Gender oncology: recommendations and consensus of the Italian Association of Medical Oncology (AIOM).

BACKGROUND: Following the development of gender medicine in the past 20 years, more recently in the field of oncology an increasing amount of evidence suggests gender differences in the epidemiology of cancers, as well as in the response and toxicity associated with therapies. In a gender approach, critical issues related to sexual and gender minority (SGM) populations must also be considered. MATERIALS AND METHODS: A working group of opinion leaders approved by the Italian Association of Medical Oncology (AIOM) has been set up with the aim of drafting a shared document on gender oncology. Through the 'consensus conference' method of the RAND/University of California Los Angeles (UCLA) variant, the members of the group evaluated statements partly from the scientific literature and partly produced by the experts themselves [good practice points (GPPs)], on the following topics: (i) Healthcare organisation, (ii) Therapy, (iii) Host factors, (iv) Cancer biology, and (v) Communication and social interventions. Finally, in support of each specific topic, they considered it appropriate to present some successful case studies. RESULTS: A total of 42 articles met the inclusion criteria, from which 50 recommendations were extracted. Panel participants were given the opportunity to propose additional evidence from studies not included in the research results, from which 32 statements were extracted, and to make recommendations not derived from literature such as GPPs, four of which have been developed. After an evaluation of relevance by the panel, it was found that 81 recommendations scored >7, while 3 scored between 4 and 6.9, and 2 scored below 4. CONCLUSIONS: This consensus and the document compiled thereafter represent an attempt to evaluate the available scientific evidence on the theme of gender oncology and to suggest standard criteria both for scientific research and for the care of patients in clinical practice that should take gender into account.

A questionnaire to collect unintended effects of transcranial magnetic stimulation: A consensus based approach.

Transcranial magnetic stimulation (TMS) has been widely used in both clinical and research practice. However, TMS might induce unintended sensations and undesired effects as well as serious adverse effects. To date, no shared forms are available to report such unintended effects. This study aimed at developing a questionnaire enabling reporting of TMS unintended effects. A Delphi procedure was applied which allowed consensus among TMS experts. A steering committee nominated a number of experts to be involved in the Delphi procedure. Three rounds were conducted before reaching a consensus. Afterwards, the questionnaire was publicized on the International Federation of Clinical Neurophysiology website to collect further suggestions by the wider scientific community. A last Delphi round was then conducted to obtain consensus on the suggestions collected during the publicization and integrate them in the questionnaire. The procedure resulted in a questionnaire, that is the TMSens_Q, applicable in clinical and research settings. Routine use of the structured TMS questionnaire and standard reporting of unintended TMS effects will help to monitor the safety of TMS, particularly when applying new protocols. It will also improve the quality of data collection as well as the interpretation of experimental findings.

Functional Role of Cerebellar Gamma Frequency in Motor Sequences Learning: a tACS Study.

Although the role of the cerebellum in motor sequences learning is widely established, the specific function of its gamma oscillatory activity still remains unclear. In the present study, gamma (50 Hz)-or delta (1 Hz)-transcranial alternating current stimulation (tACS) was applied to the right cerebellar cortex while participants performed an implicit serial reaction time task (SRTT) with their right hand. The task required the execution of motor sequences simultaneously with the presentation of a series of visual stimuli. The same sequence was repeated across multiple task blocks (from blocks 2 to 5 and from blocks 7 to 8), whereas in other blocks, new/pseudorandom sequences were reproduced (blocks 1 and 6). Task performance was examined before and during tACS. To test possible after-effects of cerebellar tACS on the contralateral primary motor cortex (M1), corticospinal excitability was assessed by examining the amplitude of motor potentials (MEP) evoked by single-pulse transcranial magnetic stimulation (TMS). Compared with delta stimulation, gamma-tACS applied during the SRTT impaired participants' performance in blocks where the same motor sequence was repeated but not in blocks where the new pseudorandom sequences were presented. Noteworthy, the later assessed corticospinal excitability was not affected. These results suggest that cerebellar gamma oscillations mediate the implicit acquisition of motor sequences but do not affect task execution itself. Overall, this study provides evidence of a specific role of cerebellar gamma oscillatory activity in implicit motor learning.

