A pilot trial of RNS60 in amyotrophic lateral sclerosis.

Introduction: RNS60 is a novel immune-modulatory agent that has shown neuroprotective effects in amytrophic lateral sclerosis (ALS) preclinical models. RNS60 is administered by weekly intravenous infusion and daily nebulization. The objective of this pilot open-label trial was to test the feasibility, safety, and tolerability of long-term RNS60 administration in ALS patients.

Gender influence on professional satisfaction and gender issue perception among young oncologists. A survey of the Young Oncologists Working Group of the Italian Association of Medical Oncology (AIOM).

Background: The professional gender gap is increasingly recognised in oncology. We explored gender issues perception and gender influence on professional satisfaction/gratification among young Italian oncologists.

Methods: Italian oncologists aged ≤40 years and members of the Italian Association of Medical Oncology were invited to participate in an online survey addressing workload/burnout, satisfaction in professional abilities and relations, relevant factors for professional gratification, and gender barriers.

Neurologic outcome of postanoxic refractory status epilepticus after aggressive treatment.

Objective: To investigate neurologic outcome of patients with cardiac arrest with refractory status epilepticus (RSE) treated with a standardized aggressive protocol with antiepileptic drugs and anesthetics compared to patients with other EEG patterns.

Methods: In the prospective cohort study, 166 consecutive patients with cardiac arrest in coma were stratified according to 4 independent EEG patterns (benign, RSE, generalized periodic discharges [GPDs], malignant nonepileptiform) and multimodal prognostic indicators. Primary outcomes were survival and cerebral performance category (CPC) at 6 months.

Best practices for the management of thymic epithelial tumors: A position paper by the Italian collaborative group for ThYmic MalignanciEs (TYME).

Thymic epithelial tumors (TETs) are a heterogenous group of rare tumors, with a complex histopatological classification. Furthermore, the recent introduction of the first TNM staging system, that is scheduled to replace the Masaoka-Koga system, may create further difficulties in TET management, that remains challenging. Several guidelines for treatment of TETs are available and provide recommendations based mainly on non randomized trials and retrospective or limited series.

PERK inhibition attenuates the abnormalities of the secretory pathway and the increased apoptotic rate induced by SIL1 knockdown in HeLa cells.

Loss-of-function mutations in the SIL1 gene are linked to Marinesco-Sjögren syndrome (MSS), a rare multisystem disease of infancy characterized by cerebellar and skeletal muscle degeneration. SIL1 is a ubiquitous adenine nucleotide exchange factor for the endoplasmic reticulum (ER) chaperone BiP. The complexity of mechanisms by which loss of SIL1 causes MSS is not yet fully understood.

A phase II randomised (calibrated design) study on the activity of the single-agent trabectedin in metastatic or locally relapsed uterine leiomyosarcoma.

Background: Patients with recurrent/metastatic uterine leiomyosarcoma (U-LMS) have a dismal prognosis. This phase II study aims to evaluate trabectedin efficacy and safety in advanced U-LMS.

Methods: Eligible patients had received ≥ one line of chemotherapy.

RELEVENT Trial: Phase II Trial of Ramucirumab, Carboplatin, and Paclitaxel in Previously Untreated Thymic Carcinoma/B3 Thymoma With Area of Carcinoma.

Thymic epithelial tumors are rare malignancies. Thymic carcinoma represents about 20% of all thymic epithelial tumors and has aggressive behavior, with a greater tendency to metastatic spread. Thymic carcinoma is often diagnosed in advanced stages for which systemic treatment is the main therapeutic option.

Prevalence, characteristics and treatment of chronic pain in elderly patients hospitalized in internal medicine wards.

Background: Chronic pain is a frequent characteristic of elderly people and represents an actual and still poorly debated topic.

Objective: We investigated pain prevalence and intensity, and its pharmacological therapy in elderly patients hospitalized in 101 internal medicine wards.

