Multiparametric imaging guided HDR interventional radiotherapy (brachytherapy) boost in localized prostate cancer: a multidisciplinary experience.

OBJECTIVE: The aim of this study was to report a monoinstitutional multidisciplinary experience about the use of multiparametric imaging to identify the areas with higher risk of relapse in localized prostate cancer, with the purpose of allowing a biologically planned target dose escalation. PATIENTS AND METHODS: We performed a retrospective evaluation of patients diagnosed with prostate cancer who received treatments at our Interventional Oncology Center with interstitial interventional radiotherapy from 2014 to 2022. Inclusion criteria were histologically confirmed localized prostate cancer; and National Comprehensive Cancer Network (NCCN) risk class unfavorable intermediate or high/very high risk. The diagnostic work-up included multiparametric Magnetic resonance imaging (MRI), multiparametric Transrectal ultrasound (TRUS), Positron Emission Tomography Computed Tomography (PET-CT) with choline or PSMA (or alternatively bone scan). All patients were assessed and received one treatment with interstitial high-dose-rate interventional radiotherapy (brachytherapy) delivering external beam radiotherapy (46 Gy). All procedures were performed using transrectal ultrasound guidance under general anesthesia and the prescribed doses were 10 Gy to the whole prostate, 12 Gy to the peripheral zone and 15 Gy to the areas at risk. RESULTS: We report the data of 21 patients who were considered for the statistical analysis with a mean age of 62.5 years. The mean PSA nadir was 0.03 ng/ml (range 0-0.09). So far, no biochemical nor radiological recurrences have been recorded in our series. Regarding acute toxicity, the most commonly reported side effects were G1 urinary in 28.5% of patients and G2 urinary in 9.5%; all recorded acute toxicities resolved spontaneously. CONCLUSIONS: We present a real-life experience of biologically planned local dose escalation by interventional radiotherapy (brachytherapy) boost, followed by external beam radiotherapy in patients with intermediate unfavorable- or high/very high risk. The local control and the biochemical control rates are proved to be excellent and the toxicity profile tolerable.

Gender-specific effects of capsiate supplementation on body weight and bone mineral density: a randomized, double-blind, placebo-controlled study in slightly overweight women.

INTRODUCTION: Overweight and obesity are highly prevalent conditions associated with premature morbidity and mortality worldwide. Capsiate, a nonpungent analogue of capsaicin, binds to TRP vanilloid 1 (TRPV1) receptor, which is involved in adipogenesis, and could be effective as a weight-lowering agent. METHODS: Eighteen slightly overweight women were enrolled in this randomized, double-blind, placebo-controlled study. Nine patients were included in the capsiate intervention group and received 9 mg/day of capsinoids and 9 patients received placebo for 8 weeks. All patients underwent weight and waist circumference assessment before and after treatment. Body composition and bone mineral density (BMD) were also detected by dual-energy X-ray absorptiometry (DXA). RESULTS: Fourteen patients completed the study. The treatment with capsiate or placebo for 8 weeks was not associated with significant changes in weight or waist circumference. After treatment, there was a significant improvement in BMD values measured at the spine in the capsiate group (1.158 vs 1.106 g/cm2, + 4.7%; p = 0.04), but not in the group treated with placebo. Similarly, the capsiate group showed a 9.1% increase (p = 0.05) in the adipose tissue and an 8.5% decrease in lean mass measured at the supraclavicular level, whereas these changes were not statistically significant in the placebo group. CONCLUSIONS: Treatment with capsiate for 8 weeks led to negligible changes in body weight in a small sample of slightly overweight women, but our findings suggest a potential effect of capsaicin on bone metabolism in humans.

Modifiable and non-modifiable risk factors affecting walking recovery after hip fracture.