Efficacy of topical imiquimod 3.75% in the treatment of actinic keratosis of the scalp in immunosuppressed patients: our case series.

Background: Actinic keratoses (AK) represent common cutaneous lesions, appearing in 'Field cancerization areas' and potentially evolving toward invasive neoplasm. Immunosuppressed patients frequently develop numerous and aggressive AKs.Aim: In this observational study, we report our experience with topical Imiquimod 3.75% as 'Field-directed therapy' in a cohort of immunosuppressed patients.Methods: A group of 13 immunosuppressed patients presenting multiple AKs of the balding scalp was treated with topical Imiquimod 3.75%. Each patient underwent clinical examination at fixed timepoints during the treatment (T0, T14, T28, T42) and eight weeks after the end.Results: In our cohort, the treatment was well tolerated, with minimal local adverse events. We observed a good clinical response, in terms of Lmax lesions (maximum lesion count during the course of therapy) and of AK clearance. In our group, 46% of patients showed no detectable lesions at the end of the observation period, and this result was maintained up to 1 year after the end of treatment.Conclusion: Topical Imiquimod 3.75% represents an effective and safe treatment for multiple AK of the scalp also in immunosuppressed patients. To the best of our knowledge, this is the first report on the use of this drug in this category of subjects.

Effects of low-gamma tACS on primary motor cortex in implicit motor learning.

In the primary motor cortex (M1), rhythmic activity in the gamma frequency band has been found during movement planning, onset and execution. Although the role of high-gamma oscillatory activity in M1 is well established, the contribution of low-gamma activity is still unexplored. In this study, transcranial alternating current stimulation (tACS) was used with the aim to specifically modulate low-gamma frequency band in M1, during an implicit motor learning task. A 40 Hz-tACS was applied over the left M1 while participants performed a serial reaction time task (SRTT) using their right hand. The task required the repetitive execution of sequential movements in response to sequences of visual stimuli. Sequential blocks were interleaved by a random block, which served as interference to sequence learning. Sham and 1 Hz tACS were used as control. Task performance was examined before, during and after tACS (pre-, online- and post-phase, respectively). Furthermore, cortical reactivity of M1 was assessed in the pre- and post-tACS phases, by measuring motor-evoked potentials (MEPs) elicited by single-pulse transcranial magnetic stimulation (TMS). Compared to sham and pre-tACS, the 40 Hz stimulation applied during SRTT slowed down response times in blocks that required retrieving previously learned sequences, after performing the random block. In addition, M1 cortical reactivity was selectively inhibited following 40 Hz-tACS, as quantified by reduced MEP amplitude. These results show that low-gamma tACS delivered over M1 during motor learning enhanced susceptibility to interference generated by the random sequence (i.e., proactive interference effect). Importantly, only low-gamma stimulation produced long-lasting effects on M1 cortical reactivity.

Bacteriotherapy in children with recurrent upper respiratory tract infections.

OBJECTIVE: Children with recurrent upper-airway infections (UI) represent a social issue for their economic burden and negative impact on families. Bacteriotherapy is a new therapeutic strategy that could potentially prevent infections. The current study tested the hypothesis that recurrent UI may be prevented by bacteriotherapy. PATIENTS AND METHODS: This open study was conducted in an outpatient clinic, enrolling 80 children (40 males, mean age 5.26±2.52 years) suffering from recurrent UI. Children were treated with a nasal spray containing Streptococcus salivarius 24SMB and Streptococcus oralis 89a, 2 puffs per nostril twice a day for a week; this course was repeated for 3 months. The evaluated parameters were: number of UI and number of school and work absences; these outcomes were compared with those recorded in the past year. RESULTS: The mean number of UI significantly diminished: from 5.98 (2.30) in the past year to 2.75 (2.43) after treatment (p<0.0001). The number of school and work absences significantly diminished (from 4.50±2.81 to 2.80±3.42 and from 2.33±2.36 to 1.48±2.16 respectively; p<0.0001 for both). CONCLUSIONS: This preliminary experiment suggests that bacteriotherapy using Streptococcus salivarius 24SMB and Streptococcus oralis89a nasal spray could prevent recurrent UI in children.

