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Background/objectives: Otosclerosis is a relatively uncommon condition that causes conductive hearing loss in children. The preferred treatment for adults is stapedotomy, while for individuals under 18 years old, there is an ongoing discussion about the best treatment approach. Thus, the surgical procedure for the stapes in pediatric patients continues to be a subject of debate. This study aimed to evaluate the results of stapes surgery in children, trying to understand, based on our results, whether this is actually the most suitable option., Methods: The study included 18 patients who underwent surgery between January 2013 and December 2023. The patients' ages ranged from 11 to 18 years, with an average age of 14.7. Out of the total 21 surgeries, three patients opted for bilateral surgery. Pre- and post-operative data were compared, focusing on the mean air conduction (AC) and bone conduction (BC) thresholds at frequencies of 0.5, 1, 2, and 4 kHz. Additionally, pre-operative thresholds and the post-operative air-bone gap (ABG) were examined., Results: After a year, the air-bone gap was effectively reduced to 10 dB or less in 94% of the 21 cases, and to 20 dB or less in 98% of all cases., Conclusions: Our results and research in the field have consistently shown that stapedotomy, when conducted by skilled otosurgeons, is a reliable and successful procedure for a considerable number of patients. The outcomes it generates are similar to those achieved through the procedure conducted during adulthood.

The authors present the case of a young boy who experienced progressive unilateral hearing loss initially believed to be unrelated to any other medical condition. Methods: The patient received a thorough evaluation, which included a comprehensive battery of audiological tests, a CT scan, and a gadolinium-enhanced MRI. Results: A repeated imaging investigation revealed the presence of a mass that mimicked a vestibular schwannoma (VS), but despite this, the boy was ultimately diagnosed with cerebral manifestations of B-cell acute lymphoblastic leukemia (B-ALL). Conclusions: Cerebral lesions originating from the internal auditory canal are rare in cases of B-ALL. In this case, the initial signs and symptoms of the disease were solely related to the audiovestibular system, making the diagnostic process particularly complicated. Unilateral hearing loss cases may indicate the presence of potentially life-threatening conditions, even if the hearing loss appears to be clinically non-syndromic. For these reasons, unilateral hearing losses necessitate a comprehensive interdisciplinary diagnostic approach from the very start of auditory manifestation and, in particular, if the hearing impairment demonstrates threshold progression.

Given the crucial role of the personalized management and treatment of hearing loss (HL), etiological investigations are performed early on, and genetic analysis significantly contributes to the determination of most syndromic and nonsyndromic HL cases. Knowing hundreds of syndromic associations with HL, little comprehensive data about HL in genomic disorders due to microdeletion or microduplications of contiguous genes is available. Together with the description of a new patient with a novel 3.7 Mb deletion of the Xq21 critical locus, we propose an unreported literature review about clinical findings in patients and their family members with Xq21 deletion syndrome. We finally propose a comprehensive review of HL in contiguous gene syndromes in order to confirm the role of cytogenomic microarray analysis to investigate the etiology of unexplained HL.

Hyperventilation induces metabolic changes that can elicit nystagmus (hyperventilation-induced nystagmus, HVIN) in various vestibular disorders, revealing vestibular imbalance and bringing out central or peripheral asymmetries. In acute unilateral vestibulopathy (AUVP, namely vestibular neuritis), hyperventilation can induce different patterns of nystagmus (excitatory, inhibitory, or negative), disclosing or modifying existing static vestibular asymmetries through its ability to invalidate compensation or increase peripheral excitability. In this context, we followed the evolutionary stages of HVIN in AUVP across 35 consecutive patients, with the goal of assessing alterations in the oculomotor pattern caused by hyperventilation over time. In the acute phase, the incidence of the excitatory pattern (and the strongly excitatory one, consisting of a reversal nystagmus evoked by hyperventilation) was significantly higher compared to the inhibitory pattern; then, a progressive reduction in the incidence of the excitatory pattern and a concomitant gradual increase in the incidence of the inhibitory one were observed in the follow-up period. Assuming the role of the ephaptic effect and the transient loss of vestibular compensation as opposing mechanisms, i.e., excitatory and inhibitory, respectively, the oculomotor pattern evoked by hyperventilation is the result of the interaction of these two factors. The data obtained allowed us to hypothesize an interpretative model regarding the pathogenetic aspects of responses evoked by hyperventilation and the etiologies of the disease: according to our hypotheses, the excitatory pattern implies a neuritic (viral) form of AUVP; instead, the inhibitory (and negative) one can be an expression of both the neuritic (viral) and vascular forms of the disease.