UNLABELLED: Modifiable and non-modifiable predictors of mobility recovery were analyzed on a sample of 774 hip fracture patients according to pre-fracture abilities. Overall predictors were mostly non-modifiable factors related to frailty of patients with the exception of 25-hydroxyvitamin D concentration which significantly affected walking recovery, especially in patients with higher pre-fracture performance. INTRODUCTION: This study aims to investigate mobility changes after hip fracture with the aim of identifying modifiable and non-modifiable predictors of mobility recovery according to different pre-fracture abilities. METHODS: This is a prospective inception cohort study of consecutive older patients, admitted with a fragility hip fracture in three Hospitals of Emilia Romagna (Italy). A sample of 774 patients alive at the sixth month was divided into three groups according to pre-fracture ambulation ability (group 1: mobile outdoors; group 2: mobile indoors; and group 3: mobile with help). The relationship between baseline characteristics of patients and the odds of walking recovery was analyzed using multivariate regression analysis. RESULTS: Mortality differed significantly among the three groups and was the highest in patients needing help to walk. Among the survivors, only 50.3 % of patients recovered walking ability. In a multivariate analysis, independent risk factors were different among the three groups. In group 1, older age, comorbidities, the use of walking devices before fracture, and low albumin level acted as negative factors while male gender, a pre-fracture high functional status, and higher 25-hydroxyvitamin D levels increased the probability of full recovery. In group 2, only pre-fracture functional status and 25-hydroxyvitamin D concentration were related to the recovery of walking ability. Pre-fracture functional status was also the only significant predictor for patients in group 3. CONCLUSIONS: Several baseline characteristics of patients are related to the likelihood of recovering walking ability after hip fracture. The 25-hydroxyvitamin D level seems to be the only relevant modifiable factor even if the effectiveness of its supplementation has yet to be demonstrated.

Diagnostic, therapeutic and healthcare management protocols in parathyroid surgery: II Consensus Conference of the Italian Association of Endocrine Surgery Units (U.E.C. CLUB).

AIM: To update the Diagnostic-Therapeutic-Healthcare Protocol (Protocollo Diagnostico-Terapeutico-Assistenziale, PDTA) created by the U.E.C. CLUB (Association of the Italian Endocrine Surgery Units) during the I Consensus Conference in 2008. METHODS: In the preliminary phase, the II Consensus involved a selected group of experts; the elaboration phase was conducted via e-mail among all members; the conclusion phase took place during the X National Congress of the U.E.C. CLUB. The following were examined: diagnostic pathway and clinical evaluation; mode of admission and waiting time; therapeutic pathway (patient preparation for surgery, surgical treatment, postoperative management, management of major complications); hospital discharge and patient information; outpatient care and follow-up. CONCLUSIONS: The PDTA for parathyroid surgery approved by the II Consensus Conference (June 2013) is the official PDTA of the U.E.C. CLUB.

Vitamin D supplementation is required to normalize serum level of 25OH-vitamin D in older adults: an observational study of 974 hip fracture inpatients.

BACKGROUND: Vitamin D deficiency is highly prevalent in older adults in all continents. In this study we assessed the vitamin D status of hip fracture subjects across different hospitals in a real word situation using the data from a multicenter cohort study on outcomes in orthogeriatric units. METHODS: We performed a prospective cohort study on 974 consecutive patients 75 yr or older admitted with fragility hip fracture over a 12 months period at 4 general hospitals of different districts in Emilia Romagna Region, Italy. Data collected included comorbidity, cognitive impairment, prefracture functional status, walking ability, living arrangement along with the use of antiosteoporotic drugs, serum intact PTH and serum 25-hydroxyvitamin D [25(OH)D]. RESULTS: Mean 25(OH)D serum levels were 12.2±9.4 ng/ml and 84.2% of patients had levels below recommended values. Male had a higher probability to have values within the reference range [odds ratio (OR): 1.74 (1.13-2.67); p=0.012] while living in nursing resulted negatively related even if only close to statistical significance [OR: 0.24 (0.06-1.02); p=0.051]. Vitamin D supplementation appeared to be the strongest factor associated with adequate level of vitamin D levels [OR: 4.50 (2.57-7.88); p<0.001). CONCLUSION: This study confirmed the very high rate of severe vitamin D deficiency in Italian subjects admitted with hip fracture. Our study also showed that supplementation of vitamin D is the strongest determinant influencing serum 25(OH)D level of older persons with hip fracture and these results should be taken into account when planning treatment in older persons.

