Effectiveness and safety profile of mepolizumab in chronic rhinosinusitis with nasal polyps: Real life data in a tertiary care.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by a type 2 pattern of inflammation. Mepolizumab was approved for the treatment of CRSwNP in 2021, it may be useful to evaluate its safety profile in a real-world setting. AIM: This work aimed to prospectively highlight the effectiveness and safety profile of Mepolizumab in patients with CRSwNP enrolled in the Otorhinolaryngology Unit of the University Hospital of Messina. METHODS: An observational cohort study was carried out considering all patients treated with Mepolizumab. A descriptive analysis was conducted reporting all demographic characteristics, endoscopic evaluations, and symptom conditions. RESULTS: A total of 30 patients were treated with Mepolizumab, one patient discontinued the treatment. A statistically significant reduction in the Sino-Nasal Outcome Tests-22 (SNOT-22) and nasal polyp score (NPS) was shown at the 6th and 12th months compared to baseline values (SNOT-22, -33 and - 43, p < 0.001 for both comparisons; NPS, 0 and - 1, p < 0.001 for both comparisons). The median (Q1-Q3) sniffin' sticks test score increased from 7 (6-8) at the 6th month to 11 (10-13) at the 12th month. Seven patients (24.1 %) reported pain at the injection site, accompanied by redness, warmth, and tenderness within the first 24 h post-injection with a median duration of three days from the onset. CONCLUSIONS: Given the optimal treatment response and the minimal adverse effects observed, clinicians should consider Mepolizumab a safe and effective treatment in CRSwNP patients. Further studies in real-life setting are necessary to better understand the long-term effects.

Dupilumab in chronic rhinosinusitis with nasal polyps: Real life data in a multicentric Sicilian experience.

OBJECTIVE: This study aimed to evaluate the effectiveness and safety of dupilumab during the first year of treatment in a real-life setting, focusing on improvement in nasal polyp score (NPS) as well as specific symptoms, quality of life and olfactory function. METHODOLOGY/PRINCIPAL: A multicentric observational cohort study was carried out. A total of 170 patients were enrolled in the Otorhinolaryngology Unit of the three University Hospitals and considered for dupilumab therapy. All recorder characteristics were age (at the first dupilumab application visit), sex, smoke habits, previous local and systemic corticosteroid therapy, history of endoscopic sinus surgery, number of previous endoscopic sinus surgery, concomitant asthma, history of an allergic condition, immunoglobulin E (IgE), allergy to nonsteroidal anti-inflammatory drugs (NSAIDs), Aspirin Exacerbated Respiratory Disease (AERD), other comorbidities associated, blood eosinophils, nasal polyp score, sinonasal outcome test 22 (SNOT 22), sniffin' stick test, the start date of dupilumab therapy and number of doses of dupilumab and eventually, Dupilumab's adverse events related to administration. The Wilcoxon test for dependent samples was performed to compare variables. Statistical significance was assumed for p values < 0.05. RESULTS: A statistically significant reduction in SNOT-22 and NPS was shown at the 6th and 12th month compared to baseline values (p < 0.001 for both comparisons). A statistically significant increase value at the Sniffin' sticks test was shown in the 6th and 12th month compared to baseline values (p < 0.001 for both comparisons). At the 12-month follow-up, according to EUFOREA indications, all patients were considered to remain in treatment with dupilumab and continued the treatment because of a reduced NPS, improved quality of life and a reduced need for system corticosteroids. Dupilumab seemed to be well tolerated by all patients. Any adverse effect of the drug led to the quit of biological treatment. CONCLUSIONS: This multi-centric real-life study supported the effectiveness of dupilumab as an add-on therapy to intranasal corticosteroids in patients with severe uncontrolled CRSwNP in improvement of quality of life, severity of symptoms, polyp size reduction and smell function. Furthermore, our data support the safety profile of monoclonal therapy with dupilumab.

Circulating ILC precursors expressing CD62L exhibit a type 2 signature distinctly decreased in psoriatic patients.