Objectives: Communicating in noisy settings can be difficult due to interference and environmental noise, which can impact intelligibility for those with hearing impairments and those with normal hearing threshold. Speech intelligibility is commonly assessed in audiology through speech audiometry in quiet environments. Nevertheless, this test may not effectively assess hearing challenges in noisy environments, as total silence is rare in daily activities. A recently patented method, known as the SRT50 FAST, has been developed for conducting speech audiometry in noise. This new method enables the acceleration and simplification of free field speech audiometry tests involving competition noise. This study aims to establish normative scores and standardize the SRT50 FAST method as a test for evaluating speech perception in noise in pediatric patients., Methods: The study included 30 participants with normal hearing, consisting of 11 females and 19 males, ranging in age from 6 to 11 years. A series of speech audiometry tests were conducted to determine the speech reception threshold 50% (SRT50) in competing conditions. This included testing both the fast mode (SRT50 FAST) currently being studied and the traditional method (SRT50 CLASSIC). The SRT50, or Signal to Noise Ratio (SNR) at which 50% of speech recognition occurred, was investigated for both methods., Results: The mean SRT50 FAST test score was -2.69 (SD = 3.15). The dataset exhibited a normal distribution with values ranging from 3.60 to -8.60. Since the scores are expressed in SRT, higher scores indicate poorer performance. We have established a threshold of 3.60 as the upper limit of the normal range, therefore, patients with scores above this threshold are considered to have abnormal results., Conclusions: This study aimed to establish normative data for the evaluation of free field speech in noise recognition using the SRT50 FAST method in the pediatric population. This method accurately investigates the necessary signal-to-noise ratio for achieving 50% recognition scores with bisyllabic words in a quick manner. The ultimate objective is to employ this test to identify the optimal configuration of hearing rehabilitation devices, particularly for pediatric patients with hearing aids and/or cochlear implants. Additionally, it can be used to assess pediatric patients with unilateral hearing loss., Competing Interests: Declaration of competing interest The authors certify that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Migraine pathogenic pathways may selectively target the cochlea. A qualitative and quantitative analysis of cochlear symptoms in migraine patients without vestibular migraine and/or Méniere's disease was conducted. We examined 60 consecutive patients with history of cochlear symptoms, including fullness, tinnitus, and hearing loss. Patients were divided into two groups based on migraine history: M (migraine) and nM (no migraine). The incidence of migraine was compared to a homogeneous control group with dysfunctional and inflammatory dysphonia without cochlear symptoms. The type, time of onset, recurrence, bilaterality of symptoms, and hearing threshold were analyzed. The incidence of migraine was significantly higher ( p = 0.04) in patients with cochlear symptoms than in the control group. The onset of symptoms is significantly earlier ( p < 0.05) in the presence of migraine. The fullness, recurrence, and bilaterality of symptoms are associated with migraine in a statistically significant way ( p < 0.05). Pure tone audiometry shows a statistically significant increase in the hearing threshold (500-1000 Hz) in group M. Based on developing findings, cochlear migraine may be considered as a novel clinical entity, like vestibular migraine. It would be the expression, in the absence of vertiginous symptoms, of a selective suffering of the anterior labyrinth by known operating mechanisms of migraine.

