Coupling motor evoked potentials and brain [18F]FDG-PET in Amyotrophic Lateral Sclerosis: preliminary findings on disease severity.

BACKGROUND: The diagnosis of amyotrophic lateral sclerosis (ALS) is primarily clinical, supported by the electromyographic examination to reveal signs of lower motor neuron damage. Identifying reliable markers of upper motor neuron (UMN) involvement is challenging. On this regard, the role of transcranial magnetic stimulation-induced motor-evoked potentials (TMS-MEPs), and its relationship with UMN burden, is still under investigation. OBJECTIVE: To evaluate the ability of TMS-MEPs in delineating the neurophysiological UMN damage, and to determine the relationship between TMS-MEPs and [18F]FDG-PET measures of neural dysfunction. METHODS: We retrospectively selected 13 ALS patients who underwent, during the diagnostic process, the TMS-MEPs and [18F]FDG-PET scans. Demographic and clinical data were collected. For the MEP evaluation, we considered normal MEP, absent MEP, or significantly increased central-motor-conduction-time. For [18F]FDG-PET, we conducted voxel-wise analyses, both at single-subject and group levels, exploring hypometabolism and hypermetabolism patterns in comparison with a large dataset of healthy controls (HC). RESULTS: Based on TMS-MEPs, we identified 4/13 patients with normal MEP in all limbs (GROUP-NO), while 9/13 had an abnormal MEP in at least one limb (GROUP-AB). Despite the [18F]FDG-PET single-subject analysis revealed heterogenous expression of regional hypo- and hyper-metabolism patterns in the patients, the group-level analysis revealed a common hypometabolism, involving the precentral gyrus and the supplementary motor area, the paracentral lobule and the anterior cingulate cortex in the GROUP-AB. Moreover, exclusively for the GROUP-AB compared with HC, a relative hypermetabolism was observed in the right cerebellum, right inferior and middle temporal gyrus. The GROUP-NO showed no specific cluster of hypo- and hyper-metabolism compared to HC. CONCLUSION: This study showed altered brain metabolism only in the ALS group with abnormal MEPs, suggesting an association between the two biomarkers in defining the UMN damage.

Spectro-acoustic voice parameters in transoral laser microsurgery vs exclusive radiotherapy for early-stage glottic carcinoma: A systematic review and meta-analysis.

PURPOSE: In early glottic squamous cell carcinoma, similar results have been described in terms of disease control between transoral laser microsurgery (TLM) and radiation therapy (RT). During the past two decades, several studies compared subjective vocal outcomes of exclusive RT with those of TLM, showing a trend towards improving results for TLM over time. However, the objective differences in terms of spectro-acoustic voice parameters between exclusive RT and TLM have been less frequently investigated. The aim of this systematic review with meta-analysis was to evaluate voice quality after TLM and RT treatment for early glottic carcinoma, based on acoustic analysis parameters including jitter, shimmer, noise to harmonic ratio, fundamental frequency and maximum phonation time. MATERIAL AND METHODS: A search of the English published literature was conducted on the Pubmed, Scopus and Cochrane databases following PRISMA guidelines. RESULTS: A total of 441 titles were retrieved from the search. After full-text screening and application of inclusion/exclusion criteria, 12 articles were included. We found no significant differences between TLM and RT treatment in the considered acoustic analysis parameters, except for Shimmer, with more favorable values reported in the RT group. CONCLUSIONS: Considering the spread of the disease and expecting an improvement in long-term survival over time, well-designed and multicentric studies involving larger populations with a long-term follow up are mandatory to better assess objective voice outcomes in terms of spectro-acoustic voice parameters.

Audiological Phenotypes of Connexin Gene Mutation Patterns: A Glance at Different GJB2/GJB6 Gene Mutation Profiles.