Human CD117+ CRTH2neg innate lymphoid cells (ILC) comprise multipotent precursors (ILCp), which are able to differentiate into subtypes in response to different signals received in peripheral tissues. NKp46+ ILCp have been reported to associate with ILC3 whereas KLRG1+ ILCp with ILC2, although the latter can also generate other ILC subsets, thus, maintaining a substantial plasticity. We here showed that CD62L is expressed by ILCp exclusively within KLRG1+ population and its expression marks a loss of their broad differentiation potential. Analysis of cytokine production and relevant markers demonstrated that CD62L+ ILCp mainly differentiate into ILC2 whereas CD62Lneg counterpart can also differentiate into other ILC subsets depending on the signals they receive. Remarkably, in peripheral blood of psoriatic patients, where ILC3 are usually enriched, CD62L+ ILC were drastically reduced, whereas CD62Lneg ILC2 upregulated both RORγt and NKp46, thus, suggesting an ongoing conversion to ILC3. Therefore, CD62L now emerges as a potential marker to identify a skewing toward type 2 among ILCp.

Extended wear hearing aids: a comparative, pilot study.

PURPOSE: The study evaluated if there were differences between three types of hearing aids, Lyric extended wear (EW), receiver-in-the-ear canal (RITE), completely-in-the-canal (CIC) hearing aids in terms of audiological and psychosocial outcomes. METHODS: Fifteen patients were selected. INCLUSION CRITERIA: Pure-Tone Average (PTA) air conduction range of hearing threshold at 500, 1000, and 2000 Hz from 15 dB HL to 75 dB HL. Patients were assigned in three groups according to the hearing aid used: Extended wear, RITE, and CIC. Pure-tone audiometry, speech audiometry, free-field pure-tone and speech audiometry with hearing aids, and Matrix sentence test were performed. The Satisfaction with Amplification in Daily Life (SADL) questionnaire and the Abbreviated Profile of Hearing Aid Benefit (APHAB) questionnaire were used to assess the psychosocial and audiological benefits provided by hearing aids. RESULTS: No differences were demonstrated in the Matrix sentence test between the groups. A statistically significant difference was present between the "Personal image" of patients with EW and RITE with a p value of 0.01 (better outcome using EW). For the APHAB questionnaire, a significant difference was present in the "Aversiveness" of the patients with EW in comparison to CIC and RITE with a p value of 0.01 (higher aversiveness of sound using EW). CONCLUSION: In terms of audiological advantage, extended ear hearing aids are similar to RITE and CIC as demonstrated from the Matrix speech reception threshold. The result was confirmed using the APHAB questionnaire. Extended wear devices are better than daily hearing aids concerning the "personal image".

Frequency-lowering processing to improve speech-in-noise intelligibility in patients with age-related hearing loss.

OBJECTIVE: Modern hearing aids use various signal-processing strategies to improve speech intelligibility. In this manuscript, we studied the linear frequency transposition (LFT), a frequency-lowering algorithm, in patients with age-related hearing loss. Frequency-lowering algorithms transpose high-frequency sounds to a lower-frequency band. The study aimed to assess whether LFT could be used as a tool to improve speech intelligibility in patients with a better high-frequency preservation. METHODS: The study population consisted of 77 patients (age average 74.8 ± 12.4) wearing hearing aids with an open or tulip coupling system with age-related hearing loss. The unaided air conduction pure tone average (PTA) at 500, 1000, 2000 Hz was 43.5 ± 14.3 dB; the unaided word recognition score (WRS) average was 53.7 ± 12.5%. We compared WRS in all patients with the hearing aid turned on, in "quiet" and using a "pink" and "babble" masking noise. Three hearing aid settings were tested in each acoustic conditions: no transposition (NT), high transposition (HT), and low transposition (LT). "High" and "low" refer to the "start frequency"; all sounds above the start frequency are transposed in a lower-frequency band. When the start frequency was suggested by the fitting software, we called the condition "high transposition"; when the start frequency was set at the lowest possible value provided by the fitting software, we called the condition "low transposition". The quality of the voice was also assessed asking the patient to give a score from 1 to 10, where 10 was the maximum listening comfort [quality of voice score (QVS)]. RESULTS: Collected data were compared for each condition (NT, HT, LT, in quiet, pink noise and babble noise) and no statistically significant differences were found in WRS and QVS (quiet WRS p = 0.07, pink noise WRS p = 0.18, babble noise WRS p = 0.11, QVS p = 0.91). We selected 33 patients with a better WRS in babble noise using transposition (high and low). In this group, the age was significantly lower than patients who did not use transposition (p = 0.01). CONCLUSION: Linear frequency transposition is not useful to improve speech-in-noise intelligibility in patients with age-related hearing loss. Despite that no statistically significant differences were found, younger people could get advantages from the LFT when babble noise disturbs the listening of speech. The use of FL algorithm as a way to improve speech intelligibility in noisy environments should be always considered.

