MRI-derived radiomics to guide post-operative management of glioblastoma: Implication for personalized radiation treatment volume delineation.

Background: The glioblastoma's bad prognosis is primarily due to intra-tumor heterogeneity, demonstrated from several studies that collected molecular biology, cytogenetic data and more recently radiomic features for a better prognostic stratification. The GLIFA project (GLIoblastoma Feature Analysis) is a multicentric project planned to investigate the role of radiomic analysis in GB management, to verify if radiomic features in the tissue around the resection cavity may guide the radiation target volume delineation. Materials and methods: We retrospectively analyze from three centers radiomic features extracted from 90 patients with total or near total resection, who completed the standard adjuvant treatment and for whom we had post-operative images available for features extraction. The Manual segmentation was performed on post gadolinium T1w MRI sequence by 2 radiation oncologists and reviewed by a neuroradiologist, both with at least 10 years of experience. The Regions of interest (ROI) considered for the analysis were: the surgical cavity ± post-surgical residual mass (CTV_cavity); the CTV a margin of 1.5 cm added to CTV_cavity and the volume resulting from subtracting the CTV_cavity from the CTV was defined as CTV_Ring. Radiomic analysis and modeling were conducted in RStudio. Z-score normalization was applied to each radiomic feature. A radiomic model was generated using features extracted from the Ring to perform a binary classification and predict the PFS at 6 months. A 3-fold cross-validation repeated five times was implemented for internal validation of the model. Results: Two-hundred and seventy ROIs were contoured. The proposed radiomic model was given by the best fitting logistic regression model, and included the following 3 features: F_cm_merged.contrast, F_cm_merged.info.corr.2, F_rlm_merged.rlnu. A good agreement between model predicted probabilities and observed outcome probabilities was obtained (p-value of 0.49 by Hosmer and Lemeshow statistical test). The ROC curve of the model reported an AUC of 0.78 (95% CI: 0.68-0.88). Conclusion: This is the first hypothesis-generating study which applies a radiomic analysis focusing on healthy tissue ring around the surgical cavity on post-operative MRI. This study provides a preliminary model for a decision support tool for a customization of the radiation target volume in GB patients in order to achieve a margin reduction strategy.

Co-heredity of silent CAP + 1570 T>C (HBB:c*96T>C) defect and severe ß-thal mutation: a cause of mild ß-thalassemia intermedia.

INTRODUCTION: During an intensive screening program aimed at identifying the healthy carriers of thalassemia and the couples at risk of bearing an affected fetus, a rare single nucleotide variation (SNV), CAP + 1570 T > C (HBB:c*96T > C), located 12 nucleotides upstream of the polyadenylation signal in 3'UTR of the beta globin gene was identified. It was previously reported as a ß+ thalassemia mutation and later as a plain polymorphism. METHODS: Genotype identification of globin gene mutations was carried out using sequencing analysis, GAP-PCR, and MLPA methods. RESULTS: CAP + 1570 T > C (HBB:c*96T > C) was found in 39 heterozygotes, in one case in homozygous state and in thirteen cases of co-inheritance of this nucleotide substitution with other mutations in globin genes. Carriers of this mutation showed a 'silent' phenotype without appreciable microcytosis and hypochromia, so they cannot be differentiated from noncarrier individuals. Compound heterozygotes for this mutation and severe ß-thal mutations showed a variable phenotype ranging from ß-thal carrier to mild form of ß-thalassemia intermedia, revealing new aspects and allowing to better understand the clinical implications of this nucleotide substitution that can be classified as a silent ß-thalassemic defect. CONCLUSION: Data reported in this study indicate the need of investigating partner of ß-thalassemia carrier by complete sequencing analysis of ß-globin gene and of providing an appropriate genetic counseling for couples at risk undergoing prenatal diagnosis.

Incidence of haemoglobinopathies in Sicily: the impact of screening and prenatal diagnosis.