GJB2 mutations are the most common cause of autosomal-recessive non-syndromic sensorineural hearing loss (SNHL). The available evidence shows large phenotypic variability across different genotypes and allelic variants. The aim of this study was to investigate the clinical and audiological features of a cohort of subjects with different GJB2/GJB6 gene mutation profiles from a tertiary referral center in Northeastern Italy. We considered 57 patients with GJB2/GJB6 mutations presenting with congenital, non-syndromic SNHL, mainly coming from the Veneto region (Italy). The samples were screened for mutations in exons 1 and 2 of the GJB2 gene and for the GJB6 gene deletion del (GJB6-D13S1830). Free-field and air-conduction frequency-specific thresholds and the pure-tone average (PTA) were considered in the statistical analysis. Five patients (8.87%) had connexin gene mutations in simple heterozygosis, 15 (26.31%) in compound heterozygosis, 34 (59.64%) in homozygosis, and 3 (5.26%) with digenic patterns. The frequency-specific air-conduction thresholds showed significantly different mean values across the different genotypes (Roy's largest-root test, p = 0.0473). Despite the evidence already available on genetic SNHL, many new insights are to be expected. Further large-scale prospective studies including different populations are necessary to confirm these preliminary findings about the clinical and audiological features of patients with different GJB2/GJB6 gene mutation patterns.

Preservation of Distortion Product Otoacoustic Emissions in OTOF -Related Hearing Impairment.

OBJECTIVES: Attenuation of otoacoustic emissions over time has been reported for many patients with hearing impairment harboring mutations in the OTOF gene. In this study, the time course of changes of distortion product otoacoustic emissions (DPOAEs) has been analyzed in a cohort of patients in the light of tympanometry results. DESIGN: The changes of DPOAEs in 16 patients with OTOF -related hearing impairment were retrospectively analyzed. RESULTS: All but one subject showed DPOAEs bilaterally at the time of diagnosis. Three patients diagnosed as adults still had DPOAEs at ages of 27, 31, and 47 years, respectively. Follow-up was available for 7 children diagnosed at the age of 1 to 3 years, who still showed preservation of DPOAEs at ages of 5 to 16 years. The responses were absent or attenuated in amplitude at some follow-up appointments in association with type B or C tympanograms. CONCLUSIONS: DPOAEs are preserved much longer than expected in a cohort of patients with OTOF -related hearing impairment. The previously reported loss of DPOAEs may have been caused in some children by increased middle ear impedance due to otitis media.

What is the landscape of evidence about the safety of physical agents used in physical medicine and rehabilitation? A scoping review.

BACKGROUND: Several systematic reviews (SRs) assessing the effectiveness of superficial physical agents have been published, but the evidence about their safety remains controversial. OBJECTIVE: To identify areas where there is evidence of the safety of physical agents by a scoping review. DESIGN: Four databases were systematically searched for including English SRs that explored and reported safety in terms of adverse events (AEs) related to the application of physical agents in outpatient and inpatient physical medicine and rehabilitation settings managed by healthcare professionals, published in January 2011-29 September 2021. The severity of AEs was classified according to the Common Terminology Criteria. Then, AE findings were summarised according to the SR syntheses. Finally, the reporting of the certainty of the evidence was mapped. RESULTS: Overall, 117 SRs were retrieved. Most of the SRs included randomised controlled trials (77%) and patients with musculoskeletal disorders (67%). The most investigated physical agents were extracorporeal shock wave therapy (ESWT) (15%), transcutaneous electrical nerve stimulation (13%) and electrical stimulation (12%). No AE (35%) was reported in one-third of the included primary studies in SRs, whereas few severe AEs occurred in less than 1% of the sample. Among physical agents, ESWT showed an increased risk of experiencing mild AEs compared with the control. Most SRs reported a qualitative AE synthesis (65.8%), and few reported the certainty of the evidence (17.9%), which was mainly low. CONCLUSION: We found evidence of safety on several physical agents coming mostly from qualitative synthesis. No significant harms of these interventions were found except for ESWT reporting mild AEs. More attention to the AEs reporting and their classification should be pursued to analyse them and assess the certainty of evidence quantitatively. REVIEW REGISTRATION: https://osf.io/6vx5a/.

Depression and Anxiety Are Associated With Worse Subjective and Functional Baseline Scores in Patients With Frozen Shoulder Contracture Syndrome: A Systematic Review.