Preoperative Management of a Jehovah's Witness Patient Undergoing Head and Neck Surgery With High Risk of Bleeding.

ABSTRACT: Surgery in head and neck district is often associated with bleeding as major complication and need of blood transfusions. Homologous blood transfusions may be unacceptable to some patient groups such as the Jehovah's Witness (JW) patients. Refusal of potentially life-saving treatment creates ethical dilemmas for treating clinicians.This is the first report in literature which examines the management and treatment of a female JW patient who underwent major surgical procedure for squamous cell carcinoma of the jaw with a high risk of hemorrage which rejected any possibility of blood and hemocomponent transfusion by virtue of her religious principles.

Symptomatology in head and neck district in coronavirus disease (COVID-19): A possible neuroinvasive action of SARS-CoV-2.

OBJECTIVE: The aim of this manuscript is to investigate transversally Ear Nose Throat (ENT) symptoms COVID-19 infection correlated and to study the neurotropism and neuroinvasiveness of the virus in the head-neck district through the investigation of the sense of smell, taste, tearing, salivation and hearing. METHODS: A total of 50 patients with laboratory-confirmed COVID-19 infection were included in our study. For each patient we evaluated the short version of the Questionnaire of Olfactory Disorders-Negative Statements (sQOD-NS), the Summated Xerostomia Inventory-Dutch Version (SXI-DV), The Standardized Patient Evaluation of Eye Dryness (SPEED), Schirmer test I, the Hearing Handicap Inventory For Adults (HHIA) and the Tinnitus Handicap Inventory (THI). All the tests we carried out were performed during the active phase of the symptomatology from COVID-19 (Condition A) and 15 after SARS-COV-2 RT-PCR test negative (Condition B). RESULTS: A total of 46 patients (92%) had olfactory dysfunction related to the infection. The 70% of patients reported gustatory disorders. Cough, fever, headache and asthenia were the most prevalent symptoms. There was a statistically significant difference (p < 0,001) in sQOD-NS, SXI-DV, SPEED, Schirmer test, HHIA and THI between Condition A and Condition B. CONCLUSIONS: In our population there was an alteration of the sense of taste, of the sense of smell, dry eyes and of the oral cavity and an auditory discomfort, symptoms probably linked to the neurotropism of the virus. Furthermore, anosmia, dysgeusia and xerostomia are early symptoms of COVID-19, which can be exploited for an early quarantine and a limitation of viral contagion.

Real ear measurement (REM) and auditory performances with open, tulip and double closed dome in patients using hearing aids.

OBJECTIVE: The aim of the study is to evaluate the importance of acoustic modifications generated by different commercially available ear-tips, focused on domes of receiver in the canal hearing aids using Real Ear Measurement (REM). METHODS: We enrolled 110 people selecting 200 ears bearers of hearing aids. In every patient, we performed REM and audiological tests with three different dome types: Open, Tulip and Double Closed (DC). Data about real-ear occluded gain (REOG), Pure Tone Average (PTA), Word Recognition Score (WRS) with aids switched on in Free Field, Ear and Auditory Comfort were collected and analyzed. RESULTS: REOG gain was statistically significant different between the three types of dome, with a DC that always closes the external auditory canal (EAC) (p < 0.001). There was no statistically significant difference between the PTA (p = 0.11). Regarding the WRS there were statistically significant differences between Open and DC dome (p < 0.001) and between Tulip and DC dome (p < 0.001), with worse discrimination when using DC. Both auditory and ear comfort are worse in the DC than in the other two domes (p < 0.001). From measured REOG gain values, in 135 cases Tulip dome does not occlude the EAC, with a statistically significant difference compared to DC (p < 0.001; Odd Ratio 0.0012; 95% CI 0.001-0.0196). CONCLUSION: Our study confirms the necessity to perform REM to evaluate if the prescription target is achieved, especially when tulip domes are used, because they may not occlude the ear canal, causing in some cases the reduction of the vocal discrimination.

Nasopharynx Hairy Polyp as a Cause of Stridor in Newborn.