Ototoxic drugs can result in hearing loss and tinnitus. Early detection of the ototoxic process can help minimize or prevent these consequences. The American Speech-Language-Hearing Association has provided guidelines for monitoring ototoxicity, whereas Italy has not yet implemented a national monitoring protocol. This study aims to assess the current state of ototoxicity monitoring in patients receiving cisplatin therapy. A self-administered survey has been used to gather information from oncologists, audiologists, and ENT specialists. The research was conducted at Santa Maria della Misericordia hospital in Perugia. Two questionnaires were administered, one to ENT/audiology specialists and another to oncology specialists. Both questionnaires were used to collect information on awareness of chemotherapy-induced ototoxicity. A comprehensive understanding of cisplatin-induced ototoxicity has been widely established (100%). The most commonly reported audiological symptoms by patients were hearing loss (100%) and tinnitus (87.5%). The majority of ENT and audiologists (93.8%) and oncologists (92.9%) expressed the need for a specific ototoxic monitoring program. However, they noted the absence of a well-defined ototoxicity monitoring protocol. A well-established and efficient ototoxic monitoring system facilitates early detection of ototoxic hearing loss and subsequent rehabilitation of inevitable hearing impairment.

Far-advanced otosclerosis (FAO) refers to severe otosclerosis with scarce auditory functions. The identification of the best method to correctly listen to sound and speech has a large impact on patients' quality of life. We retrospectively analyzed the auditory function of 15 patients affected by FAO who were treated with stapedectomy plus hearing aids independent of the severity of their auditory deficit before surgery. The combination of surgery and hearing aids allowed excellent recovery of the perception of pure tone sounds and speech. Four patients, because of poor auditory thresholds, needed a cochlear implant after stapedectomy. Despite being based on a small sample of patients, our results suggest that stapedotomy plus hearing aids could improve the auditory capacities of patients with FAO independent of their auditory thresholds at T0. The careful selection of patients is fundamental to obtain the best outcomes.

Objective: To assess newborn hearing screening (NHS) impact on timing of cochlear implant (CI) surgery of patients with prelingual bilateral profound hearing impairment (BPHI), in order to evaluate whether the NHS ultimately serves the needs of the target population in Italy., Methods: An online questionnaire was created to survey subjects affected by prelingual BPHL born between 1990 and 2018. Questions focused on age at BPHI diagnosis, first and second CI surgery (if performed), and the region in which the surgery was performed. The survey was distributed to potential participants via social media communities used by hearing impaired people or their family members for sharing advice and offering support. Responses were analyzed using descriptive statistics., Results: Among the 318 respondents who completed the questionnaire, 276 (87%) reported having chosen CI surgery, 2/3 of them bilaterally. In the vast majority (97%) of cases the CI is used on a daily basis. Most of the people residing in the center (65%) and southern Italy (71%) had to move from their region of residence to perform the surgery. Late CI surgery was associated with failure to perform NHS ( p  = 0.007), birth before 2011 ( p  = 0.009), definitive diagnosis of BPHI after 6 months of life ( p  = 0.002), and progressive hearing impairment ( p  < 0.001)., Conclusion: The worldwide scientific approval of the NHS as the current best opportunity for early diagnosis and CI treatment for prelingual BPHI is confirmed by what patients and families reported via the online questionnaire used for this study. In recent years, early bilateral cochlear implantation has become increasingly available in Italy, but late diagnosis, progressive hearing loss, failure to perform the NHS and lack of follow-up are still open questions. A large proportion of families had to move from the region of residence to have their child undergo CI surgery, revealing inequalities in terms of geographical disparities. Social media has proved to be a valuable, fast and inexpensive tool for gathering information on the effectiveness of health prevention programs, involving a large sample of individuals in a short amount of time., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Orzan, Pizzamiglio, Magadle, Bubbico, Cutler, Consolino, Burdo, Zamagni, Magni, Mariottini, Gambacorta, Ricci and Brotto.)

Hearing impairment is the most frequent of the sensorial defects in humans, and if not treated promptly, can severely impair cognitive and spoken language skills. For this reason, a universal newborn hearing screening (UNHS) has been established. The purpose of our study is to examine, by means of a retrospective analysis, the results of the UNHS program in the Umbria region during the spread of COVID-19 (2020-2021), comparing the same data from the years 2011-2012, to understand if the program has improved. Our study has shown how the coverage rate of well born babies' (WB) screening has significantly increased to currently meet the JCIH benchmark. The percentage of WB referrals significantly decreased in 2020-2021, another indicator of the screening program's greater efficiency in Umbria. However, a critical issue has emerged: the percentage of those lost to follow-up is greater than 30%, well above the benchmark. As far as the COVID-19 pandemic has certainly had a significant impact, it is necessary to carefully monitor those who do not access the diagnostic level. To emphasize the importance of a proper screening program, it will be helpful to strengthen the computerized data collection system and create an information network between audiologists, pediatricians and families.