Purpose: To investigate whether psychological factors, such as avoidance behavior, fear, pain catastrophization, kinesiophobia, anxiety, depression, optimism, and expectation are associated with different subjective and functional baseline scores in patients with frozen shoulder contracture syndrome (FSCS). Methods: Searches were conducted in MEDLINE, Cochrane Library (CENTRAL Database), PEDro, Pubpsych, and PsychNET.APA without restrictions applied to language, date, or status of publication. Two authors reviewed study titles, abstract, and full text based on the following inclusion criteria: adult population (≥ 30 < 70 years old) with FSCS. Results: Seven hundred and seventy-six records were included by the search strategies. After title final screening, 6 studies were included for the qualitative synthesis. Psychological features investigated were anxiety, depression, pain-related fear, pain catastrophizing, and pain self-efficacy; reported outcomes included pain, function, disability, quality of life, and range of motion. Data suggest that anxiety and depression impact self-assessed function, pain, and quality of life. There is no consensus on the correlation between psychological variables and range of motion. Associations were suggested between pain-related fear, pain-related beliefs, and pain-related behavior and perceived arm function; pain-related conditions showed no significant correlation with range of motion and with perceived stiffness at baseline. Conclusion: Scores traditionally thought to assess physical dimensions like shoulder pain, disability, and function seem to be influenced by psychological variables. In FSCS patients, depression and anxiety were associated with increased pain perception and decreased function and quality of life at baseline. Moreover, pain-related fear and catastrophizing seem to be associated with perceived arm function.

Tinnitus following COVID-19 vaccination: report of three cases.

OBJECTIVE: To ensure the safety and quality of vaccines, especially the newest RNA-vaccines against COVID-19, is one of the World Health Organization's current highest priorities. DESIGN: Case description. STUDY SAMPLE: We report three cases of sudden unilateral tinnitus following BNT162b2 mRNA-vaccine injection, which rapidly resolved in 2 out of 3 cases. RESULTS: The mechanism responsible for its development remains unclear. A hypersensitivity reaction with an abnormal autoimmune response or a vasculitic event may be implicated. CONCLUSIONS: Large-scale and well-designed studies are needed to improve surveillance of the COVID-19 vaccine and better define possible adverse reactions involving the cochleo-vestibular system and/or immunisation anxiety-related reactions.

Accelerated Early Progression of Amyotrophic Lateral Sclerosis over the COVID-19 Pandemic.

During the COVID-19 pandemic and the related lockdowns, outpatient follow-up visits for patients with chronic neurological diseases have been suspended. Managing people affected by amyotrophic lateral sclerosis (ALS) has become highly complicated, leaving patients without the standard multidisciplinary follow-up. This study aimed to analyze the impact of the COVID-19 lockdown on ALS disease progression. We compared the clinical data and progression in the first year following diagnosis for patients who received ALS diagnosis during 2020 (G20, N = 34), comparing it with a group of diagnosed in 2018 (G18, N = 31). Both groups received a comparable multidisciplinary model of care in our Tertiary Expert ALS Centre, Novara, Italy. The monthly rate of ALSFRS-R decline during the lockdown was significantly increased in G20 compared to G18 (1.52 ± 2.69 vs. 0.76 ± 0.56; p-value: 0.005). In G20, 47% required non-invasive ventilation (vs. 32% of G18). Similarly, in G20, 35% of patients died vs. 19% of patients in G18 (p-value: 0.01). All results were corrected for gender, age, site of onset, and diagnostic delay. Several factors can be implicated in making ALS more severe, with a faster progression, such as reduced medical evaluations and the possibility of therapeutic changes, social isolation, and rehabilitation therapy suspension.

Audio-vestibular disorders and pregnancy: A systematic review.