" The times they aren't a-changin' " rTMS does not affect basic mechanisms of temporal discrimination: a pilot study with ERPs.

In time processing, the role of different cortical areas is still under investigation. Event-related potentials (ERPs) represent valuable indices of neural timing mechanisms in the millisecond-to-second domain. We used an interference approach by repetitive TMS (rTMS) on ERPs and behavioral performance to investigate the role of different cortical areas in processing basic temporal information. Ten healthy volunteers were requested to decide whether time intervals between two tones (S1-S2, probe interval) were shorter (800ms), equal to, or longer (1200ms) than a previously listened 1000-ms interval (target interval) and press different buttons accordingly. This task was performed at the baseline and immediately after a 15-min-long train of 1-Hz rTMS delivered over the supplementary motor area, right posterior parietal cortex, right superior temporal gyrus, or an occipital control area. Task accuracy, reaction time, and ERPs during (contingent negative variation, CNV) and after the presentation of probe intervals were analyzed. At the baseline, CNV amplitude was modulated by the duration of the probe interval. RTMS had no significant effect on behavioral or ERP measures. These preliminary data suggest that stimulated cortical areas are less crucially involved than other brain regions (e.g. subcortical structures) in the explicit discrimination of auditory time intervals in the range of hundreds of milliseconds.

Adeno-tonsillar surgery in Italy.

Indications to surgery for adeno-tonsillar inflammatory disorders and analysis of the effectiveness of surgical treatment, compared with watchful waiting strategy, continue to be the subject of scientific debate. The present investigation focuses on the surgical activity of 14 Italian Otorhinolaryngological Units between 1999 and 2004. Surgical interventions (adeno-tonsillectomy, adenoidectomy, tonsillectomy) on 26915 children (age range: 2-11 years) were considered. Data on adeno-tonsillar interventions were analysed in relation to other interventions of ENT interest, performed in the same units and in the same period. Adeno-tonsillar interventions accounted for 35.4% of all operations of ENT interest. Adeno-tonsillectomy accounted for 56.6% of overall adeno-tonsillar operations, adenoidectomy 31.6%, tonsillectomy 11.8%. The percentage for the three interventions was homogeneous in the period of the study and in the recruited units. The percentage of children who underwent adeno-tonsillar surgery in paediatric units was higher as compared to general units, as far as concerns the overall number of operations performed. In southern Italy, the number of adeno-tonsillar interventions, in general, and of adeno-tonsillectomy, in particular, was higher compared to that in northern Italy. Results of the present study suggest that environmental factors, cultural issues and local health demands, may influence indications and, therefore, the different incidence of the operations under consideration in the units taking part in the investigation.

Safety of electronic molecular resonance adenoidectomy.

Adenoidectomy is one of the most frequent operations in children. In order to reduce hospital stay costs, today, this procedure is performed as day surgery. Even though adenoidectomy is not considered risky, some minor complications may occur, the most important being bleeding (0.5-8% incidence). The surgical technique used can influence considerably postoperative pain and time to recovery. This aspect is essential in the management of day surgery patients, for whom the need of safe and rapid maneuvers associated with early recovery determines the choice of the surgical procedure. Recently, we developed a surgical technique based on the use of an electronic molecular resonance tool associated with bendable suction electrocautery. This study was carried out on 600 patients, divided into two groups, the first undergoing ablation using the molecular resonance tool and the second undergoing curette adenoidectomy. The two groups were homogeneous for age, sex, surgical indications, and grade of adenoid hypertrophy. The following parameters were considered: duration of surgery, importance of intraoperative bleeding, time to cicatrization, incidence of bleeding complications. Duration of surgery and intra- and postoperative bleeding were much lower in the first group than in the group undergoing traditional adenoidectomy. In addition, rhinopharyngeal complete cicatrization, defined as absolute absence of pseudomembrane, was much quicker in the first group, as assessed by postoperative endoscopy. Another major advantage offered by the molecular resonance tool is the accuracy of surgery performed under visual control in a practically bloodless field. To sum up, this method, thanks to its technical features and safety, is particularly indicated in children and in patients with coagulation disorders.

Acute mastoiditis: a 10 year retrospective study.