Benign Paroxysmal Positional Vertigo (BPPV), Vestibular Migraine (VM), and Meniere Disease (MD) are among the most common episodic vestibulopathies. Persistent Postural Perceptual Dizziness (PPPD) is a chronic functional vestibular disorder that can arise in patients suffering from one or more of these conditions. We analyzed the role of these vestibular disorders as single or multiple associated comorbidities and as a precipitating condition for PPPD. A total of 376 patients suffering from dizziness with a known history of single or multiple vestibular disorders were preliminarily evaluated. We conducted a careful anamnesis to determine whether the reported dizziness could meet the diagnostic criteria for PPPD. PPPD was diagnosed in 24 cases; its incidence in patients with history of a single comorbidity or multiple vestibular comorbidities was 3.9% and 22.4%, respectively. BPPV, VM, and MD were identified as a precipitating condition in 2.34%, 16.45%, and 3.92%, respectively. BPPV constituted a precipitating condition mainly at the first episode. We observed that the presence of multiple vestibular comorbidities (BPPV, VM, and MD) in patients' clinical history increased the risk of PPPD. VM plays a significant role in representing a precipitating condition for PPPD, both when present individually or in association with the other vestibular disorders.

Purpose: This study aimed at identifying gender differences in the hearing thresholds in a sample of patients with otosclerosis before and after surgery to understand the impact of female hormones on auditory thresholds., Methods: This retrospective study analyzed 184 patients (123 women and 61 men) affected by otosclerosis. All the patients were affected by conductive hearing loss and treated by stapedoplasty. Auditory thresholds at the baseline (T0) and one month after surgery (T30) were collected. Air and bone thresholds and Air Bone Gap (ABG) were compared between females and males using one-way ANOVA., Results: Statistically significant differences were observed comparing the air threshold at T0 vs T30 both in women and men (p < 0.0001). No statistically significant differences were observed in the bone conduction thresholds before and after surgery. The comparison between females and males showed statistically significant differences both at T0 (p < 0.01) and T30 (p < 0.05) for air conduction thresholds and ABG at 4000 Hz., Conclusion: Although stapedoplasty reduced the difference between females and males in the air conduction thresholds and ABG, women showed better recovery of their middle ear function with better auditory thresholds and ABG. The female hormones might positively impact the ligaments of the incudostapedial joint improving chain flexibility. This benefit might explain the statistically significant difference observed in women at 4000 Hz before and after surgery., (© 2022. The Author(s).)

Immune escape represents a major driver of acute myeloid leukemia (AML) reemergence after allogeneic hematopoietic cell transplantation (allo-HCT), with up to 40% of relapses prompted by nongenomic loss of HLA class II expression in leukemia cells. By integrative analysis of gene expression, DNA methylation, and chromatin accessibility in paired diagnosis/relapse primary samples and in the respective patient-derived xenografts (PDX), we identify the polycomb repressive complex 2 (PRC2) as a key epigenetic driver of this immune escape modality. We report that loss of expression of HLA class II molecules is accompanied by a PRC2-dependent reduction in chromatin accessibility. Pharmacologic inhibition of PRC2 subunits rescues HLA class II expression in AML relapses in vitro and in vivo, with consequent recovery of leukemia recognition by CD4+ T cells. Our results uncover a novel link between epigenetics and leukemia immune escape, which may rapidly translate into innovative strategies to cure or prevent AML posttransplantation relapse., Significance: Loss of HLA class II expression represents a frequent mechanism of leukemia posttransplantation relapse. Here we identify PRC2 as the main epigenetic driver of this immune escape modality and show that its chemical inhibition can reinstate a proficient graft-versus-leukemia effect, providing an innovative rationale for personalized epigenetic immunotherapies. See related commentary by Köhler and Zeiser, p. 1410. This article is highlighted in the In This Issue feature, p. 1397., (©2022 The Authors; Published by the American Association for Cancer Research.)