PURPOSE: During pregnancy a woman's body undergoes many physiological changes that involve all systems and organs, including sensory ones. We conducted this systematic review to highlight current evidence and treatment options in pregnant women with audio-vestibular disorders. MATERIALS AND METHODS: A search was made on the following databases: PubMed, PubMed Central, Web of Science and Scopus. This research protocol was deposited in the PROSPERO Database. RESULTS: After application of inclusion-exclusion criteria, 30 manuscripts were included in the review. Many authors (14/15) found a slight alteration of audiometric tests during pregnancy, with a reported recovery postpartum in most of the studies (5/7). Regarding sudden sensorineural hearing loss (SSNHL), we found four articles for a total of 69 patients: the treatment of choice was intravenous Dextran 40 and intra-tympanic corticosteroids. Most included studies (4/6) found neither clinical nor epidemiological associations between otosclerosis and pregnancy in large-based sample studies. Few investigations regarded Eustachian tube function and vertigo. CONCLUSIONS: According to our results, many variations of hearing acuity during pregnancy are slight and transient and require only clinical observation. In large samples, otosclerosis appeared not to be associated with pregnancy. Clinicians should consider intra-tympanic steroids in managing SSNHL during pregnancy. Further more accurate research is needed to deepen and clarify the association between pregnancy and audio-vestibular disorders.

Health-related quality of life in patients with advanced colorectal cancer: a predictive nomogram including BMI, sex and age.

BACKGROUND: Health-related quality of life (HRQoL) is not universally assessed in metastatic colorectal cancer (mCRC) patients. We tried to identify patient subgroups for whom HRQoL assessment should be strongly encouraged. METHODS: Consecutive mCRC patients who had been deemed candidates for first-line chemotherapy were enrolled in a prospective study (NCT03873064) and asked to complete the HRQoL questionnaire EORTC QLQ-C30. Primary endpoint was the Global Health Status (GHS) of EORTC QLQ-C30. A nomogram was built for prediction of low GHS (i.e., <67%). RESULTS: Among recruited patients (n=173), a univariable logistic regression analysis (LRA) found that body mass index (BMI <23), age (>65 years) and sex (female) were significantly associated with low GHS. The multivariable LRA confirmed they were independently associated with the outcome (P values of 0.04-0.004). BMI, age and sex were included in a final predictive model (C-statistics, 67%; P=0.001) and used to build a nomogram. A total nomogram score ≥72 was associated with a risk of 28% or higher of having a low GHS. The 28% risk cut-off had a sensitivity of 90% and a specificity of 34% for identifying low GHS. A decision curve analysis revealed that a risk threshold of 28% of the model was associated to an added net benefit of ≥4% when using the nomogram. Low GHS was recorded in 58% vs. 23% of patients with >28% vs. <28% risk according to the nomogram, respectively (odds ratio 3.54, P=0.0004). CONCLUSIONS: High BMI together with young age and male sex were protective against HRQoL deterioration. In centers where HRQoL is not routinely assessed, such an assessment should be at least made for mCRC patients at risk according to the proposed nomogram (i.e., over 65-year-old females with BMI <23).

Idiopathic Sudden Sensorineural Hearing Loss in Children: A Systematic Review and Meta-analysis.

OBJECTIVE: Idiopathic sudden sensorineural hearing loss (ISSNHL) is uncommon in children, and its treatment and outcome are debated. We aimed to critically review evidence in the literature about treatment options and functional outcomes of pediatric ISSNHL. Additionally, we performed a meta-analysis of the results of combined systemic-intratympanic steroid therapy versus solely systemic treatment. DATA SOURCES: A search was run in the PubMed, Scopus, and Google Scholar databases. REVIEW METHODS: Included articles were original ISSNHL case series, written in English, with a population age ranging from 2 to 19 years. Other study types (single case reports, editorials, and reviews) and case series with known etiology of sudden hearing loss were excluded. Descriptive data of patients, treatments, outcomes, and possible prognostic factors were extracted and recorded for every included study. RESULTS: Twelve articles (7 cohort and 5 case-control studies) met all the selection criteria. Based on only the studies that provided sufficient data about clinical outcome, the pooled overall recovery rate was 67.91% (95% CI, 58.34%-77.48%). No studies showed a significant difference between systemic steroid and combined systemic-intratympanic steroid. The pooled odds ratio for combined systemic-intratympanic steroid versus systemic steroid alone was 0.90 (95% CI, 0.36-2.27) based on a random effects model, ruling out any significant difference between these treatment options. CONCLUSIONS: The results of our meta-analysis did not support combination therapy more than systemic steroid alone. Further prospective clinical trials are necessary to establish evidence-based therapies.

Long-term atrial arrhythmias incidence after heart transplantation.

