Biomedical subjects

Michele Ferrara

Publications and source records attributed to Michele Ferrara.

15 recordsLinked to original sources

PubMed2026

Hyperprogression Upon Cemiplimab Alone or With Short Course Chemotherapy in PD-L1 ≥ 50% Non-small Cell Lung Cancer: A Biomarker Guided Multicenter International Phase 2 Trial-HYPERBOLIC Study.

BACKGROUND: Immune checkpoint inhibitor (ICI) monotherapy is the standard first-line treatment for advanced non-small cell lung cancer (NSCLC) with PD-L1 ≥ 50%; however, up to 30% of patients experience early progression or death, including cases of hyperprogressive disease (HPD). High baseline levels (≥ 30.5%) of circulating CD10- low-density neutrophils (LDNs) have been associated with increased HPD occurrence. Emerging evidence suggests that combining ICI with platinum-based chemotherapy (PCT) may mitigate the risk of HPD. Currently, no prospective studies have addressed HPD prevention in this context. PATIENTS AND METHODS: HYPERBOLIC (NCT07274384) is a phase 2, randomized, open-label, multicenter, international trial evaluating whether adding 3 cycles of PCT to first-line cemiplimab reduces HPD rate in stage IV NSCLC with PD-L1 ≥ 50% and CD10- LDNs (identified by flow cytometry as CD15⁺CD11b⁺ within the PBMC fraction, with immature cells defined by loss of CD10) ≥ 30.5%. Seventy-four patients will be randomized (1:1 ratio) to receive cemiplimab alone or cemiplimab plus 3 PCT cycles, followed by cemiplimab maintenance. Randomization will be stratified by Lung Immune Prognostic Index. The first computed tomography scan at week 7 after treatment start will assess HPD occurrence, defined as RECIST v 1.1. disease progression with a delta tumor growth rate (ΔTGR) ≥ 50% and/or TGR ratio ≥ 2. The primary endpoint will be the combined rate of HPD and early death (death within 12 weeks with no radiological evaluation). Secondary endpoints will be HPD rate according to alternative definitions, overall survival, progression free survival, objective response rate, and safety. An extensive translational research platform will include spatial transcriptomics of tumor tissue, single-cell RNA sequencing of PBMCs, circulating-free DNA and plasma factors profiling, and saliva/stool microbiome genomics and metabolomics, to longitudinally explore tumor-host dynamic interactions during treatment. CONCLUSION: to our knowledge, HYPERBOLIC is the first prospective, biomarker-driven trial investigating early treatment escalation based on HPD risk in PD-L1-high NSCLC.

CD10↗

PubMed2004

Callosal effects of transcranial magnetic stimulation (TMS): the influence of gender and stimulus parameters.

Transcranial magnetic stimulation (TMS) of the motor cortex of one hemisphere (conditioning stimulus, CS) inhibits EMG responses evoked in distal hand muscles by a magnetic stimulus given at appropriate interval later over the opposite hemisphere (test stimulus, TS). The common interpretation attributes this effect to an inhibition produced at cortical level via a transcallosal route. The variability of cortical excitability as measured by the interhemispheric paired-pulse (PP) technique has been assessed in healthy subjects in order to compare sub- and supra-threshold intensity of CS (80% versus 120% of individual motor threshold, MT). Within- and between-subject variability relating, respectively, to interhemispheric and gender differences were also assessed. Results point to an efficacy of a magnetic CS on one hemisphere in inhibiting EMG responses of the abductor digiti minimi (ADM) stimulated by a TS delivered over the opposite hemisphere in a range of intervals centered at 12ms. These reductions were produced by the 120% suprathreshold CS, while the 80% subthreshold CS did not affect EMG responses. Females showed a higher transcallosal inhibition than males, suggesting gender differences in interhemispheric connectivity that concern the anterior half of the trunk of the corpus callosum.

Adult↗

PubMed2003

Psychosocial factors discriminate oligozoospermic from normozoospermic men.