[Spinal cord electric stimulation. Treatment of serious chronic ischemic syndromes of the limbs]. / La stimolazione elettrica del midollo spinale. Trattamento delle sindromi ischemiche croniche severe degli arti.

BACKGROUND: Aim of this study is to estimate the effectiveness of epidural electric stimulation of spinal cord for the treatment of patients with severe peripheral chronic arteriopathy who can't be surgically treated or when surgical therapy failed. METHODS: A retrospective study was carried out on 18 patients with peripheral chronic arteriopathy at clinical stage I of Fontaine classification; average age was of 60.08 years an they had rest pain and dystrophic lesions. Five patients couldn't be surgically treated. Stimulator catheter was placed in the epidural space and its action was evaluated studying lesion demarcation and pain resolution. RESULTS: In 16 cases there was a good pain control and in 14 patients lesion demarcation, while in 4 cases there was cases no improvement and amputation was necessary. CONCLUSIONS: Epidural electric stimulation of spinal cord is a valid treatment in selected patients for ischemia pain control and limb savage.

Spinal cord stimulation and cerebral blood flow in stroke: personal experience.

Spinal cord stimulation (SCS) can increase cerebral blood flow (CBF) and improve stroke patients. In order to better understand the haemodynamic changes underlining the clinical improvement, we have studied with transcranial Doppler (TCD), SPECT and NIRS 18 patients harbouring a stroke. SPECT Group: An increase of regional CBF during SCS was measured far from the stroke areas in 9 patients, further decrease in CBF was found in 2, no changes in 1. TCD Group: An increase of CBF velocities during SCS was found in 4 patients, no changes in 6, a decrease in 1. NIRS Group: Data consistent with and increase in CBF were obtained during SCS in the only patient undergone such a study. In 6 patients studied with different techniques, data obtained fitted only in 2 patients. In 3 patients no changes in TCD faced with changes in SPECT. In one case an improvement in TCD was evident in the left while an improvement of SPECT was shown in the right site. SCS is a valid therapeutic tool in stroke patient even if, as matter of fact, parallelism between clinical and haemodynamic changes during SCS is not demonstrated in our patients, rising the question on the role of ischemic penumbra in mediating clinical improvement.

Brain SPET and auditory cortex perfusion. Technical notes and preliminary results.

Auditory cortex stimulation was studied by 99Tcm-hexamethylpropyleneamine oxime (HMPAO) single photon emission tomography (SPET) in 11 patients with normal vestibular and auditory tests, as well as computed tomography. Markedly increased temporal and parietal blood flows were found in left brain cortex, contralateral to the stimulus. The right auditory areas showed moderate hyperactivity. The method might be useful for tonotopic mapping of auditory cortex, using various pure tonal stimuli.

Atrial natriuretic peptides are present throughout the plant kingdom and enhance solute flow in plants.

