameter. Nerve-sparing RRP was performed on 14 patients for localized prostate cancer. We evaluated all patients 3 months after surgery by IIEF score: no patients had erections. A cavernous blood sample was also taken to determine NO levels (as nitrite). Patients were evaluated again 18 months after surgery. In six cases, erectile function was compromised, whereas in seven cases, potency was restored. Statistical analysis showed a relationship between nitrite levels in cavernous blood 3 months after surgery and the recovery or erectile function at 18 months. We propose that cavernous NO blood levels are a prognostic index of erection recovery.

Impaired decision-making in opiate-dependent subjects: effect of pharmacological therapies.

Cognitive dysfunction is a major feature of drug addiction. In the present paper, we compared the decision-making ability using the Iowa gambling task of methadone- and buprenorphine-maintained individuals to non opiate-dependent drug-free controls. Buprenorphine-maintained individuals performed better than methadone-maintained individuals, and not differently than non opiate-dependent controls. In addition, methadone-maintained individuals had more perseverative errors on the Wisconsin card sorting task (WCST) as compared with non opiate-dependent drug-free controls whereas buprenorphine-maintained individuals had intermediate scores. Scores on Weschler adult intelligence scale (WAIS-R) were similar for methadone- and buprenorphine-maintained individuals whereas drug-free controls had significantly higher scores. In addition, both opiate-dependent groups performed more poorly than drug-free controls on the Benton visual retention test (BVRT). The results suggest that buprenorphine in contrast to methadone improves decision-making, and thus may be more effective in rehabilitation programs of opiate-dependent subjects and this improvement may be related to its distinct pharmacological action as a k antagonist.

Circulating acylated and total ghrelin and galanin in children with insulin-treated type 1 diabetes: relationship to insulin therapy, metabolic control and pubertal development.

OBJECTIVE: To study the circulating levels of two gut-derived peptides in children with type 1 (insulin-dependent) diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: Plasma levels of ghrelin, both total ghrelin (TG) and the acylated form (AG), and galanin and their relationships with insulin dosage, metabolic control, IGFBP-1, body mass and pubertal development were evaluated in 91 children, aged 11.1 +/- 2.7 years, affected by IDDM and treated with insulin. Ninety-one healthy children were selected as controls. RESULTS: Body mass index (BMI)-adjusted levels of both forms of ghrelin were reduced in IDDM compared with healthy subjects, with greater values in prepubertal than pubertal IDDM subjects. A negative association was found between AG and fasting insulin serum levels and insulin resistance [measured by using the homeostasis model assessment of insulin resistance (HOMA IR)] among the healthy children. IDDM children showed a negative association of their plasma ghrelin (both acylated and total) with daily insulin dosage, and the three adiposity indices (BMI, skinfold thickness and percentage fat mass). IGFBP-1 levels were higher among the IDDM children without any association with ghrelin serum values. BMI-adjusted plasma levels of galanin were higher among IDDM compared to healthy subjects, irrespective of sex or pubertal development. Greater values for galanin were found among pubertal than prepubertal subjects in both groups without any significant differences between the genders. A positive association was found between galanin and BMI in both groups and between galanin and haemoglobin A1c (HbA1c) among the IDDM children. No relationship existed between either galanin and fasting serum insulin among the healthy subjects or galanin and both insulin dosage or duration of treatment among the IDDM subjects. CONCLUSIONS: The associations found between both ghrelin and galanin with adiposity indices could be considered as an indirect signal of involvement of the two peptides in the development of the nutritional status of the IDDM adolescents. The reduction in both forms of ghrelin could be involved in the development of the body mass increase of IDDM subjects with opposite effects, either influencing insulin sensitivity or exerting a compensatory restraint of feeding.

BMI-conditional standard of leptin serum values in children: proposal of a statistical procedure for the analysis of influencing variables.

In order to define serum leptin values in children, its concentration was assayed in 3,453 children, 5-14 years old, and body mass index (BMI) and pubertal development were recorded. Insulin, testosterone (in males) and 17beta-estradiol (in females), the sum of four skinfold thicknesses (SST), waist-to-hip ratio, and body fat mass were also determined in 1,601 children. Analysis of multicollinearity effects on estimated models demonstrated a quasi-linear correlation between SST and BMI, the former being prevalent. Although other variables were strongly correlated with leptin, assuming only SST as predictor, R2 yielded a value of 0.711 in males and 0.607 in females. When the other variables were added, R2 increased by about 0.03 in both sexes. BMI and SST were the most important of all the predictors and each can act as a sort of proxy for the others. When the z-scores of BMI of all 3,453 children were subdivided into deciles, any correlation with leptin was no more significant inside each BMI z-score range. This study demonstrates that subcutaneous fat mass may be considered the prevalent determinant factor. The adopted statistical procedure furnished results useful for reference values based on BMI z-score as a simple and appropriate evaluation for serum leptin concentrations in children.

Contribution of MHC class I chain-related A (MICA) gene polymorphism to genetic susceptibility for systemic lupus erythematosus.

OBJECTIVE: To evaluate the contribution of the MHC class I chain-related A (MICA) gene polymorphism to the genetic risk of systemic lupus erythematosus (SLE). METHODS: HLA-DRB1-DQA1-DQB1 genotyping, MICA exon 5 microsatellite genotyping and HLA-B8 genotyping were performed in 48 Italian SLE patients and in 158 healthy control subjects. RESULTS: Of HLA class II haplotypes, only DRB1*03-DQA1*0501-DQB1*0201 (DR3-DQ2) was significantly more frequent among SLE patients than among healthy control subjects [odds ratio (OR) = 6.5, corrected P < 0.0026]. HLA-B8 was detected in 31% SLE patients and 13% healthy control subjects (OR = 3.0, P = 0.005). The allele-wise comparison between patients and controls showed that both MICA5 (OR = 2.5, corrected P < 0.0005) and MICA5.1 (OR = 2.4, corrected P < 0.0005) were positively and MICA9 (OR = 0.2, corrected P < 0.0005) was negatively associated with the disease. The MICA5/5.1 genotype was positively associated with SLE (OR = 28.9, corrected P < 0.0015) also in subjects negative for DR3-DQ2 (OR > 22.6, corrected P < 0.011). The simultaneous presence of DR3-DQ2 and MICA5.1 was detected in 15/48 (31%) SLE and in 10/158 (6%) healthy control subjects (OR = 6.7, corrected P < 0.011). The simultaneous combination of DR3-DQ2 and MICA5 was found in 10/48 (21%) SLE patients and in only 1/158 healthy control subjects (OR = 41.3, corrected P < 0.011). Logistic regression analysis showed the independent positive associations of MICA5 and MICA5.1 and negative association of MICA9 with the disease, and revealed that the interaction of the three major markers (DR3-DQ2, MICA5 and MICA5.1) was associated with increasing genetic risk, which was highest (OR > 30.3) in DR3-DQ2-positive subjects carrying the MICA5-5.1 genotype. CONCLUSIONS: Our study provides the first demonstration of the independent association of the MICA gene polymorphism with genetic risk of SLE.