Cochlear implant surgery in far-advanced otosclerosis can be challenging due to the degenerative process that affects the cochlea. We used OTOPLAN® to plan and define the details of surgery in a patient with such severe alteration of the cochlea that cochlear implant could be contraindicated. A 73-year-old man affected by bilateral far-advanced otosclerosis, previously treated by bilateral stapedotomy, presented 0% of speech discrimination using bilateral hearing aids. A unilateral cochlear implant was planned. The patient underwent radiologic investigation pre-surgery with temporal bone computer tomography, magnetic resonance imaging, and OTOPLAN. Radiology confirmed bilaterally advanced signs of fenestral and cochlear otosclerosis with large osteolytic cavities along the whole cochlea leading to the mixture of endolymph and perilymph. The OTOPLAN identified the alteration of the cochlea in detail. Based on the results of the software, we used a perimodiolar implant on the left ear. No intraoperative or post-operative surgical complications were observed. The patient was checked 6 months after surgery, he did not refer any problems and obtained 75% of speech discrimination at 65 dB. Our case suggests that OTOPLAN is a useful tool in far-advanced otosclerosis because careful planning of the surgery can positively affect the results. Despite the complexity of the anatomy, the software exactly described the real intrasurgical finding. We think that the use of OTOPLAN might improve the surgical indication.

A new non-invasive adhesive bone conduction hearing device (ABCD) has been proposed as an alternative solution for reversible bilateral conductive hearing loss in recurrent or long-lasting forms of otitis media with effusion (OME) in children that cannot undergo surgical treatment. Our aim was to assess the effectiveness of ABCD in children with OME. Twelve normal-hearing Italian-speaking volunteers, in whom a conductive hearing loss was simulated, participated in the study. The free-field average hearing threshold was determined and, to evaluate binaural hearing skills, loudness summation and the squelch effect were assessed. Five conditions were tested: (1) unaided without earplugs, (2) unaided with bilateral earplugs, (3) aided right ear with bilateral earplugs, (4) aided left ear with bilateral earplugs, and (5) bilateral aid with bilateral earplugs. Post-hoc analysis showed a significant statistical difference between plugged, unplugged, and each aided condition. The main results were a better loudness summation and a substantial improvement of the squelch effect in the bilaterally aided. Our results suggest that ABCD is a valid treatment for patients with conductive hearing loss that cannot undergo bone conduction implant surgery. It is also important to consider bilateral aids in order to deal with situations in which binaural hearing is fundamental.

Purpose: This study aimed to investigate the efficacy of taping in association with Kabat rehabilitation to ameliorate the outcomes of Bell's palsy., Methods: This case-control study was conducted on hospital-outbound patients. 20 patients over 18 years affected from Bell's palsy were recruited at the onset of the disease (< 5 days). Patients were simply randomized into two groups. Patients in group A underwent exclusively Kabat rehabilitation, while patients in group B were treated by combining facial taping and Kabat. Facial palsy severity was evaluated with ADS assessment at baseline (T0), 1 week (T1), 1 month (T2) and 3 months (T3) after treatment. One-way ANOVA was used to compare ADS scores variance between groups to evaluate differences between the two treatments., Results: Both groups presented statistically significant differences comparing the baseline with the other observational points (within analysis) (p < 0.0001). Patients in group B showed a statistically significant improvement compared to group A (between analyses) (p < 0.0001), especially at T2 (p < 0.01)., Conclusions: Facial taping combined with Kabat rehabilitation allowed to reduce the time of recovery and improved the outcomes of Bell's palsy.