OBJECTIVE: To compare the profile of psychosocial variables in a group of oligozoospermic and normozoospermic men for assessing the hypothesis of a relationship between impaired seminal status and psychosocial factors. DESIGN: Double-blind investigation of the psychosocial differences between oligozoospermics and normozoospermics. SETTINGS: Healthy volunteers in a clinical environment. PATIENT(S): Two hundred eighty men attending their first seminal examination. INTERVENTION(S): We selected 37 oligozoospermic patients on the basis of sperm concentration and 37 normozoospermic controls for comparison. OUTCOME MEASURE(S): Differences in alexithymia (difficulty identifying feelings, difficulty describing feelings, externally oriented thinking), personality traits (extroversion, neuroticism, psychoticism), and coping style toward stressors (task-oriented coping, emotion-oriented coping, avoidance-oriented coping) were assessed in the two groups. RESULT(S): Wilk's Lambda (.79) of the discriminant analysis showed a statistically significant difference between the two groups. The following variables met the inclusion criterion in the discriminant function: psychoticism and difficulty describing feeling. This analysis also showed a high probability of correct classification of oligozoospermic men on the basis of the psychosocial variables. CONCLUSION(S): The relationship between psychosocial variables and seminal status has been confirmed in a group of oligozoospermic and normozoospermic men.

Adaptation, Psychological↗

PubMed2003

Reproducibility of callosal effects of transcranial magnetic stimulation (TMS) with interhemispheric paired pulses.

Transcranial magnetic stimulation (TMS) of the motor cortex of one hemisphere (conditioning stimulus (CS)) inhibits EMG responses evoked in distal hand muscles by a later magnetic stimulus given at an appropriate interval, over the opposite hemisphere (test stimulus (TS)). This effect is commonly attributed to an inhibition produced at cortical level via a transcallosal route. The present study assessed the reproducibility of the transcallosal inhibition effects in different sessions in healthy subjects. Within- and between-subject variability, relating to interhemispheric differences was also evaluated. A magnetic CS on one hemisphere effectively inhibited EMG responses of the abductor digiti minimi stimulated by a TS delivered over the opposite hemisphere in a range of intervals centered at 12 ms. Even though group effects were reproduced in separate sessions, the high between- and within-subject variability yielded low test-retest correlations. This differentiation forces the definition of reproducibility (or repeatability), as the replication of the same mean curves of EMG reduction, and of reliability, as the between- or within-subject correlations between values of specific EMG measures.

Adult↗

PubMed2003

Effect of total sleep deprivation on the landmarks of stage 2 sleep.

OBJECTIVE: To assess the effects of total sleep deprivation on sleep spindle and K-complex (KC) density. METHODS: Eight healthy male subjects (mean age=23.4 years) participated in the experiment: they slept in the laboratory for 3 nights (one adaptation, one baseline, one recovery); baseline and recovery night were separated by a period of 40 h of continuous wake. RESULTS: One night of total sleep deprivation caused a doubling of slow-wave sleep (SWS) amount, an increase of sleep efficiency and a reduction of the latencies of non-rapid eye movement (NREM) sleep stages during the recovery night. These effects were accompanied by a significant reduction in spindle density in the first sleep cycle of the recovery night. Mean KC density did not change as a result of total sleep deprivation, while KC density and inter-KC intervals showed linear trends across the first 4 sleep cycles, respectively decreasing and increasing. Finally, a clear evidence of an antagonist relationship between spindle and KC changes across sleep cycles was provided. CONCLUSIONS: The present study further supports the existence of a reciprocal relationship between SWS and sleep spindles, but fails to show an increase of KC density after total sleep deprivation. The opposite time courses of spindle and KC density across sleep cycles points to an antagonist relation between the two main phasic events of NREM sleep. The latter result, together with the increase of inter-KC distance and the decrease of KC density across subsequent sleep cycles, is consistent with the hypothesis of a role of the spontaneous KC as the "forerunner" of delta waves.

Adult↗

PubMed2003

Sleep spindles: an overview.