OBJECTIVES: Atrial arrhythmias after heart transplantation have rarely been investigated. The aim of this study is to assess incidence, type and predictors of atrial arrhythmias during a long-term follow-up in a large population of heart-transplanted patients. METHODS: Consecutive patients undergone to heart transplantation at our Centre from 1990 to 2017 were enrolled. All documented atrial arrhythmias were systematically reviewed during a long-term follow-up after heart transplantation. Atrial fibrillation (AF), atrial flutter and tachycardias were defined according to current guidelines. RESULTS: Overall, 364 patients were included and followed for 120 ± 70 months. During the follow-up period 108 (29.7%) patients died and 3 (0.8%) underwent re-transplantation. Sinus rhythm was present in 355 (97.5%) patients. Nine patients had persistent atrial arrhythmias: 8 (2.2%) presented atypical flutter and one (0.3%) patient AF. Paroxysmal sustained arrhythmias were detected in 42 (11.5%) patients, always atrial flutters. At univariate analysis several echocardiographic (left ventricular end-diastolic diameter, TEI index, mitral and tricuspid regurgitation grade) hemodynamic (systolic and diastolic pulmonary pressure, capillary wedge pressure) and clinical (dyslipidaemia, weight, pacemaker implantation) parameters related to higher incidence of atrial arrhythmias. CONCLUSION: Persistent atrial arrhythmias, and most of all AF, are rare among heart transplantation carriers, despite substantial comorbidities resulting in significant mortality. It can be speculated that the lesion set provided by the surgical technique, a complete and transmural electrical isolation of the posterior left atrium wall, represents an effective lesion set to prevent persistent AF.

Intercalation compounds of a smectite clay with an ammonium salt biocide and their possible use for conservation of cultural heritage.

Ordered intercalation compounds between a smectite mineral clay (montmorillonite, Mt) and the ammonium salt mainly used for stone material disinfection procedures (i.e. N-Alkyl-N-benzyl-N,N-dimethylammonium chloride, shortly known as benzalkonium chloride, BAC), leading to an increase of interlayer distance from 1.3 nm up to 3.4 nm, have been prepared. The used clay/ammonium salt ratios are close to (or higher than) those often used for stone materials disinfection procedures for the conservation in cultural heritage. The prepared intercalated compounds have been studied as for their possible cation release in suitable aqueous media. Mt/BAC intercalate compounds are able to release only a fraction (if any) of the intercalated cations, eventually leading to a stable intermediate intercalate structure with interlayer distance not far from 1.9 nm, with a Mt/BAC ratio roughly equal to 4/1. The overall results indicate that Mt/BAC intercalates are possibly suitable for biocide applications in stone conservation procedures requiring both fast antimicrobial release and long-term biostatic effect.

The roman thermal complex from Curinga (Calabria - Italy).

Since ancient times, the Calabrian territories were affected continuously and in different dominations: first Magna Greece civilisation and after the Roman domination. The latter influenced strongly some areas of the Calabrian territory, where we witnessed a gradual replacement of small farmer properties with plants of the first Roman villas. An example of Roman thermal plant was in the city of Curinga (CZ), where in 1966 were found the remains of a thermal building dating to late-Roman period, probably a part of a much more complex structure identifiable as a large Roman villa. In this context are exposed the results of a first scientific aim to study the thermal complex of Curinga, with the development of a specific diagnosis protocol and its next application to the artefact itself, to get a general but exhaustive survey of its conditions, its conservation and degradation state, essential for the execution of future maintenance projects.

Insight on cellular and humoral components of innate immunity in Squilla mantis (Crustacea, Stomatopoda).