Introduction: Arachnoid cyst in the internal auditory canal is a quite rare pathology but due to its compressive action on the nerves in this district should be surgically removed. Several surgical techniques have been proposed but no surgeons have used the minimally assisted endoscope retrosigmoid approach for its removal., Objective: To investigate the feasibility of using a minimally invasive endoscope assisted retro-sigmoid approach for surgical removal of arachnoid cysts in the internal auditory canal., Methods: Minimally invasive endoscope assisted retrosigmoid approach allows to access to the internal auditory canal through a minimally invasive retrosigmoid approach that combines the use of a microscope and an endoscope. It is performed in six steps: soft tissue step, bone step, dura step, cerebellopontine angle step (performed using an endoscope and a microscope), microscope-endoscope assisted arachnoid cysts removal and closure. We tested minimally invasive endoscope assisted retrosigmoid approach for removal of arachnoid cysts in the internal auditory canal on two human cadaveric heads (specimens) of subjects affected from audio-vestibular disorders and with arachnoid cysts in the internal auditory canal confirmed by magnetic resonance imaging., Results: The mass was completely and successfully removed from the two specimens with no damage to the nerves and/or vessels in the surgical area., Conclusion: The results of our study are encouraging and support the feasibility of using minimally invasive endoscope assisted retrosigmoid approach for removal of arachnoid cysts in the internal auditory canal. While further clinical in-vivo studies are needed to confirm the accuracy and safety of using the minimally invasive endoscope assisted retrosigmoid approach for this specific surgery, our group has successfully used the minimally invasive endoscope assisted retrosigmoid approach in the treatment of microvascular compressive syndrome, schwannoma removal and vestibular nerve resection., (Copyright © 2019 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.)

Working memory (WM) function can be reduced in patients suffering from unilateral hearing loss (UHL) and can affect their academic performance. We aimed to compare the WM abilities of three categories of children with UHL: patients implanted with hearing aids (HAs), patients receiving a bone-anchored hearing implant (BAHI), and subjects who did not receive hearing devices. A randomized clinical study, in which 45 children (mean age: 9.5 years) were evaluated by pure tone audiometry (to identify the side and the severity of the UHL), was conducted in a tertiary referral center. Patients were simply randomized into three groups: (1) children without HAs (No-HA group), (2) patients with a (digital) HA (HA group), and (3) children with a BAHI (BAHI group). Their working and short-term memories were studied in both noisy and silent conditions at the recruiting time (T0, baseline) and 6 months after (T1) the treatment. Statistical analyses were performed to analyze the variances between T0 and T1 within each group and between the three groups. The No-HA group improved its T1 WM scores in silence ( p < 0.01), but not in noise. The HA and BAHI groups showed statistically significant variances of T1 WM in noise ( p < 0.01 and p < 0.01, respectively). The HA and BAHI groups did not show statistically significant variances compared to T1. Our results suggest that hearing devices (HA and BAHI) in children with sensorineural UHL (SUHL) can improve WM capacity in noise. We speculate that bilateral hearing capacity might improve the quality of life of this population, especially during everyday activities where noise is present., (Copyright © 2020 della Volpe, Ippolito, Roccamatisi, Garofalo, De Lucia, Gambacorta, Longari, Ricci and Di Stadio.)

A correlation between inflammation and cancer has been identified in the case of nasal cancer, however a specific connection between nasal inflammation and extramedullary nasal plasmacytoma (ENP), to the best of our knowledge, has not yet been determined. The present case report describes a patient affected by ENP, in who the tumor arose in the same area, from which a nasal polyp was previously surgically removed, five months after the polyp excision. The patient underwent surgical endoscopic tumor asportation without being treated with radio-chemotherapy. ENP was totally removed via surgery and no signs of recurrence were identified by endoscopy or magnetic resonance imaging during the last check-up 1 year after tumor asportation. It was hypothesized that in this elderly patient, who was exposed to viral infections and pollution for several years, ENP may be correlated to the inflammatory process that occurred after surgery, and this likely contributed to a neoplastic mutation in B-cells., (Copyright: © Di Stadio et al.)

Over the last decade, the development of multiple strategies to allow the safe transfer from the donor to the patient of high numbers of partially HLA-incompatible T cells has dramatically reduced the toxicities of haploidentical hematopoietic cell transplantation (haplo-HCT), but this was not accompanied by a similar positive impact on the incidence of post-transplantation relapse. In the present review, we will elaborate on how the unique interplay between HLA-mismatched immune system and malignancy that characterizes haplo-HCT may impact relapse biology, shaping the selection of disease variants that are resistant to the "graft-vs.-leukemia" effect. In particular, we will present current knowledge on genomic loss of HLA, a relapse modality first described in haplo-HCT and accounting for a significant proportion of relapses in this setting, and discuss other more recently identified mechanisms of post-transplantation immune evasion and relapse, including the transcriptional downregulation of HLA class II molecules and the enforcement of inhibitory checkpoints between T cells and leukemia. Ultimately, we will review the available treatment options for patients who relapse after haplo-HCT and discuss on how a deeper insight into relapse immunobiology might inform the rational and personalized selection of therapies to improve the largely unsatisfactory clinical outcome of relapsing patients., (Copyright © 2020 Rovatti, Gambacorta, Lorentino, Ciceri and Vago.)