Hairy polyps are histological benign lesions derived from 2 germinal layers which arise during fetal period, they can occur anywhere in the body. When they are localized in the oropharynx or nasopharynx can lead to upper airway obstruction in infants.We describe a case of a 2-days-old full-term female with intermittent upper airway obstruction, stridor, and feeding difficulty. Endoscopic and radiologic exams show a mass localized in nasopharynx, which was excised with a transnasal endoscopic approach resolving her respiratory difficulties.Histology confirmed the diagnosis of hairy polyp, a mass composed by an external layer of mature skin and a core with subcutaneous mature fibro fatty tissue, mature skeletal muscle, and cartilage.This report has an important value for the readers because, for a good functional result and an excellent prognosis, an accurate clinic and radiologic diagnose, with subsequent surgical complete resection should be performed.

Rhino-Orbito-Cerebral Mucormycosis in Diabetic Disease Mucormycosis in Diabetic Disease.

The authors present their experience about clinical evidences that include patients with an untreated diabetes who developed rhino-orbito-cerebral mucormycosis (ROCM). They were treated with endoscopic sinus surgery and medical treatment with intravenous, intradural therapy, and sinus washes with amphotericin B. The ROCM is a disease with a rapid evolution and an increase in mortality rate, especially if the fungus enters the cranial cavity. Therefore, it would be necessary in all diabetic patients with sinus symptoms, headaches, visual changes, suspect a mucormycosis, and perform a careful radiology assessment and a nasal endoscopy. Often, despite an early diagnosis and rapid treatment for ROCM, it is not possible to stem the disease, which ends with the patient's death.

Looking toward predicting functional recovery in disorders of consciousness: can sensorimotor integration help us?

PRIMARY OBJECTIVE: Only a few objective prognostic markers are available for patients with disorders of consciousness (DoC). We assessed whether the magnitude of short-latency afferent inhibition (SAI) might be a useful predictor of responsiveness recovery and functional outcome in patients with DoC. RESEARCH DESIGN: We enrolled 40 patients with prolonged Minimally Conscious State (MCS) and Unresponsive Wakefulness Syndrome (UWS) in a longitudinal, observational study. METHODS AND PROCEDURES: Clinical features (including Coma Recovery Scale-Revised, CRS-R, and Glasgow Outcome Scale, GOS) and SAI were collected at the study entry and after 18 months from study inclusion, to assess a correlation between SAI and the clinical outcome. MAIN OUTCOMES AND RESULTS: At the follow-up, 19 patients remained in their baseline condition, whereas 7 UWS evolved into MCS or emerged-from-MCS (EMCS), eight MCS evolved into EMCS, and two MCS- evolved into MCS+. Two UWS and one MCS+ died for cardiopulmonary complications. The patients who showed the highest GOS, the highest CRS-R and the lowest SAI strength at study entry, improved at the follow-up. CONCLUSIONS: Our findings suggest that an objective and simple neurophysiologic measure as SAI strength could provide useful information to predict the outcome and the behavioral responsiveness of patients with DoC.

Cerebrospinal Fluid Leak Following Nasal Packing for Epistaxis.

Anterior epistaxis is commonly treated with Merocel nasal packing insertion. A 63-year-old male patient showed a cerebrospinal fluid rhinorrhea and pneumocephalus immediately after insertion of a Merocel tampon used for spontaneous right anterior epistaxis. He later developed fever and headache. This clinical report is to highlight how the nasal merocel should be positioned by specialized personnel and to describe how to manage this type of complication.

Vaccine composition formulated with a novel TLR7-dependent adjuvant induces high and broad protection against Staphylococcus aureus.

Both active and passive immunization strategies against Staphylococcus aureus have thus far failed to show efficacy in humans. With the attempt to develop an effective S. aureus vaccine, we selected five conserved antigens known to have different roles in S. aureus pathogenesis. They include the secreted factors α-hemolysin (Hla), ess extracellular A (EsxA), and ess extracellular B (EsxB) and the two surface proteins ferric hydroxamate uptake D2 and conserved staphylococcal antigen 1A. The combined vaccine antigens formulated with aluminum hydroxide induced antibodies with opsonophagocytic and functional activities and provided consistent protection in four mouse models when challenged with a panel of epidemiologically relevant S. aureus strains. The importance of antibodies in protection was demonstrated by passive transfer experiments. Furthermore, when formulated with a toll-like receptor 7-dependent (TLR7) agonist recently designed and developed in our laboratories (SMIP.7-10) adsorbed to alum, the five antigens provided close to 100% protection against four different staphylococcal strains. The new formulation induced not only high antibody titers but also a Th1 skewed immune response as judged by antibody isotype and cytokine profiles. In addition, low frequencies of IL-17-secreting T cells were also observed. Altogether, our data demonstrate that the rational selection of mixtures of conserved antigens combined with Th1/Th17 adjuvants can lead to promising vaccine formulations against S. aureus.