This retrospective study reviews our experience in the management of acute otomastoiditis over 10 years. During the study period we identified 40 cases in children aged 3 months-15 years with a peak incidence in the second year of life. Sixty per cent of them had a history of acute otitis media (AOM). All the children were already receiving oral antibiotic therapy. Otalgia, fever, poor feeding and vomiting were the most common symptoms, all the children had evidence of retroauricolar inflammation. Computerized tomography (CT) and magnetic resonance imaging (MRI) were used to support the diagnosis and to evaluate possible complications. Streptococcus pneumoniae was the most common isolated bacterium. All the patients received intravenous antibiotics, 65% of children received only medical treatment, 35% also underwent surgical intervention. Mean length of hospital stay was 12.3 days. Cholesteathoma was diagnosed in one child. We conclude from our study that acute otomastoiditis is a disease mainly affecting young children, that develops from AOM resistant to oral antibiotics. Adequate initial management always requires intravenous antibiotics, conservative surgical treatment with miryngotomy is appropriate in children not responding within 48 h from beginning of therapy. Mastoidectomy should be performed in all the patients with acute coalescent mastoiditis or in case of evidence of intracranial complications.

Monothermal air caloric test in children.

We compared the efficacy of bithermal (BAT) and monothermal cold (MCAT) and warm (MWAT) air caloric tests in identifying labyrinthine function anomalies in the child. At first, we established confidence intervals of normality for both monothermal tests in 40 children (22 males, 18 females) aged 6-14 years, clinically healthy and normal as previously shown by BAT. Subsequently, we compared the results of BAT with those of MCAT and MWAT performed in 46 children (22 males, 24 females) aged 6-14 years, affected by multiple labyrinthine diseases. These results confirmed that, as in the adult, MCAT alone should not be used in the evaluation of labyrinthine function in vertiginous patients. As to MWAT, we obtained good sensitivity and specificity with respect to BAT (83% and 90% for 90% probability; 78% and 92.5% for 95% probability). Sensitivity values increased or decreased depending on the disease causing vertiginous symptoms, with decreased or increased number of false negatives. In our opinion, MWAT cannot replace BAT for the study of labyrinthine function in children. MWAT alone can be used when vertigo is ascribable to vestibular neuritis or to endogenous disease (dysmetabolic, dyscrasic, dysendocrine).

Nasal brushing: a clinically useful procedure in pediatric patients with rhinosinusitis?

Sinusitis is a common complication of non-allergic and allergic rhinitis, and can trigger lower respiratory diseases, such as bronchitis and asthma. Standard radiography is unable to give any data about the underlying pathological mechanisms (infectious or allergic) involved and infectious rhinosinusitis is very common in pediatric age, even in allergic patients. We investigated the possibility of obtaining more useful diagnostic information, performing nasal brushing (NB) on 117 children with recurrent respiratory symptoms. The following hypothesis were evaluated: (1) whether NB neutrophil/eosinophil percentages and/or NB culture could predict the radiological evidence of maxillary sinusitis; and (2) whether differences between nonallergic and allergic patients could be detected. In the total patient group and in the nonallergic group, the comparison of NB neutrophil percentages in patients with and without maxillary sinusitis showed a statistically significant difference (median 2 and 18%, respectively; P < 0.001). In the nonallergic group, a NB neutrophil rate > or = 5% was chosen as a cut-off between positive and negative NB diagnosis of rhinosinusitis and NB data were compared with radiological investigations. The results obtained showed that NB was fairly sensitive (91%) and predictive (84%). In allergic patients, neither neutrophil nor eosinophil percentages significantly correlated with the presence of sinusitis. Microbiological studies showed that, even if the presence of bacteria in NB resulted associated with sinusitis, a negative culture was not predictive of the absence of the disease. We therefore suggest that NB describes the present inflammatory status of the upper airways, hence, it is more suitable to describe the inflammation related to ongoing upper respiratory tract infections rather than chronic inflammation due to allergic rhinitis, characterized by relapsing episodes of acute inflammation. In conclusion, we propose to consider NB a reliable tool in the diagnosis of rhinosinusitis, particularly in nonallergic pediatric patients. Compared to standard radiological techniques, NB makes it possible to avoid radiation exposure and gives information about the pathological mechanisms involved in the single patient.