Purpose: This study aims to quantitatively compare the Jankovic assessment (JA) with electromyography (EMG)-based measures for assessing changes in facial movements in patients with facial dystonia., Materials and Methods: Thirteen patients (five males and eight females) affected with different forms of facial dystonia (hemifacial spasm and synkinesis) participated in this study. All patients were treated with Botulinum Toxin (BTX) and evaluated with the JA scale and EMG-based measures, including motor unit potentials (MUP) latency and presence of polyphasic potentials before and after BTX injection. Correlation between the JA scores and the EMG-based measures was calculated. Statistical analysis was performed with the Pearson test., Results: Correlation between the JA scores and the EMG-based measures was found to be statistically significant, both before and after treatment with BTX., Conclusion and Relevance: JA scores significantly correlated with more objective EMG-based measures, suggesting that the JA scale can be used to assess facial movement changes, for example elicited by a treatment such as BTX injection. Thus, in facial dystonia patients, the JA scale may be used for evaluating treatment outcomes as a valid and low-cost alternative to EMG., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Over the past decades, our molecular understanding of acute myeloid leukemia (AML) pathogenesis dramatically increased, thanks also to the advent of next-generation sequencing (NGS) technologies. Many of these findings, however, have not yet translated into new prognostic markers or rationales for treatments. We now know that AML is a highly heterogeneous disease characterized by a very low mutational burden. Interestingly, the few mutations identified mainly reside in epigenetic regulators, which shape and define leukemic cell identity. In the light of these discoveries and given the increasing number of drugs targeting epigenetic regulators in clinical development and testing, great interest is emerging for the use of small molecules targeting leukemia epigenome. Together with their effects on leukemia cell-intrinsic properties, such as proliferation and survival, epigenetic drugs may affect the way leukemic cells communicate with the surrounding components of the tumor and immune microenvironment. Here, we review current knowledge on alterations in the AML epigenetic landscape and discuss the promises of epigenetic therapies for AML treatment. Finally, we summarize emerging molecular studies elucidating how epigenetic rewiring in cancer cells may as well exert immune-modulatory functions, boost the immune system, and potentially contribute to better patient outcomes., (Copyright © 2019 Gambacorta, Gnani, Vago and Di Micco.)