Sleep spindles are a distinctive EEG phasic feature of NREM sleep and are prevalent during stage 2 as compared to slow wave sleep. While the neurophysiological mechanisms of spindle generation, that involves thalamic and corticothalamic networks, have been recently delineated and are briefly reviewed, their definitive functional meaning still remains to be elucidated. This review summarizes the present knowledge on visually scored and automatically detected spindles, as well as the literature on EEG power in the sigma band. Among the factors known to affect sleep spindles and sigma activity, their intra-cycle temporal dynamics, their time-course across sleep cycles, the reciprocal relationship with delta activity, the effects of sleep deprivation, of circadian factors and of ageing, and their role in information processing have been discussed. Moreover, specific attention has been paid to the existence of functionally and topographically distinct slow- and fast-spindles, also taking into account the presence of large inter-individual differences. Nevertheless, several fundamental issues remain to be elucidated: the physiological mechanisms controlling age-related changes in spindle parameters; the role of melatonin as a spindle-promoting agent; the relationships between plastic mechanisms (after stroke, or as a consequence of learning) and modifications in spindle activity; the possibility of using some spindle parameters as an index of the severity of developmental disorders in abnormal maturational processes.

Aging↗

PubMed2002

Are polysomnographic measures of sleep correlated to alexithymia? A study on laboratory-adapted sleepers.

OBJECTIVE: Since recent findings have pointed to a correlation between alexithymia and measures of poor sleep quality during the first night of adaptation to a sleep laboratory, the aim of the current study was to assess the same relation in healthy laboratory-adapted sleepers. As a further measure of rapid eye movement (REM) sleep characteristics, REM density was also measured. METHODS: Twenty-seven male subjects, without sleep or psychiatric disorders, filled out the 20-item Toronto Alexithymia Scale (TAS-20) and slept for two consecutive undisturbed nights. Polysomnography and REM density were measured in the postadaptation night. RESULTS: Alexithymia scores did not correlate significantly with any polysomnographic variable or with REM density. Only the Externally Oriented Thinking (EOT) subscale showed a negative association with REM latency. Multiple regression on selected sleep measures as predictors confirmed these results. CONCLUSION: Results do not extend to normal sleep the association previously found between alexithymia and a poor quality of sleep during the adaptation night in the sleep laboratory. The only polysomnographic measure showing an association, albeit little, with one facet of alexithymia was REM latency.

Adult↗

PubMed2002

Regional differences of the temporal EEG dynamics during the first 30 min of human sleep.

The analysis of the time-course of different EEG bands during the first sleep cycle has up to now taken into account mostly central derivations. In the present study, we assessed the topographical differences of the time-course of different EEG bands during the first 30 min of sleep, by analysing the EEG power from four different scalp locations along the antero-posterior axis. Correlation of EEG bands time courses within and between each derivation has also been evaluated. Delta-theta (1-6.75 Hz) and alpha (7-10.75 Hz) activities exhibited an antero-posterior gradient with maximal power on the frontal lead and increased at all derivations in the first 15 min and 5 min periods, respectively. Then alpha power decreased at all derivations, but the frontal. Sigma EEG power (11-15.75 Hz) showed a coherent behavior over the four derivations, characterized by a steep increase in the first 3-5 min of sleep, followed by a stable decreasing trend. Beta power (16-25.75 Hz) linearly decreased only on the more posterior derivations, abruptly increasing on the frontal lead after a 15 min interval. Correlations between delta-theta and alpha band were higher on the frontal derivation. Moreover, frontal alpha was strongly related to delta-theta activity on all the four derivations, while occipital alpha was not. The negative correlations between delta-theta and beta time courses were very high on all derivations but the frontal one. This study shows the existence of topographical differences in the time-course of different EEG bands during the first 30 min of sleep. The peculiar behavior of the alpha and beta EEG bands over the frontal derivation indicates the need to re-consider the functional role of traditional EEG bands during sleep.

Adult↗

PubMed2002

Cortical EEG topography of REM onset: the posterior dominance of middle and high frequencies.

OBJECTIVES: To investigate the brain topography of human sleep electroencephalography (EEG) along the antero-posterior axis during rapid eye movement sleep (REM) onset and REM offset, by means of a quantitative analysis of EEG changes. METHODS: EEG power values were calculated across a 1.00-25.75 Hz frequency range during time intervals preceding and following REM onset of the first 4 sleep cycles of 10 normal subjects. Topographical changes were assessed through Fpz-A1, Fz-A1, Cz-A1, Pz-A1, Oz-A1 recordings during NREM-REM-NREM transitions. RESULTS: The temporal dynamics of REM onset is characterized by a specific topographical pattern of EEG changes with a relatively higher EEG activity at posterior sites: Oz does not show any clear change within the alpha and beta frequencies, at variance with the marked reductions of the other sites, while it shows reductions of power in the delta/theta and sigma frequency ranges of smaller size as compared to the other sites. REM offset does not appear as a mirror-image of REM onset, since the pattern of regional differences characterizing the NREM sleep preceding REM onset is not fully reached. CONCLUSIONS: REM onset is characterized by a general change of EEG activity toward a relative occipital diffusion of power, specifically distinguished by a posterior dominance of middle and high frequencies.