BACKGROUND: Haemoglobinopathies are a major public health problem in Sicily: it was estimated a frequency of 1/245 couples are at risk of haemoglobinopathies. This paper reviews legislative actions, prevention activities, carrier screening, genetic counselling, foetal sampling and laboratory methodology analysis evolution reporting the results of 30 years of prevention actions to assess the efficiency of our preventative programme in the control of haemoglobinopathies in Sicily. METHODS: This programme consisted principally of five phases: legislative actions, public awareness campaign, carrier screening, genetic counselling and prenatal diagnosis. RESULTS: These programmes have been very effective, which we can see from a greater public awareness of thalassaemia and its prevention in the target population furthermore by a marked decline in the incidence of thalassaemia major and sickle cell anaemia from 1 in 245 live births in the absence of prevention to 1 in 2000, with a reduction in about 85%. The residual cases were because of a conscious choice by expecting parents in relation to improved life expectancy as well as improved quality of life of the affected patients. CONCLUSION: The study suggests that public health authorities should act and invest in a similar programme for prevention of thalassaemia, as well as in relation to the increased survival of patients and the consequent organ complications.

Genistein effects on quality of life and depression symptoms in osteopenic postmenopausal women: a 2-year randomized, double-blind, controlled study.

SUMMARY: Postmenopausal estrogen decline is implicated in several age-related physical and psychological changes in women, including decreases in perceived quality of life. The phytoestrogen genistein at a dose of 54 mg daily in osteopenic postmenopausal women after 2 years implies an improvement on quality of life and depression symptoms. INTRODUCTION: Postmenopausal estrogen decline is implicated in several age-related physical and psychological changes in women, including decreases in perceived quality of life (QoL). A number of trials with hormone therapy showed beneficial effects of the intervention on quality of life parameters. However, because of known or suspected serious side effects of conventional hormone therapy, there is a need for alternatives. METHODS: We conducted a double-blind randomized placebo-controlled trial using the isoflavone genistein, 54 mg, or placebo for 2 years. In this trial, we recruited 262 postmenopausal women aged 49 to 67 years. RESULTS: At baseline, after 1 year, and at final visit, participants filled in the Short Form of 36 questions (SF-36) and the Zung Self-rating Depression Scale (ZSDS). For the placebo group, scores on all dimensions of the SF-36 decreased after 1 and 2 years. The genistein group showed increases on all dimensions of the SF-36 at the end of the study. There were, however, statistically significant differences in changes of scores between the two intervention groups. For the ZSDS, similarly, significant differences were found between groups. CONCLUSION: In conclusion, the findings of this randomized trial showed that genistein improves quality of life (health status, life satisfaction, and depression) in osteopenic postmenopausal women.

Correspondence between first-trimester fasting glycaemia, and oral glucose tolerance test in gestational diabetes diagnosis.

AIM: To evaluate the correspondence between first-trimester fasting glycaemia and the results of the OGTT in diagnosing gestational diabetes (GDM). METHODS: The medical records of all consecutive women who had undergone a diagnostic OGTT, performed according to the IADPSG, during the past year were retrospectively reviewed. All first-trimester fasting glucose values greater or equal to 5.1 mmol/L (92 mg/dL), recommended as a diagnostic value, were also verified for each patient in this cohort. Moreover, a ROC curve and a multiple logistic-regression model were constructed to calculate the predictive capability of this cut-off value in diagnosing GDM. RESULTS: In our population of 738 eligible pregnant women, an 11.9% prevalence of GDM was revealed by OGTT. However, when the first-trimester fasting glucose value for each patient was retrospectively considered, there were a further 29 patients who should have been diagnosed as GDM cases (glycaemia ≥ 5.1 mmol/L), although their OGTT was normal. Yet, when the value of fasting glucose was considered not diagnostic, but only predictive, an AUC of 0.614 (95% CI: 0.544-0.684) and an aOR of 7.1 (95% CI: 3.8-13.1) was obtained in these patients compared with the reference group (fasting glucose < 5.1 mmol/L). CONCLUSION: There was no complete correspondence in diagnosing GDM between the first-trimester fasting glucose value and the results of a 2-h 75-g OGTT performed early in the third trimester. However, albeit not diagnostic, a fasting glucose value greater or equal to 5.1 mmol/L may be considered a highly predictive risk factor for GDM.

Pregnancy outcome following mid-trimester amniocentesis.