Methods: Taking advantage of the "REgistro POliterapie Società Italiana Medicina Interna" (REPOSI), we collected 2535 patients of whom almost a quarter was older than 85 years old.

Group I Paks support muscle regeneration and counteract cancer-associated muscle atrophy.

Background: Skeletal muscle is characterized by an efficient regeneration potential that is often impaired during myopathies. Understanding the molecular players involved in muscle homeostasis and regeneration could help to find new therapies against muscle degenerative disorders. Previous studies revealed that the Ser/Thr kinase p21 protein-activated kinase 1 (Pak1) was specifically down-regulated in the atrophying gastrocnemius of Yoshida hepatoma-bearing rats.

Epilepsy.

Epilepsy affects all age groups and is one of the most common and most disabling neurological disorders. The accurate diagnosis of seizures is essential as some patients will be misdiagnosed with epilepsy, whereas others will receive an incorrect diagnosis. Indeed, errors in diagnosis are common, and many patients fail to receive the correct treatment, which often has severe consequences.

PERK inhibition delays neurodegeneration and improves motor function in a mouse model of Marinesco-Sjögren syndrome.

Marinesco-Sjögren syndrome (MSS) is a rare, early onset, autosomal recessive multisystem disorder characterized by cerebellar ataxia, cataracts and myopathy. Most MSS cases are caused by loss-of-function mutations in the gene encoding SIL1, a nucleotide exchange factor for the molecular chaperone BiP which is essential for correct protein folding in the endoplasmic reticulum. Woozy mice carrying a spontaneous Sil1 mutation recapitulate key pathological features of MSS, including cerebellar atrophy with degeneration of Purkinje cells and progressive myopathy.

Safety and efficacy of preoperative or postoperative chemotherapy for resectable pancreatic adenocarcinoma (PACT-15): a randomised, open-label, phase 2-3 trial.

Background: Pancreatic ductal adenocarcinoma are known to metastasise early and a rationale exists for the investigation of preoperative chemotherapy in patients with resectable disease. We aimed to assess the role of combination chemotherapy in this setting in the PACT-15 trial.

Methods: We did this randomised, open-label, phase 2-3 trial in ten hospitals in Italy.

Duration of Adjuvant Chemotherapy for Stage III Colon Cancer.

Background: Since 2004, a regimen of 6 months of treatment with oxaliplatin plus a fluoropyrimidine has been standard adjuvant therapy in patients with stage III colon cancer. However, since oxaliplatin is associated with cumulative neurotoxicity, a shorter duration of therapy could spare toxic effects and health expenditures.

Methods: We performed a prospective, preplanned, pooled analysis of six randomized, phase 3 trials that were conducted concurrently to evaluate the noninferiority of adjuvant therapy with either FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine and oxaliplatin) administered for 3 months, as compared with 6 months.

Anthracycline-induced cardiotoxicity: A multicenter randomised trial comparing two strategies for guiding prevention with enalapril: The International CardioOncology Society-one trial.

Background: Troponin changes over time have been suggested to allow for an early diagnosis of cardiac injury ensuing cancer chemotherapy; cancer patients with troponin elevation may benefit of therapy with enalapril. It is unknown whether a preventive treatment with enalapril may further increase the benefit.

Methods: The International CardioOncology Society-one trial (ICOS-ONE) was a controlled, open-label trial conducted in 21 Italian hospitals.

Shifting from Oral Contraceptives to Norethisterone Acetate, or Vice Versa, because of Drug Intolerance: Does the Change Benefit Women with Endometriosis?

Background/aims: Oral contraceptives (OC) and norethisterone acetate (NETA) are among first-line medical therapies for symptomatic endometriosis, but their use is sometimes associated with intolerable side effects. We investigated whether shifting from low-dose OC to NETA (2.5 mg/day), or vice versa, improved tolerability.

Neuroinflammation Alters Integrative Properties of Rat Hippocampal Pyramidal Cells.