For deeper insights into the function of crustacean haemocytes in immune responses, we studied the morphology and enzyme content of circulating cells of the mantis shrimp Squilla mantis from the North Adriatic Sea, together with their ability to phagocytose foreign cells. We also assayed the enzyme content and the agglutinating and haemolytic activities of cell-free haemolymph. Three haemocyte types, i.e., hyalinocytes, semigranulocytes and granulocytes, can be distinguished, according to cell and nuclear morphology and the presence of cytoplasmic granules. All of them share the same patterns of enzyme activities and are recognised by the same lectins. Spreading cells (hyalinocytes and semigranulocytes) can ingest foreign cells; granules of semigranular and granular cells have similar cytochemical properties. Injection of Micrococcus luteus into the heart sinus results in an increase in the frequency of hyaline cells and a decrease in the frequency of granulocytes. After 24 h from the injection, a decrease in the number of phagocytosing hyalinocytes, and a general decrease in the frequency of acid phosphatase-positive cells was reported. Our data match previous results and suggest the existence of a single differentiation pathway for Squilla haemocytes with the three haemocyte morphs as different stages of cell differentiation. Results also indicate that Squilla haemolymph performs immunosurveillance, through rapid changes in haemocyte distribution, increase of antimicrobial and antioxidant enzymes and secretion of lectins stimulating agglutination, phagocytosis and encapsulation.

Effects of temperature on cellular and biochemical parameters in the crab Carcinus aestuarii (Crustacea, Decapoda).

The effects of temperature on cellular and biochemical parameters of the crab Carcinus aestuarii were evaluated. Crabs were kept for 7 days at 4, 17 (reference value) and 30 °C (salinity of 35 psu), and total haemocyte count (THC), haemocyte volume, haemocyte proliferation, phenoloxidase (PO) activity in both haemocyte lysate (HL) and cell-free haemolymph (CFH), CFH total protein and glucose levels, superoxide dismutase (SOD) and catalase (CAT) activities in both gills and digestive gland were evaluated. The lowest and the highest temperature significantly decreased THC, whereas haemocyte volume and haemolymph glucose concentration did not differ significantly among experimental conditions. Haemolymph protein concentration significantly reduced in crabs maintained at 30 °C, when compared with that of animals kept at 4 and 17 °C. Haemocyte proliferation increased significantly in crabs kept at 4 and 30 °C, when compared with that of crabs held at 17 °C. Likewise, a significantly higher PO activity was recorded in CFH from crabs kept at 4 and 30 °C, than in control crabs. Conversely, PO activity did not vary significantly in HL. With regard to antioxidant enzyme activities, a significant decrease in CAT activity was observed in gills from crabs kept at 4 °C, when compared to that of crabs kept at 17 °C and 30 °C. Results obtained demonstrated that the highest and lowest temperature tested influenced crab biological responses, and indicated that C. aestuarii modulated its cellular and biochemical parameters (mainly haemocyte proliferation, CFH protein concentrations and CFH PO activity) in order to cope with temperature.

Can starvation influence cellular and biochemical parameters in the crab Carcinus aestuarii?

Crustacea experience periods of starvation during moulting or when limited food availability occurs. The effects of starvation on Crustacea physiological responses have been demonstrated, whereas the effects of starvation on Crustacea immune parameters remain to be more fully studied. In the present study the effects of starvation on immune parameters and antioxidant enzyme activities of the crab Carcinus aestuarii were evaluated for the first time. Treated crabs were starved for 7 days, whereas control crabs were fed daily with mussels. Total haemocyte count (THC), haemocyte diameter and volume, haemocyte proliferation, cell-free haemolymph (CFH) glucose and total protein levels, and phenoloxidase (PO) activity in both haemocyte lysate (HL) and CFH were measured in crabs. In addition, superoxide dismutase (SOD) and catalase (CAT) activities were evaluated in both gills and digestive gland from crabs, in order to evaluate whether starvation induced oxidative stress in C. aestuarii. THC increased significantly in starved crabs, with respect to controls, whereas no significant variations were observed in haemocyte diameter, volume and proliferation. In CFH of starved animals glucose concentration significantly increased, whereas total protein concentration significantly reduced. A significantly higher PO activity was recorded in HL from starved crabs, than in control crabs. Conversely, PO activity did not vary significantly in CFH. Starvation did not cause significant alterations in antioxidant enzyme activities in both gills and digestive gland. Results obtained demonstrated that starvation influenced crab immune parameters, but did not induce oxidative stress. Results also indicated that C. aestuarii can modulate its cellular and biochemical parameters in order to cope with starvation.

Potential therapeutic effects of vitamin e and C on placental oxidative stress induced by nicotine: an in vitro evidence.

