Radiotherapy and combination chemotherapy with carmustine,vincristine, and procarbazine (BVP) in primary brain tumors

Summary 26 patients with astrocytoma grade 11–111, and 36 with malignant glioma (astrocytoma grade IV or glioblastoma) were submitted three days after surgery to a cycle of combination chemotherapy, including BCNU, VCR, PCZ (BVP). Eighteen days after surgery, patients received 40 Gy (astrocytoma grade 11–111) or 45 Gy (malignant glioma) of megavoltage whole-brain irradiation, with an additional boost to the tumor bed of 20 Gy, delivered in 6 weeks. Vincristine was injected weekly during radiotherapy. At the end of radiotherapy, patients received BVP every 6 weeks for at least 8 cycles or until a recurrence or progressive disease. Performance status of grade 1 or 2 was achieved in 15 (60%) and in 5 (20%), respectively, of patients with astrocytoma grade 11–111 after 6 months, and in 6 ps. (29%) and in 9 ps. (42%) after 12 months of follow-up. Only 2 (5.5%) and 18 (64%) patients with malignant glioma achieved a performance status of grade 1 or 2 after 6 months, and these proportions are 6% and 35%, respectively, after 12 months. After a 5-year follow-up, 59% of patients with astrocytoma are still alive, with a median survival time of 60+ months, whereas only 4% of patients with malignant glioma are alive, with a median of 11.2 months.     

Metabolic fate of zetidoline,a new neuroleptic agent,in man

Summary Healthy volunteers administered orally a single dose (20 mg) of [2-¹⁴C]zetidoline, a new dopamine antagonist, exhibited rapid absorption of radioactivity with peak plasma levels of 250–300 ng/ml achieved in 1 h. The compound underwent intensive metabolic first-pass so that plasma radioactivity was represented mostly by two products, metabolite B endowed with neuroleptic activity, and metabolite D inactive, while unchanged zetidoline was not detected. Disappearance of radioactivity from plasma was rapid with a half-life of 1.78±0.20 h.The simultaneous assay of plasma prolactin showed increased levels of the hormone (+464% at the peak time) up to the 6th h after dosing, with plasma concentration profile which mimic those of metabolite B.The radioactive test-dose was eliminated mainly via the kidneys with an average urinary recovery of 84.7±1.7% in 4 days (73.4±1.1% within 8 h). The main urinary metabolite (metabolite G) and two minor ones (metabolites B and D) were purified and their structures assigned by IR, MS and NMR spectroscopy, they are: 1-(3-chloro-4-hydroxyphenyl)-3[2-(3,3-dimethyl-1-azetidinyl)ethyl]imidazolidin-2-one, metabolite B; 1-[2-(3,3-dimethyl-1-azetidinyl)ethyl]imidazolidin-2-one, metabolite D and the 4-O-sulphate ester of metabolite B, metabolite G.The metabolic fate of zetidoline in man follows the same phase I reactions demonstrated in rats and dogs, while the phase II reaction is sulphoconjugation instead of the glucuronidation observed in animals.     

The Nutraceutical N-Palmitoylethanolamide (PEA) Reveals Widespread Molecular Effects Unmasking New Therapeutic Targets in Murine Varicocele

Varicocele is an age-related disease with no current medical treatments positively impacting infertility. Toll-like receptor 4 (TLR4) expression is present in normal testis with an involvement in the immunological reactions. The role of peroxisome proliferator-activated receptor-α (PPAR-α), a nuclear receptor, in fertility is still unclear. N-Palmitoylethanolamide (PEA), an emerging nutraceutical compound present in plants and animal foods, is an endogenous PPAR-α agonist with well-demonstrated anti-inflammatory and analgesics characteristics. In this model of mice varicocele, PPAR-α and TLR4 receptors’ roles were investigated through the administration of ultra-micronized PEA (PEA-um). Male wild-type (WT), PPAR-α knockout (KO), and TLR4 KO mice were used. A group underwent sham operation and administration of vehicle or PEA-um (10 mg/kg i.p.) for 21 days. Another group (WT, PPAR-α KO, and TLR4 KO) underwent surgical varicocele and was treated with vehicle or PEA-um (10 mg/kg i.p.) for 21 days. At the end of treatments, all animals were euthanized. Both operated and contralateral testes were processed for histological and morphometric assessment, for PPAR-α, TLR4, occludin, and claudin-11 immunohistochemistry and for PPAR-α, TLR4, transforming growth factor-beta3 (TGF-β3), phospho-extracellular signal-Regulated-Kinase (p-ERK) 1/2, and nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) Western blot analysis. Collectively, our data showed that administration of PEA-um revealed a key role of PPAR-α and TLR4 in varicocele pathophysiology, unmasking new nutraceutical therapeutic targets for future varicocele research and supporting surgical management of male infertility.     