To determine the institutional pregnancy complications rate associated with genetic amniocentesis and ascertain whether procedural variables or pre-existing factors may determine an increased risk of having a procedural-related fetal loss, we retrospectively evaluated all the consecutive amniocentesis, with known pregnancy outcome (n = 2990), performed between January 2001 and December 2009 by two very experienced clinicians. The patients who had counselling in the same period but declined to undergo amniocentesis represent the control group (n = 487). A total of 30 fetal losses occurred within 24 weeks' gestation (1%), while in the control group, we had four losses (0.8%). Procedural variables (transplacental sample, multiple needle insertions and gestational age) were not found to be predictive of increased fetal loss rate. Previous vaginal bleeding increased the risk of pregnancy loss after amniocentesis with an OR 4.1 (95% CI 2.0-8.7); on the contrary, a history of two or more miscarriages is not associated with a greater fetal loss rate, while the increased percentage (OR 3.4, 95% CI 1.2-9.0) in patients affected by uterine myoma appears connected, after the comparison with the control group, with the presence of fibroids rather than procedure.

Effects of prepregnancy body mass index and weight gain during pregnancy on perinatal outcome in glucose-tolerant women.

AIM: The aim of this study was to determine the effects of maternal prepregnancy body mass index (BMI) and weight gain during pregnancy on perinatal outcome in non-diabetic women. METHODS: The clinical records of consecutive women who had undergone a glucose challenge test (GCT) and then delivered in our university hospital between January 2004 and December 2009 were retrospectively reviewed. Prepregnancy BMI and pregnancy weight gain were classified according to the US Institute of Medicine guidelines (1990). RESULTS: Of the eligible 2225 patients, obese and overweight women had a greater percentage of macrosomic babies (17.7% and 8.9%, respectively) compared with normal weight women (4.5%). However, when considered according to weight gain during pregnancy, the results were statistically significant only for excess weight gain in the obese (OR: 8.3, 95% CI: 2.4-28.4) and overweight (OR: 2.9, 95% CI: 1.2-6.8) groups. Also, the surgical delivery rate was significantly higher in the obese vs normal weight women (56% vs 36%, respectively) although, in this case, there was no difference according to normal and excess weight gain during pregnancy (OR: 1.4, 95% CI: 0.7-2.6). CONCLUSION: Overweight and obese women have an increased risk rate of macrosomia that can be limited by well-controlled weight gain during pregnancy. There was also a significantly higher rate of surgical delivery in the obese compared with the normal weight group that was, however, independent of excessive weight gain during pregnancy.

Efficacy of genistein aglycone on some cardiovascular risk factors and homocysteine levels: A follow-up study.

BACKGROUND AND AIM: Recent evidence suggests that genistein aglycone may act beneficially on surrogate cardiovascular risk markers in postmenopausal women. We assessed the effects of genistein aglycone on some cardiovascular risk factors and homocysteine levels after 3-years of continued therapy in a cohort of osteopenic, postmenopausal women. METHODS AND RESULTS: The parent study was a randomized, double-blind, placebo-controlled trial involving 389 postmenopausal women with low bone mass for 24 months. Subsequently, a subcohort (138 patients) continued therapy for an additional year. Participants received 54mg of genistein aglycone (n=71) or placebo (n=67), daily. Both arms received calcium and vitamin D(3) in therapeutic doses. Moreover, 4 weeks before randomization procedures and during our follow-up study, all patients received dietary instructions in an isocaloric fat-restricted diet. Blood lipid profiles, fasting glucose and insulin, insulin resistance (HOMA-IR), fibrinogen, osteoprotegerin (OPG) and homocysteine at baseline and after 24 and 36 months of treatment were measured. Compared to placebo, genistein significantly decreased fasting glucose and insulin, HOMA-IR, fibrinogen and homocysteine after 24 and 36 months of treatment. By contrast, isoflavone administration did not affect high-density lipoprotein cholesterol and triglycerides though serum OPG was higher in the genistein recipients. There were no differences in adverse events or discomfort between groups. Results on routine biochemical, liver function, and hematologic testing did not change over time in placebo or genistein group. CONCLUSIONS: After 3-years of treatment, genistein aglycone plus calcium, vitamin D(3) and a healthy diet showed positive effects on some cardiovascular risk factors and homocysteine levels in a cohort of postmenopausal women with low bone mass.

Genistein effects on quantitative ultrasound parameters and bone mineral density in osteopenic postmenopausal women.