There have been a few studies that examined the oxidative stress effects of nicotine during pregnancy and lactation. The adverse effect of prenatal smoking exposure on human fetal development and growth has been a major public health issue. Active or passive smoking during pregnancy can result in a wide variety of adverse outcomes, including intrauterine growth retardation (IUGR), prematurity, stillbirth, and the sudden infant death syndrome. Smoking in pregnancy has also been associated with an increased risk of attention deficit and learning problems in childhood. Some studies argued that as a principal component of tobacco smoke, nicotine alone is responsible for the majority of negative reproductive outcomes. Nicotine and its major metabolite cotinine can cross the placental barrier. The level of nicotine in fetal tissues was found to be equal to or greater than the plasma nicotine level in the mothers. The oxidative stress induce by nicotine has been increasingly postulated as a major contributor to endothelial dysfunction. A large body of research has investigated the potential role of antioxidant nutrients in the prevention of endothelial dysfunction in women. Therefore, the present study was undertaken to assess the potential benefit of antioxidant supplementation on markers of placental oxidative stress in an in vitro model of endothelial dysfunction induced by nicotine, since it was previously found that nicotine is able to trigger the placental secretion of stress molecules. In this regard, we evaluated the effects of vitamin C, vitamin E and N-acetylcysteine (NAC), alone or in combination, in placental villi culture after exposure to nicotine. The effect of antioxidant nutrients on trophoblast cells proliferation and vitality was also evaluated. The results obtained suggest that in a patho-physiological condition, such as endothelial dysfunction induced by nicotine, the deleterious effect of reactive oxygen species may be counteracted by an antioxidant therapy, and there is the need to investigate the optimum dosing and timing of antioxidants administration, since an inappropriate antioxidant treatment in pregnant women may have deleterious consequences, reducing placental cells proliferation until to cell death.

Can high-dose fotemustine reverse MGMT resistance in glioblastoma multiforme?

Glioblastoma multiforme (GBM), the highest grade malignant glioma, is associated with a grim prognosis-median overall survival is in the range 12-15 months, despite optimum treatment. Surgery to the maximum possible extent, external beam radiotherapy, and systemic temozolomide chemotherapy are current standard treatments for newly diagnosed GBM, with intracerebral delivery of carmustine wafers (Gliadel). Unfortunately, the effectiveness of chemotherapy can be hampered by the DNA repair enzyme O6-methylguanine methyltransferase (MGMT), which confers resistance both to temozolomide and nitrosoureas, for example fotemustine and carmustine. MGMT activity can be measured by PCR and immunohistochemistry, with the former being the current validated technique. High-dose chemotherapy can deplete MGMT levels in GBM cells and has proved feasible in various trials on temozolomide, in both newly diagnosed and recurrent GBM. We here report the unique case of a GBM patient, with high MGMT expression by immunohistochemistry, who underwent an experimental, high-dose fotemustine schedule after surgery and radiotherapy. Although treatment caused two episodes of grade 3-4 thrombocytopenia, a complete response and survival of more than three years were achieved, with a 30% increase in dose intensity compared with the standard fotemustine schedule.

Ten-year adjuvant treatment with somatostatin analogs in a patient with atypical carcinoid of the lung.

Both typical carcinoid and atypical carcinoid (AC) of the lung are surgically curable, but AC carries a considerably worse prognosis because of a relatively high rate of recurrence. Adjuvant therapy can be conducted with radiotherapy, chemotherapy, and somatostatin analogs (SST-As), but its effectiveness in preventing locoregional and distant recurrences is yet to be fully investigated. A 48-year-old woman, presenting with AC, was free of both radiographical and biochemical signs of residual disease, after surgery and chemotherapy. To prevent disease recurrence, she underwent long-term adjuvant treatment based on SST-As. During the 10-year follow-up period, no side effects referable to SST-As have been reported and no evidence of recurrence of the disease has been detected. In consideration of the relatively high recurrence rate of the disease and of excellent tolerance for SST-As, long-term adjuvant treatment based on SST-As could become a therapeutic option for surgically cured patients with AC. Clinical investigations, conducted in large samples of patients, are necessary to evaluate the effectiveness of such an approach.