The present investigation was designed to 1) determine if atrial natriuretic-like peptides are present throughout the plant kingdom and 2) to determine if these peptides increase the flow of solute and/or water upward to leaves and flowers of plants. The 126-amino acid prohormone of atrial natriuretic factor (proANF)-(1-30), proANF-(31-67), and atrial natriuretic factor (ANF)-like peptides were present in the roots, stems, leaves, and flower petals of the more highly developed plants (Tracheophyta), with their highest concentrations being: Florida beauty > buddhist pine > Boston fern > rose = geranium = resurrection plant or club moss > Moses-in-the-cradle > Florida coontie. These peptides were also present in Bryophata (plants without vascular tissue or roots) and even in Euglena, flagellated chlorophyll-containing plants without leaves, stems, or roots. proANF-(1-30), proANF-(31-67), and proANF-(79-98) but not ANF (each at < 5.9 pg/ml) significantly increased (P < 0.001) the flow of colored water up stems, coloring their flowers 15-35 min earlier than the other one-half of the same flowers without exogenous peptide addition. These same peptides increased the rate of transpiration (i.e., loss of water from the leaves) and the absorption of solutions. High-performance gel permeation chromatography revealed that proANF-(1-30), proANF-(31-67), and ANF extracted from plants are very similar to their pure synthetic human sequences, with elution profiles and molecular weights of the plant extracts duplicating those of the pure synthetic peptides.

Acute effects of nifedipine, diltiazem and their combination in patients with chronic stable angina: a double-blind, randomized, cross-over, placebo-controlled study.

We evaluated the acute therapeutic effects of the oral administration of nifedipine (10 mg) and diltiazem (120 mg) alone and in combination in 16 patients with effort angina. The 16 patients (13 men and three women; mean age 59 +/- 7 years) performed a symptom-limited bicycle exercise stress test 3 h after placebo or active substance administration. Maximal work load, exercise duration and time to 1 mm ST segment depression were significantly increased and ST depression at peak exercise was significantly decreased by the combination of drugs. Nifedipine and diltiazem alone similarly improved exercise duration as markedly as their combination. One patient stopped the test after all three treatments for angina associated with ST depression > 2 mm. The combination of drugs yielded the best symptomatic effect: only four patients complained of angina in comparison to eight and seven patients after diltiazem and nifedipine, respectively. Nifedipine and diltiazem are effective and safe antianginal drugs. Some patients respond better to one drug than to the other. Patients who remain symptomatic in spite of maximal doses of a single drug may derive some benefit from combination therapy.

Nuclear estrogen receptor binding in microdissected brain regions of female rats during pregnancy: implications for maternal and sexual behavior.

Previously, we showed that changes in nuclear estrogen receptor (NER) concentrations within large dissections of the preoptic area and hypothalamus of pregnant rats might underlie changes in both maternal and sexual behaviors. To more precisely localize these biochemical changes, NER concentrations were measured in microdissected nuclei within the preoptic area and hypothalamus of pregnant rats on days 8, 16 and 22. Results indicated that NER levels changed significantly throughout pregnancy and that the magnitude and direction of change was site specific. Although a different pattern of change was found in each nucleus, NER levels in most preoptic area nuclei were significantly higher by the 16th day of pregnancy compared to those on day 8, while receptor levels in most hypothalamic nuclei did not increase until day 22 of pregnancy. The higher NER levels found in preoptic area nuclei of female rats as pregnancy advances can be correlated with growing maternal responsiveness during pregnancy, while elevated concentrations of NER in hypothalamic nuclei at the end of pregnancy may indicate preparation for postpartum estrus.

Cytosol and nuclear estrogen receptor binding in the preoptic area and hypothalamus of female rats during pregnancy and ovariectomized, nulliparous rats after steroid priming: correlation with maternal behavior.