Therapeutic efficacy of the Galletti-Contrino manoeuvre for benign paroxysmal positional vertigo of vertical semicircular canals in overweight subjects.

OBJECTIVE: To compare the Galletti-Contrino manoeuvre with the more widely used Semont-Toupet in overweight subjects presenting with benign paroxysmal positional vertigo (BPBV) of vertical semicircular canals (posterior and anterior canals). STUDY DESIGN: Prospective cohort study. PATIENTS: 204 patients (BMI range 25-30) with a diagnosis of BPPV of vertical semicircular canals were randomly divided in two groups treated with two different maneuvers: Galletti-Contrino (Group A) and Semont-Toupet manoeuvre (Group B). The results were compared with those obtained from a control group (204 non-overweight subjects with BPV of vertical semicircular canals.) INTERVENTION: Galletti Contrino/ Semont Toupet manoeuvres. MAIN OUTCOME MEASURE(S): Liberatory nystagmus or vertigo after maximum 2 maneuvers. Vertigo and dizziness intensity scores (Visual analogue scale VAS 0-10) from day 0 to day 5 following the repositioning manoeuvre were also recorded in responsive patients. RESULTS: While in non-overweight subjects no significant difference comparing the effectiveness of the two manoeuvres was found, liberatory nystagmus and vertigo were more frequently observed after Galletti Contrino manoeuvre in overweight subjects; this difference was statistically significant when posterior canals were involved (P < 0.03). Vertigo and dizziness VAS scores reduced significantly from day 0 to day 5 after therapy in all groups. A more significant reduction of dizziness VAS was recorded in patients undergoing Galletti-Contrino manoeuvre at days 4-5 (P < 0.005). CONCLUSION: Galletti-Contrino manoeuvre seems to be significantly more effective than Semont-Toupet manoeuvre in the treatment of BPPV of posterior semicircular canal and may be preferential in patients with limited body movements.

Relation among Psychopathological Symptoms, Neuropsychological Domains, and Functional Disability in Subacute Poststroke Rehabilitation.

BACKGROUND: Neuropsychiatric disorders are commonly observed in patients following a stroke. Among 30%-60% of poststroke patients suffer from depression and anxiety (18%-25%). Some authors suggest an association between psychological symptoms and lesions in specific brain areas. In particular, lesions in left frontal cortex and left basal ganglia are frequently associated with poststroke depression and with comorbidity of anxiety and depression, whereas isolated anxiety symptoms are frequently observed after right hemispheric lesions. METHODS: We investigated the relationship between depressive symptoms and anxiety in patients with subacute stroke and lesion side, motor disability, and cognitive impairment. We enrolled 100 patients undergoing a rehabilitative program within 1-3 months after a first-onset stroke. RESULTS: Our patients presented mild to moderate depressive and anxious symptoms after stroke. In the comparison between patients with right and left lesions, during subacute poststroke phase, we did not find a specific link between existence of psychiatric symptoms and lesion side. However, in left lesion, depression correlated with age and alteration in delayed memory and attention, whereas memory deficit influenced anxiety symptoms. On the contrary, in right lesion, depressive symptoms were associated with attention ability, whereas anxiety was related to memory and attention. Depression and anxiety were not related to degree of neurological and functional deficits. CONCLUSIONS: The comorbidity between stroke and psychopathological disorders has been recognized as syndrome and should be diagnosed early and treated in order to improve the quality of life of patients and caregivers, and to improve rehabilitative process.

Computerized Training in Poststroke Aphasia: What About the Long-Term Effects? A Randomized Clinical Trial.