Adult↗

PubMed2002

Topographical changes in N1-P2 amplitude upon awakening from recovery sleep after slow-wave sleep deprivation.

OBJECTIVES: To assess auditory evoked potentials (AEPs) before sleep and upon 3 awakenings during an undisturbed baseline night and to compare them to AEPs during a night characterized by a recuperative increase in the amount of slow-wave sleep (SWS) as a consequence of two consecutive nights of selective SWS deprivation. METHODS: Ten male subjects slept in the laboratory for 6 consecutive nights. The first 2 nights were undisturbed. The 3rd night was considered as baseline. During the 4th and 5th nights, selective SWS deprivation was obtained by means of acoustic stimulation. The 6th night was a recovery. The data reported here were collected during the baseline and the recovery night. Subjects were awakened 3 times: after 2 h, 5 h (nocturnal awakenings) and 7.5 h (final morning awakening) of sleep, respectively. All the awakenings were carried out from stage 2. The AEP recordings were carried out in bed, while subjects were performing a simple auditory reaction time task. RESULTS: The amplitude of the N1-P2 complex decreased upon the first awakening of the baseline night as compared to pre-sleep wakefulness levels; during the recovery night, the decrease of N1-P2 amplitude was present also upon the second and final awakening. N1 latency increased upon the two nocturnal awakenings regardless of the night, while P2 latency was not affected. Moreover, the N1-P2 amplitude increased during recovery at the frontal midline derivation as compared to baseline, while it decreased at Pz and Oz. CONCLUSIONS: The N1-P2 amplitude and, to a lesser extent, the N1 latency, are sensitive in showing a state of brain deactivation during the sleep-wake transition. The decrease of N1-P2 amplitude at the parieto-occipital locations during recovery is coherent with the hypothesis of a functional link between SWS amount and cortical hypoarousal upon awakening. The unexpected increase of the same variable at Fz can be interpreted as the effect of a compensatory effort of the frontal areas for the increased homeostatic drive for sleep during the recovery night.

Adult↗

PubMed2002

Interhemispheric asymmetry of human sleep EEG in response to selective slow-wave sleep deprivation.

Recent evidence suggests that the human sleep electroencephalogram (EEG) shows regional differences over both the sagittal and coronal planes. In the present study, in a group of 10 right-handers, the authors investigated the presence of hemispheric asymmetries in the homeostatic regulation of human sleep EEG power during and after selective slow-wave sleep (SWS) deprivation. The SWS deprivation was slightly more effective over the right hemisphere, but the left hemisphere showed a markedly larger increase of EEG power in the 1.00-24.75 Hz range during recovery-night non-REM sleep, and a larger increase of EEG power during both deprivation-night and recovery-night REM sleep. These results support the greater need for sleep recuperative processes of the left hemisphere, suggesting that local sleep regulation processes may also act during REM sleep.

Adult↗

PubMed2002

Regional differences of the human sleep electroencephalogram in response to selective slow-wave sleep deprivation.

The purpose of this study was to assess the topographic changes in sleep recuperative processes in response to selective slow-wave sleep (SWS) deprivation. SWS was suppressed on two consecutive nights by means of acoustic stimulation. The electroencephalogram (EEG) power of baseline, deprivation and recovery nights was analysed in 1 Hz bins. During the SWS deprivation nights, large decreases of EEG power were found at frontopolar, central and parietal derivations encompassing the delta, theta and alpha range, while only slow delta (0.5-2 Hz) was affected at the frontal derivation. Recovery sleep was characterized by a generalized increase of power during non-REM sleep encompassing the delta, theta and alpha bands, with a clear antero-posterior gradient. The coherent behaviour of different EEG bands with traditionally different electrophysiological meanings during non-REM sleep suggests that, in light of the recent advances in sleep neurophysiology, a re-examination of the functional role of EEG rhythms during sleep is needed. The 'resistance' to selective SWS deprivation of the frontal area, together with its larger increase of EEG power during recovery, may be interpreted as a sign of a greater sleep need of the frontal cortical areas, confirming that some aspects of the regulatory processes of human sleep are local in nature and may show use-dependent characteristics.