In Vivo Observation of Cutaneous Larva Migrans by Fluorescence-Advanced Videodermatoscopy

Fluorescence-advanced videodermatoscopy is not a widespread diagnostic technique. Its application in dermatology can facilitate the diagnosis of diseases such as cutaneous larva migrans by enabling us to recognize the precise position of larva in vivo on the skin. Using this noninvasive technique, we detected a case of cutaneous larva migrans in a patient.     

Primary versus revision implant for inflatable penile prosthesis: A propensity score-matched comparison

Inflatable penile prosthesis (IPP) provides excellent outcomes after virgin implants. However, few data on IPP after revision surgery are available. This study aimed at comparing the outcomes of IPP in patients undergoing primary or revision implant surgery. Patients who underwent revision implant surgery (Group 1) between 2013 and 2020 were identified. Overall, 20 patients (Group 1) could be matched with a contemporary matched pair cohort of surgery-naive patients (Group 2) in a 1:1 ratio. Patients in Group 2 had a significantly shorter operative time [median (IQR): 84 (65–97) vs. 65 (51–75) min; p = .01] and lower rate of overall complications (25% vs. 10%; p = .01). Of note, mean (SD) scores for the Quality of Life and Sexuality with Penile Prosthesis (QoLSPP) questionnaire demonstrated high satisfaction and IPP efficacy in both Groups 1 and 2: functional domain [3.9 (1.0) vs. 4.0 (1.2); p = .4], personal [3.9 (1.1) vs. 4.0 (1.1); p = .3], relational [3.8 (1.3) vs. 3.9 (1.1); p = .5] and social [3.9 (1.1) vs. 4.0 (1.2); p = .2]. These results suggest that in experienced hands, IPP offers high satisfaction to both patients and partners even in the setting of revision implant. However, it is mandatory to inform those patients about the increased risk of perioperative complications.     

The role of external ventricular drainage for the management of posterior cranial fossa tumours: a systematic review

Neurosurgical Review - Posterior cranial fossa tumours frequently develop hydrocephalus as first presentation in up to 80% of paediatric patients and 21.4% of adults, although it resolves after...     

The role of multiparametric MRI in active surveillance for low-risk prostate cancer: The ROMAS randomized controlled trial

BackgroundWe aim to evaluate the impact of multiparametric magnetic resonance imaging and fusion-target biopsy for early reclassification of patients with low-risk Prostate Cancer in a randomized trial.Materials and methodsBetween 2015 and 2018, patients diagnosed with Prostate Cancer after random biopsy fulfilling PRIAS criteria were enrolled and centrally randomized (1:1 ratio) to study group or control group. Patients randomized to study group underwent multiparametric magnetic resonance imaging at 3 months from enrollment: patients with positive findings (PIRADS-v2>2) underwent fusion-target biopsy; patients with negative multiparametric magnetic resonance imaging or confirmed ISUP - Grade Group 1 at fusion-target biopsy were managed according to PRIAS schedule and 12-core random biopsy was performed at 12 months. Patients in control group underwent PRIAS protocol, including a confirmatory 12-core random biopsy at 12 months. Primary endpoint was a reduction of reclassification rate at 12-month random biopsy in study group at least 20% less than controls. Reclassification was defined as biopsy ISUP Grade Group 1 in >2 biopsy cores or disease upgrading.ResultsA total of 124 patients were randomized to study group (n = 62) or control group (n = 62). Around 21 of 62 patients (34%) in study group had a positive multiparametric magnetic resonance imaging, and underwent fusion-target biopsy, with 11 (17.7%) reclassifications. Considering the intention-to-treat population, reclassification rate at 12-month random biopsy was 6.5% for study group and 29% for control group, respectively (P < 0.001).ConclusionsThe early employment of multiparametric magnetic resonance imaging for active surveillance patients enrolled after random biopsy consents to significantly reduce reclassifications at 12-month random biopsy.     

Nocturnal Paroxysmal Dystonia with Short-Lasting Attacks: Three Cases with Evidence for an Epileptic Frontal Lobe Origin of Seizures

The epileptic or nonepileptic origin of nocturnal paroxysmal dystonia (NPD) has been debated. We studied three patients with frequent attacks during non-REM sleep. During prolonged video-EEG monitoring, two patients had a convulsive seizure after a typical NPD episode and on these occasions EEG showed epileptiform discharge. In the three patients, attacks occurred repeatedly with different intensity, representing "fragments" of the same seizure. These fragments of the attack could occur periodically every 20-40 s. We postulate that short NPD attacks are actually epileptic seizures originating from the frontal lobes. The rhythmicity of the episodes may be due to rhythmic oscillation of cortical function during non-REM sleep.