In a previous study, high nuclear estrogen receptor concentrations in the preoptic area (POA) were found on Day 16 of pregnancy to prime females to respond to a subsequent low dose of estradiol benzoate (EB) after hysterectomy-ovariectomy by exhibiting maternal behavior in 48 hr. Receptor concentrations in the POA were found to be higher than those in the hypothalamus (HYP). The present study investigated when nuclear estrogen receptors increase during pregnancy in POA and when the difference in receptor concentrations between POA and HYP occurs. An attempt was made to reproduce these pregnancy changes with a 16-day treatment of estrogen and progesterone in ovariectomized (OVX), nulliparous rats. In Experiment 1, we measured cytosol and nuclear estrogen receptor concentrations in the POA and HYP of female rats during pregnancy. Nuclear receptor concentrations in the POA increased beginning on Day 10, increased again on Day 16, and continued at this high level for the remainder of pregnancy. Nuclear estrogen receptor concentrations in the HYP remained at a lower level throughout most of pregnancy until Day 22 when they increased significantly. In Experiment 2, we tested the maternal behavior and measured estrogen receptor concentrations in OVX, steroid-primed, nulliparous rats after hysterectomy (H) and EB treatment. While 90% of estradiol (E) + progesterone (P)-primed females displayed short-latency maternal behavior 48 hr after H and EB treatment, 46% of E + vehicle (V)-treated controls were maternal. At 0 hr (prior to H and EB treatment), there was a significantly larger nuclear receptor accumulation in the POA but significantly attenuated receptor binding in the HYP. P treatment significantly affected cytosol and nuclear estrogen receptor dynamics. Differences in nuclear estrogen receptor concentrations were shown to be based on the number of available binding sites and not to changes in receptor affinity for estradiol.

Nuclear estrogen receptor binding in the preoptic area and hypothalamus of pregnancy-terminated rats: correlation with the onset of maternal behavior.

Terminating the pregnancies of female rats on day 16 (D 16) by hysterectomy and ovariectomy (HO) and administering estradiol benzoate (EB) systemically or centrally into the medial preoptic area (MPOA) stimulates the onset of maternal behavior 48 h later. Since estrogen's effects are mediated through its intracellular receptors, the present studies measured nuclear and cytosol estrogen receptor concentrations in the POA and hypothalamus (HYP) of female rats during the 48 h when estrogen is active in stimulating maternal behavior. A low dose of EB (5 micrograms/kg) was used which was effective in stimulating maternal behavior in D16HO females but not in nonpregnant HO females of two types. In D16 animals there was a significantly higher concentration of nuclear receptors in the POA than in the HYP at time 0 (before HO and EB) but thereafter levels were similar in the two areas: nuclear receptor levels rose between 6 and 24 h after which they declined. In nonpregnant females, nuclear receptor levels at time 0 were low in both brain regions, rose significantly between 0 and 24 h, and significantly declined between 24 and 48 h similar to the D16 females. There were minimal differences in cytosol receptor levels among all groups at any time. Results from additional groups, nonpregnant HO females given 100 micrograms/kg EB and D16H animals (females whose pregnancies were terminated by hysterectomy only and their ovaries left intact), both of which exhibit maternal behavior at 48 h, support the idea that a high level of nuclear estrogen receptors in the POA followed by a sustained high level is necessary for estrogen stimulation of maternal behavior.

[Aztreonam and aminoglycosides in the therapy of urinary infections associated with renal calculosis]. / Aztreonam e aminoglicosidi nella terapia delle infezioni urinarie associate a calcolosi renale.

Renal calculosis associated with urinary tract infections due to urease-positive or -negative microorganisms poses difficult therapeutic problems. The introduction of monobactam antibiotics such as aztreonam offers a valid therapeutic alternative thanks to the action of this drug on the gram-negative organism often at the root of these infections. The above study has been carried out in 10 patients with infections due to organisms sensitive to aztreonam and aminoglucosides. Treatment with aztreonam (1 g i.m. 3 times daily) brought about sterilization lasting from 3 weeks to permanently in 5 cases. In one case sterilization was transitory and in 4 cases treatment was unsuccessful. Creatinine blood level and other biochemical parameters did not vary. Aminoglucosides alone brought about transitory sterility in 2 cases and was unsuccessful in 6. At the end of treatment, creatinine blood level had increased significantly. Given the absence of toxicity the definitely better therapeutic result, and the absence of induced resistance, aztreonam should be considered the drug of choice and should be preferred to aminoglucosides for the management of urinary tract infections due to microorganisms sensitive to both types of drugs in patients with urinary calculosis.