Adult↗

PubMed2002

The cyclic alternating pattern decreases as a consequence of total sleep deprivation and correlates with EEG arousals.

The aim of this study was to assess the sensitivity of the cyclic alternating pattern (CAP) parameters to the increased need for recuperation that follows one night of sleep deprivation. Nine normal male subjects were recorded for 3 nights [adaptation, baseline (BSL) and recovery (REC)]. BSL and REC nights were separated by a 40-hour sleep deprivation. Recovery after sleep deprivation was characterized by a decrease in stage 1, stage 2 and sleep latency, and an increase in slow wave sleep (SWS) and the sleep efficiency index, while rapid eye movement (REM) and non-REM (NREM) time did not differ as compared to BSL sleep. CAP parameters were significantly affected by sleep deprivation, and the main results were the following: (1) the CAP rate (time spent in CAP phases/NREM time) significantly decreased from 38.85 to 31.47%, and (2) within phase A subtypes, there was a significant decrease in A3 subtypes (from 38.11 to 19.57). Furthermore, the number of arousals scored according to American Sleep Disorders Association rules strongly correlated with A3 subtypes during both the BSL (r = 0.79) and REC nights (r = 0.95). These results indicate that recuperative processes after sleep deprivation are also associated with a lesser arousal instability as defined by the reduction of the CAP rate, which is strongly correlated with EEG arousals.

Adult↗

PubMed2001

How much sleep do we need?

There is increasing concern for sleeplessness-related risks in modern society. Some recent epidemiological data seem to support the view that many segments of the adult population have chronically inadequate sleep. On the other hand, some experts have claimed that our core, basic amount of sleep is around 6 h per night, and that the rest of our sleep can be easily curtailed, being unnecessary to fulfill any sleep need. However, experimental data on the effects of both acute and cumulative partial sleep deprivation (PSD) consistently point out that sleep restriction has substantial negative effects on sleepiness, motor and cognitive performance and mood, as well as on some metabolic, hormonal and immunological variables. As chronic PSD may have serious long-term adverse health effects, it should be avoided in the general population. In the short-term, the effects of sleep curtailment seem to accumulate linearly, while the effects of long-term PSD should be further investigated, as the few available studies are flawed by methodological weaknesses. On the other hand, there is evidence that extending sleep by 2-3 h beyond the norm produces only marginal benefits for an average individual. Finally, it is underlined that, as large individual differences do exist in the need for sleep, the search for the sleep need may be vain. A somnotypology, taking into account age, gender and the position in both the sleep-alert and the morningness-eveningness continuum, should help in the search for the actual individual sleep need. 2001 Harcourt Publishers Ltd

Journal Article↗

PubMedDate not supplied

Alexithymia and dream recall upon spontaneous morning awakening.

OBJECTIVE: The issue of a quantitative and qualitative impoverishment of dream activity in alexithymic subjects was assessed by analysis of the 14-day dream reports of two groups of accurately selected alexithymic and nonalexithymic subjects. METHODS: Ten alexithymic and 10 nonalexithymic women were selected from a larger sample of 160 undergraduate students. The transcriptions of their audio-recorded dream reports on 14 consecutive morning awakenings were compared with regard to their length and emotional content. Self-ratings obtained from sleep and dream diaries were further considered to assess between-groups differences in dream recall frequency and in the emotional valence, vividness, and bizarreness of dreams. RESULTS: Dream recall frequency and mean length of dream reports were lower in alexithymic than in nonalexithymic subjects. There were no significant between-groups differences in emotional valence, vividness, bizarreness, and emotions scored according to the Hall and Van de Castle coding system. CONCLUSIONS: The results suggest a general difficulty of alexithymics in accessing (recalling) their dreams.

Adult↗