UNLABELLED: This study aimed at evaluating the effects of genistein (54 mg/die) on calcaneus and phalanges ultrasound (QUS) parameters and bone mineral density in osteopenic postmenopausal women. We concluded that genistein prevented bone loss in the osteopenic postmenopausal women and improves QUS parameters at the calcaneus and phalanges. INTRODUCTION: The purpose of the study was to evaluate the effects of genistein (54 mg/die) on quantitative ultrasound (QUS) parameters of the calcaneus and hand phalange and on bone mineral density (BMD) in osteopenic postmenopausal women. METHODS: One hundred thirty-eight women (age 49-67 years) were assigned to receive genistein or placebo. Bone status was assessed by measuring the anteroposterior lumbar spine and femoral neck BMD by dual energy X-ray absorptiometry and by ultrasound of the calcaneus (Achilles Plus, GE, Lunar) and of the phalanges (Bone Profiler. IGEA) at baseline and after a 1- and 2-year treatment. RESULTS: At the end of the experimental period, genistein had significantly increased BMD in the femur and lumbar spine (p < 0.001). The stiffness index, amplitude-dependent speed of sound, and bone transmission time in the genistein group had increased significantly at the end of study (+5.3, p < 0.001; +3.6%, p < 0.001; +4.6, p < 0.001, respectively). CONCLUSIONS: This study confirms that genistein prevented bone loss in the osteopenic postmenopausal women and it improves the QUS parameters.

Compliance with hormone replacement therapy in postmenopausal Sicilian women.

OBJECTIVE: To verify the compliance with hormone replacement therapy (HRT) over 2 years in a population of postmenopausal women in East Sicily. STUDY DESIGN: Patients starting hormonal therapy for the first time were enrolled in this study. A telephone survey was then conducted after 3, 6, 12 and 24 months and the reasons for any discontinuation were recorded. RESULTS: Of a total of 138 women who agreed to be enrolled in this prospective longitudinal study 72 were still taking the treatment after 1 year and only 56 at the end of the study, although only three patients reported that they had experienced no benefit. CONCLUSIONS: Type of work, surgical menopause and previous use of oral contraceptives were significantly statistically associated with better HRT compliance. Side effects and fear of breast cancer, which we maintain is exaggerated by the women and their family doctors, were the commonest reasons for early discontinuation of the hormonal treatment.

[Fournier's gangrene: remarks on two clinical cases]. / Le gangrène de Fournier: remarques sur deux cas cliniques.

Fournier's gangrene is a genital and perineal necrotizing fascitiis with a rapid evolution. It's an affection caused by aerobic and anaerobic micro-organisms, eventually associated with a superinfection by micetes. It has characterised by a deep oedema associated with lancinating pain and itching in external genitalia, rapidly evolves to perineal tissues necrosis and purulence. At this stadium patient's general conditions are still serious and patient may be comatose. When toxaemia is over, demarcation of necrotic areas can be remarkable and granulation start growing. Fournier's gangrene seems to be related to an ischemic necrosis caused by obliterative endoarteritis and thrombosis of internal pudendal and deep and superficial external pudendal artery. The infection gateway may be subcutaneous tissue lesion associated to trauma or surgical procedures in immunodeficient organism. Diagnosis is mainly clinical but a superficial ecography could be useful to demonstrate thickening in subcutaneous tissue with normal testicles. Both of them were middle aged males, heavy smokers, affected by hypertension and COPD. In both cases there was polymicrobial Gram positive bacterial infection. Antibiotic systemic therapy and topic therapy were administered. The patient also received hyperbaric oxygen therapy. Thirteen days after the admittance, the infection was defeated and we could start the surgical cover. To cover the scrotal wound we have used split-thickness skin grafts taken from the right thigh. These grafts took at 100% and the patient was discharged seven days after surgical operations. Follow-up at six months and at one year showed any functional limitation and a good aesthetic result.

Rupture of the cervix in a sulprostone induced abortion in the second trimester.

The authors report one case of cervical rupture in a normal uterus of a 43 years old second gravida, during an abortion at 16 weeks induced by sulprostone, a prostaglandin analogue. Case history and analysis of permittent condictions are listed. They conclude that uterus rupture remains an actual side effect of this prostaglandin E2 use, also when predisposing risk factors as scarred uterus, primigravid patients, age <20 years have been excluded, and gemeprost vaginal suppositories to ripen the cervix have been used.