BACKGROUND: Poststroke aphasia is a very disabling disorder, which may affect speech expression, comprehension, and reading or writing. Treatment of aphasia should be initiated as soon as possible after the brain injury; however, the improvement of language functions can occur also in the chronic phase. MATERIALS AND METHODS: Thirty-two patients were randomly assigned to either an experimental group (17 patients) treated with computerized rehabilitation training (Power-Afa, Maddaloni, Campania, Italy) or a control group (15 patients), submitted to conventional speech therapy. Patients were trained 3 times a week for 8 weeks, (i.e., 24 sessions of 45 minutes each), and assessed at baseline (T0), at the end of each training (T1), and 3 months after the end of the treatment (T2). RESULTS: The experimental group had a significant improvement from T0 to T1 in all the outcomes, whereas for the control group patients such an improvement was significant only concerning Functional Independence Measure and ideomotor praxis. Notably, the improvements in cognitive and language functions were maintained at 3-month follow-up only in the experimental group. CONCLUSIONS: The software Power-Afa can be considered a valuable tool in improving the linguistic and cognitive recovery in patients affected by poststroke aphasia in the chronic phase. Further studies with larger samples and longer follow-up periods are needed to confirm such promising findings.

Neonatal stridor and laryngeal cyst: Which comes first?

Neonatal stridor is a rare condition usually caused by laryngomalacia. Congenital laryngeal cyst represents an uncommon cause of stridor in the neonatal population and may be misinterpreted as laryngomalacia, leading to serious morbidity and mortality if diagnosis and treatment are delayed. Herein we report the case of a full-term infant with stridor, feeding problems and failure to thrive. Initially, direct laryngoscopy diagnosed only laryngomalacia. As stridor worsened, however, and respiratory distress appeared, repeat laryngoscopy showed vallecular laryngeal cyst, visible macroscopically. The patient was successfully treated with endoscopic marsupialization. There was no evidence of recurrence at follow up after 3 months. This case highlights the importance of laryngoscopic assessment for suspected laryngeal abnormalities in infants with stridor. If symptoms worsen, endoscopy should be repeated, because congenital laryngeal cysts may not be immediately visible macroscopically.

Tongue reduction for OSAHS: TORSs vs coblations, technologies vs techniques, apples vs oranges.

Coblation tongue surgery and Trans-oral robotic surgery (TORS) proved to be the most published therapeutical options for the treatment of patients affected by obstructive sleep apneas (OSAHS). A systematic review of the literature and an analysis of the data are presented. The mean rates of failure were 34.4 and 38.5 %, respectively in TORS and Coblation groups. Complications occurred in 21.3 % of the patients treated with TORS and in 8.4 % of the patients treated with Coblation surgery. TORS seems to give slightly better results, allowing a wider surgical view and a measurable, more consistent removal of lingual tissue. However, the higher rate of minor complication and the significant costs of TORS must also be considered. Moreover, both technologies may be applied to a wide range of surgical techniques, each of them with different effectiveness.

Four-component Staphylococcus aureus vaccine 4C-staph enhances Fcγ receptor expression in neutrophils and monocytes and mitigates S. aureus infection in neutropenic mice.

Staphylococcus aureus is a human bacterial pathogen causing a variety of diseases. The occurrence of multidrug-resistant strains of Staphylococcus aureus underlines the need for a vaccine. Defining immune correlates of protection may support the design of an effective vaccine. We used a murine Staphylococcus aureus infection model, in which bacteria were inoculated in an air pouch generated on the back of the animal. Analysis of the air-pouch content in mice immunized or not with an adjuvanted multiantigen vaccine formulation, four-component S. aureus vaccine (4C-Staph), prior to infection allowed us to measure bacteria, cytokines, and 4C-Staph-specific antibodies and to analyze host immune cells recruited to the infection site. Immunization with 4C-Staph resulted in accumulation of antigen-specific antibodies in the pouch and mitigated the infection. Neutrophils were the most abundant cells in the pouch, and they showed the upregulation of Fcγ receptor (FcγR) following immunization with 4C-Staph. Reduction of the infection was also obtained in mice immunized with 4C-Staph and depleted of neutrophils; these mice showed an increase in monocytes and macrophages. Upregulation of the FcγR and the presence of antigen-specific antibodies induced by immunization with 4C-Staph may contribute to increase bacterial opsonophagocytosis. Protection in neutropenic mice indicated that an effective vaccine could activate alternative protection mechanisms compensating for neutropenia, a condition often occurring in S. aureus-infected patients.