Plasma and tonsillar tissue pharmacokinetics of teicoplanin following intramuscular administration to children.

The population pharmacokinetics of teicoplanin in plasma and tonsillar tissue in children was determined following intramuscular administration. Thirty seven patients in all received either a single 5 mg/kg dose; 2 doses of 5 mg/kg, 12 h apart; 3 doses of 5 mg/kg, 12 h apart; or, a single 10 mg/kg dose. Limited data, comprising a maximum of 2 blood samples and 1 tonsillar sample were taken from each patient, with the maximum time being 48 h after the first dose of teicoplanin (in the 3 x 5 mg/kg dosing schedule). All plasma data were analyzed simultaneously by a maximum likelihood method employing a modified EM algorithm. A first-order absorption, one-compartment disposition model was fitted to the data. Mean parameter values (with lower and upper 95% confidence intervals) were: clearance/bioavailability, 0.024 L h(-1) kg(-1) (0.020-0.027); volume of distribution/bioavailability, 0.61 L kg(-1) (0.54-0.70); absorption rate constant, 0.43 h(-1) (0.31-0.61). A first-order transfer model for distribution of teicoplanin between plasma and tonsillar tissue was fitted to the tonsil data. The mean parameter values (95% confidence intervals) were: transfer rate constant between plasma and tonsils 0.49 h(-1) (0.35-0.67); transfer rate constant between tonsils and plasma 0.73 h(-1) (0.52-1.03). These rate constants correspond to a distribution half-life of 0.95 h and an equilibrium distribution concentration ratio between tonsillar tissue and plasma of 0.67. After normalising clearance and volume of distribution for body weight, there was no further influence of body weight on the pharmacokinetic parameters. Also, there was no effect of dose, and as two formulations were used, one for the 5 mg/kg dose and the other for the 10 mg/kg dose, no effect of formulation on the pharmacokinetics of teicoplanin after im (intramuscular) administration was found.

Electronystagmography findings in child unilateral sensorineural hearing loss of probable viral origin.

We studied the labyrinthine function in a group of 72 children aged between 4 and 14 years affected by unilateral sensorineural hearing loss of probable viral origin. From the analysis of the results obtained we confirm the concomitance of cochlear and vestibular damage. However, there were no statistically significant differences between type of audiogram at onset of hearing loss and type of electronystagmography (ENG), while we found a direct correlation between the presence of vertigo or dizziness and type of ENG. Finally hearing recovery was influenced by the presence of vertigo or labyrinthine function alterations. The results of statistical analysis confirmed a significant statistical difference between patients with vertigo or dizziness (V(+)) and those without vertigo (V(-)) and also between patients with ENG 3 (subjects with spontaneous nystagmus or positional nystagmus and canal paresis ipsilateral to the cochlear lesion) and those with ENG 1 (subjects without spontaneous nystagmus or positional nystagmus and with normal vestibular reflex). In fact, hearing recovery was worse in V(+) group and in ENG 3 group.

Otoneurologic evaluation of child vertigo.

In this study 282 children with vertigo are subdivided (according to previous experiences) into three large groups: (1) vertigo and cochlear diseases; (2) vertigo as an isolated symptom; and (3) vertigo and C.S.N. diseases. Due to the difficult etiopathogenetic investigation of the patients from the second group, the authors focused on that group as they are less studied, are without associated symptoms (deafness--first group; CNS diseases--second group) and where vertigo appears as an idiopathic and an isolated symptom. A careful anamnestic, clinical and instrumental analysis leads to the following observations: (1) in decreasing order of frequency we find the third group, followed by the first and finally by the second; (2) in spite of the overall lower incidence of the second group, this latter includes the paroxismal benign vertigo (PBV) which is overall the second most frequent vertiginous form (after vertigo due to cranial trauma). In this group the authors underline the reasonably high incidence of the iatrogenic syndromes, insisting on the need of their accurate prevention of these risks; (3) the authors confirm that, nowadays, a reliable etiopathogenetic cause of the apparently isolated vertigo (except for the ascertained iatrogenic forms) cannot be identified. Moreover, in spite of its frequency, PBV is the less known form of vertigo, of which we cannot give a certain diagnosis and which can be identified only the the exclusion of all the other known forms through instrumental and clinical observations.