Povidone-iodine is known for successfully treating surgical wounds; the combination between povidone-iodine and sugar, also called Knutson's formula, has been proposed to improve wound healing. Currently, no studies have investigated the effects of Knutson's formula to treat defects in wound closure following radio-chemotherapy in the head and neck region. The aim of this study is to evaluate the efficacy of Knutson's formula in improving the wound-healing process in patients who underwent radio-chemotherapy after surgery for head and neck cancer. The study, conducted from August 2013 to January 2017, included a sample of 34 patients (25 males and 9 females; age range: 60-75 years) treated with radio-chemotherapy after head and neck cancer surgery. All patients suffered from defect of wound regeneration. Patients were randomly divided into two groups: patients in the study group (n = 18) were treated with Knutson's formula; patients in the control group (n = 16) were treated with traditional topical drugs. In the study group, 16 of 18 (88.9%) patients reached complete wound closure 1 month after treatment, with no wound infections. In the control group, only three patients (18.7%) showed complete wound closure within a month; in addition, one patient required systemic antibiotic treatment because of supra-bacterial infection of the wound. In our sample, the combination of povidone-iodine and sugar had a higher success rate compared with traditional topical treatment in the treatment of wound defect closure in oncological patients who underwent radio-chemotherapy., (© 2019 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Objective: To evaluate the ability of oral supplements with immune-stimulating molecules (Sambucus nigra, Zinc, Tyndallized Lactobacillus acidophilus (HA122), Arabinogalactans, vitamin D, vitamin E and vitamin C) to reduce the inflammation of the upper airway tract and improve the outcome of otitis media with effusion (OME) in children., Patients and Methods: Randomized controlled trial. One-hundred ninety-eight children (CI 95%: 12-96 months) were divided into four groups. Group 1 (48 subjects) received 10 ml of oral supplements (OS) with immune-stimulating molecules for three months (20 days consecutively, then 10 days of suspension - the therapeutic scheme was repeated three times); Group 2 (54 children) underwent treatment with 10 ml of OS for 90 consecutive days; Group 3 (48 subjects) received 15 ml of OS for 45 consecutive days; a control group (48 children) underwent the standard treatment for rhinitis and OME. Outcome measures included otoscopy, tympanometry, fibroendoscopy, and the pure tone audiometry (PTA) at T0 (before treatment), T1 (45 days after treatment), and T2 (90 days after treatment)., Results: All children treated with OS showed a reduction of Upper Airway Infection (UAI) episodes and OME compared to the control group independent of the administration method and posology. The three groups treated with OS showed statistically significant differences between T0 and T2 for otoscopy, tympanometry, fibroendoscopy, and PTA. In Group 2, the otoscopy and the tympanometry scores improved at T1. Group 2 and 3 had better PTA results than Group 1., Conclusions: OS with immune-stimulating molecules should be considered as a supporting therapy in children affected by recurrent episodes of UAI associated with OME due to their capacity to improve the immune response and reduce the inflammatory phenomena. OS can improve the fibroendoscopic findings by restoring middle ear ventilation, in addition to their ability to reduce inflammation in the middle ear.

Transplantation of hematopoietic cells from a healthy individual (allogeneic hematopoietic cell transplantation (allo-HCT)) demonstrates that adoptive immunotherapy can cure blood cancers: still, post-transplantation relapses remain frequent. To explain their drivers, we analyzed the genomic and gene expression profiles of acute myeloid leukemia (AML) blasts purified from patients at serial time-points during their disease history. We identified a transcriptional signature specific for post-transplantation relapses and highly enriched in immune-related processes, including T cell costimulation and antigen presentation. In two independent patient cohorts we confirmed the deregulation of multiple costimulatory ligands on AML blasts at post-transplantation relapse (PD-L1, B7-H3, CD80, PVRL2), mirrored by concomitant changes in circulating donor T cells. Likewise, we documented the frequent loss of surface expression of HLA-DR, -DQ and -DP on leukemia cells, due to downregulation of the HLA class II regulator CIITA. We show that loss of HLA class II expression and upregulation of inhibitory checkpoint molecules represent alternative modalities to abolish AML recognition from donor-derived T cells, and can be counteracted by interferon-γ or checkpoint blockade, respectively. Our results demonstrate that the deregulation of pathways involved in T cell-mediated allorecognition is a distinctive feature and driver of AML relapses after allo-HCT, which can be rapidly translated into personalized therapies.

The major cause of death after allogeneic Hematopoietic Stem Cell Transplantation (HSCT) for acute myeloid leukemia (AML) is disease relapse. We investigated the expression of Inhibitory Receptors (IR; PD-1/CTLA-4/TIM-3/LAG-3/2B4/KLRG1/GITR) on T cells infiltrating the bone marrow (BM) of 32 AML patients relapsing (median 251 days) or maintaining complete remission (CR; median 1 year) after HSCT. A higher proportion of early-differentiated Memory Stem (T SCM ) and Central Memory BM-T cells express multiple IR in relapsing patients than in CR patients. Exhausted BM-T cells at relapse display a restricted TCR repertoire, impaired effector functions and leukemia-reactive specificities. In 57 patients, early detection of severely exhausted (PD-1 + Eomes + T-bet - ) BM-T SCM predicts relapse. Accordingly, leukemia-specific T cells in patients prone to relapse display exhaustion markers, absent in patients maintaining long-term CR. These results highlight a wide, though reversible, immunological dysfunction in the BM of AML patients relapsing after HSCT and suggest new therapeutic opportunities for the disease.