Neuroinflammation is consistently found in many neurological disorders, but whether or not the inflammatory response independently affects neuronal network properties is poorly understood. Here, we report that intracerebroventricular injection of the prototypical inflammatory molecule lipopolysaccharide (LPS) in rats triggered a strong and long-lasting inflammatory response in hippocampal microglia associated with a concomitant upregulation of Toll-like receptor (TLR4) in pyramidal and hilar neurons. This, in turn, was associated with a significant reduction of the dendritic hyperpolarization-activated cyclic AMP-gated channel type 1 (HCN1) protein level while Kv4.

Axonal transport in a peripheral diabetic neuropathy model: sex-dimorphic features.

Background: Disruption of axonal transport plays a pivotal role in diabetic neuropathy. A sex-dimorphism exists in the incidence and symptomatology of diabetic neuropathy; however, no studies so far have addressed sex differences in axonal motor proteins expression in early diabetes as well as the possible involvement of neuroactive steroids. Interestingly, recent data point to a role for mitochondria in the sexual dimorphism of neurodegenerative diseases.

Targeting melanoma stem cells with the Vitamin E derivative δ-tocotrienol.

The prognosis of metastatic melanoma is very poor, due to the development of drug resistance. Cancer stem cells (CSCs) may play a crucial role in this mechanism, contributing to disease relapse. We first characterized CSCs in melanoma cell lines.

Is Shifting to a Progestin Worthwhile When Estrogen-Progestins Are Inefficacious for Endometriosis-Associated Pain?

The purpose of this study was to assess the proportion of patients satisfied with their treatment after a change from a low-dose oral contraceptive (OC) to norethisterone acetate (NETA) because of inefficacy of OC on pain symptoms. To this end, prospective, self-controlled study was conducted on 153 women using OC as a treatment for endometriosis and with persistence of one or more moderate or severe pain symptoms. At baseline and during 12 months after a shift from OC to oral NETA, 2.

Fibronectin glomerulopathy - A sporadic case with unusual clinical manifestation.

A 22-year-old nondiabetic young Indian female presented with short history of dyspnea, anorexia, and bilateral leg swelling. Her laboratory evaluation showed severe anemia, serum creatinine of 11.89 mg/dL, nephrotic range proteinuria and microscopic hematuria with 6-8 red blood cell/high-power field.

Medical treatment or surgery for colorectal endometriosis? Results of a shared decision-making approach.

Study Question: What is the degree of patient satisfaction in women with symptomatic colorectal endometriosis who choose medical or surgical treatment after a shared decision-making (SDM) process?

Summary Answer: The degree of satisfaction with treatment was high both in women who chose medical treatment with a low-dose oral contraceptive (OCP) or a progestin, and in those who chose to undergo surgical resection of bowel endometriosis.

What Is Known Already: Hormonal therapies and surgery for colorectal endometriosis have been investigated in non-comparative studies with inconsistent results.

Study Design, Size, Duration: Parallel cohort study conducted on 87 women referring to our centre with an indication to surgery for colorectal endometriosis.

The prognostic role of tumor size in early breast cancer in the era of molecular biology.

Background: The prognosis of early breast cancer (EBC) depends on patient and tumor characteristics. The association between tumor size, the largest diameter in TNM staging, and prognosis is well recognized. According to TNM, tumors classified as T2, could have very different volumes; e.

Inhibition of monoacylglycerol lipase terminates diazepam-resistant status epilepticus in mice and its effects are potentiated by a ketogenic diet.

Objective: Status epilepticus (SE) is a life-threatening and commonly drug-refractory condition. Novel therapies are needed to rapidly terminate seizures to prevent mortality and morbidity. Monoacylglycerol lipase (MAGL) is the key enzyme responsible for the hydrolysis of the endocannabinoid 2-arachidonoylglycerol (2-AG) and a major contributor to the brain pool of arachidonic acid (AA).