[Chronic sinusitis in children. Current role of diagnostic imaging]. / La sinusite cronica del bambino. Ruolo attuale della diagnostica per immagini.

A retrospective study of a large series of patients (5,100 cases of radiologically confirmed rhino-sinusitis) was carried out to assess the efficacy of traditional radiology in the diagnosis of chronic sinusitis and the specific role of more recent imaging techniques. Traditional radiography, often limited to the naso-occipital projection (lack of collaboration), allows a reliable examination only of maxillary sinus. "Typical" findings of chronic sinusitis have been identified as "polipoid" thickening of the mucous membrane and localised parietal opacity. Both maxillary sinuses are involved in approximately 91% of cases, with ethmoidal involvement in 53%. Thickened mucosal walls and retention cysts may be obscured by inflammatory exudate: the air space is reduced and the sinus appears cloudy or opaque (acute reinflammation). The overall frequency of chronic sinusitis is 11.1% (67% in the 8-14 age range, 29% in the 5-8 age range and 4% in the 2-5 age range). Complications are rare (4 cases). Whereas echotomography provides limited and inconstant findings, CT and MRI are indicated in case of isolated opacity of a maxillary sinus, persistent after treatment: the former allows a detailed study of the bone, the latter enables to obtain a better tissue characterization. MRI often allows the differential diagnosis between inflammatory diseases and malignant tumors.

[Reduction of intra- and post-operative bleeding after treatment with a peptide fraction derived from bovine factor VIII]. / Diminuzione del sanguinamento intra e post-operatorio dopo trattamento con una frazione peptidica derivata dal fattore VIII bovino.

The most common post-operative complication of adenotonsillectomy is an excessive bleeding. This problem persists although the laboratory investigations may exclude hemocoagulative anomalies and the anamnesis is able to show the presence or not of genetic factors or constitutional disease. Even if the surgical operation is performed in a technical proper way, the risk of bleeding is still present. Therefore we have valued new prospects of application in pediatric O.R.L. of a peptide fraction from bovine factor VIII. This compound has proved to be able to reduce the bleeding time. We valued the action of this drug compared with that of tranexamic acid and in comparison with the results obtained before treatment. Furthermore, we have also investigated the possibility of influence of this drug on haemocoagulative parameters and we have concluded that the drug does not show any effect on them.

[Therapeutic use of a peptide fraction derived from bovine factor VIII in epistaxis in children]. / Utilizzaione terapeutica di una frazione peptidica derivata dal fattore VIII bovino nelle epistassi in età pediatrica.

The results obtained in patients suffering from essential epistaxis in paediatric age using a peptide fraction derived from the enzymatic hydrolysis of bovine factor VIII (VUEFFE-Baldacci) are reported. Carbazochrome sodium sulphate was employed for comparison purposes. Vueffe is effective in reducing haemorrhagic episodes without modifying the laboratory parameters investigated.

[The influence of click polarity and stimulation rate on the auditory evoked response in relation to age]. / Influenza della polarità dei clicks e della frequenza di stimolazione sulle risposte acustiche evocate (ABR) in rapporto all'età.

In order to study the changes which occur in phase of the click stimulus and its relation to the stimulus repetition rate on the auditory brainstem response (ABR) as a function of age, the Authors recorded the ABR from the scalp's surface of 10 newborns and 40 infants, 3 months, 6 months, 1 year and 3 years old as well as from 10 normal adults. The stimulus was a square wave of 0.1 msec duration and 90 dBHL level. The stimulus equipment was calibrated twice under visual inspection to ensure that the C and R clicks resulted in an initial membrane deflection toward and from the ear drum respectively. No significant differences could be found for the latencies and amplitude in the C-R comparison. However, the mean values of the complete group of test subjects showed most intraindividual stability for the conventional click stimulation. The latency of the ABR with excitation of the cochlea seemed to be mainly determined by the internal oscillation sequence in the cochlea and not by the stimulus polarity. The amplitudes and latencies of the ABR components tend to decrease when the stimulus rate increases and the age decreases. The importance of the stimulus characteristics is discussed and some suggestions for clinical use of ABR are made.