Effect of EXP 3174 on blood pressure of normoreninemic renal hypertensive rats.

This study examined the effect on mean blood pressure of a new orally active nonpeptide angiotensin II (Ang II) receptor antagonist, EXP 3174, in doses that completely block exogenous Ang II action. Anesthetized and conscious two-kidney, two clip chronic renovascular hypertensive rats and sham-operated animals were used. In anesthetized hypertensive rats, intracerebroventricular administration of the inhibitor had no effect on blood pressure, whereas blood pressure was normalized by intravenous injection of the antagonist (163 +/- 12 to 110 +/- 9 mm Hg, P < .05). In sham anesthetized rats, intravenous injection of EXP 3174 also lowered blood pressure (112 +/- 6 to 96 +/- 6mm Hg, P < .05). In conscious rats, intravenous EXP 3174 induced a fall in pressure that was larger in hypertensive (156 +/- 9 to 132 +/- 5 mm Hg, P < .05) than in sham (104 +/- 3 to 94 +/- 4 mm Hg, P < .05) rats. Plasma renin activity was very high in anesthetized animals (hypertensive versus sham, 87.8 +/- 8.3 versus 95.7 +/- 10.2 ng Ang I/mL per hour); differences were not significant either between anesthetized hypertensive and sham or in conscious animals (hypertensive versus sham, 9.42 +/- 1.58 versus 6.74 +/- 2.32 ng Ang I/mL per hour). Angiotensinogen concentration was higher in cerebrospinal fluid in anesthetized hypertensive rats (36.4 +/- 3.0 versus 26.0 +/- 2.4 ng Ang I/mL, P < .05) and in the artery wall of hypertensive conscious rats (103.1 +/- 10.3 versus 75.2 +/- 7.8 ng Ang I/g, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Vasopressinergic mechanisms in the nucleus reticularis lateralis in blood pressure control.

We sought to determine whether arginine vasopressin (AVP) modulates arterial pressure (AP) by a receptor-mediated action in the nucleus reticularis rostroventrolateralis (nRVL). Immunocytochemical labeling with an antiserum against a synthetic AVP conjugate revealed a discrete although modest presumptive neuropeptidergic innervation of the nRVL. Electron microscopic analysis of vasopressinergic processes in the nRVL revealed that AVP-like immunoreactivity (AVP-LI) was primarily in axons and axon terminals. Immunoreactive terminals contained numerous small clear vesicles and large dense core vesicles and formed synapses with unlabeled dendrites. In the nRVL, retrograde transport-immunofluorescence data demonstrated close appositions between vasopressinergic beaded processes and a compact subambigual column of reticulospinal neurons labeled by deposits of cholera toxin beta-subunit into the thoracic spinal cord. Similar methods were used to define the origins of the AVP-afferent projection to nRVL. These retrograde transport-immunofluorescence studies demonstrated numerous retrogradely labeled neurons in the hypothalamus, including the paraventricular nucleus (PVN), after injections of a retrograde tracer, Fluoro-Gold into the ventrolateral medulla. However, double-labeled neurons were rare and confirmed a diffuse AVP afferent innervation of the sympathoexcitatory area. Microinjection of AVP into the nRVL in anesthetized rats produced a large dose-related increase in AP different from control at a dose of 1 pmol or higher. AVP injected intravenously elevated AP only at significantly higher doses. Microinjections of AVP into the nucleus tractus solitarii (NTS) had a smaller effect whereas into the caudal ventrolateral medulla exerted no effect on AP. Bilateral microinjections of an AVP antagonist, d(CH2)5[Tyr(Me)2]AVP into the nRVL produced no change in AP but blocked the increase produced by subsequent injections of AVP. An acute hemorrhage produced by withdrawal of 2 ml of blood from the femoral vein did not alter AP. However, bilateral microinjections of the AVP antagonist into the nRVL 5 min after hemorrhage decreased AP. In contrast, the AVP-antagonist injected intravenously after hemorrhage had no effect on AP. Our data suggest that under conditions demanding increased sympathetic drive to maintain AP, such as hemorrhage, a functional AVP receptor mechanism via terminals in the nRVL may be activated to restore normal levels of AP.