Metastases to the parotid glands: An institutional experience.

BACKGROUND: Metastatic lesions to the salivary gland are rare and mostly affect the parotids. Metastases represent 8% of all malignant lesions of the parotid gland. Around 80% originate from squamous cell carcinomas (SCC) of the head and neck region. Fine needle aspiration (FNA) plays a crucial role in distinguishing primary salivary gland lesions from metastases. Herein we describe our series of metastases to the parotid glands. MATERIALS AND METHODS: We analysed 630 parotid gland FNAs over a decade including conventional and liquid-based cytology specimens. Ancillary techniques such as immunocytochemistry (ICC) were conducted on cell blocks. RESULTS: Eighty (12.4%) cases were malignant lesions, of which 53 (63.75%) were metastases including 24% melanoma, 22.6% SCC, 19% renal carcinomas, 7.5% breast carcinomas, 11.3% lung, 9% intestinal and 1.8% testicular, malignant solitary fibrous tumour and Merkel cell carcinoma. The 53 cases, classified according to the Milan system for salivary cytopathology, belonged to 5 Suspicious for malignancy (SFM) and 48 malignant (M) categories. Forty had a known history of primary malignancy (75.4%), while 13 were suspicious to be a metastatic localisation (24.5%), distributed as 5SFM (2SCC and 3Melanoma) and 8 M. A combination of clinical history, cytomorphology and ICC identified 100% of them. CONCLUSIONS: Fine needle aspiration plays a central role in the diagnostic workup of patients with metastatic lesions to their parotid glands, thereby defining the correct management. Diagnostic accuracy may be enhanced by applying ICC. Although melanoma and SCC are the most common histological types, several other malignancies may also metastasize to the parotid glands and should be kept into consideration.

Risk of cataract in health care workers exposed to ionizing radiation: a systematic review.

BACKGROUND: The eye is an important sensory organ occupationally exposed to ionizing radiation (IR) in healthcare workers (HCWs) engaged in medical imaging (MI). New evidence highlights the possible induction of cataract at IR exposure levels to be much lower than expected in the past. OBJECTIVE: Conduct an updated review on the current evidence on cataract risk in healthcare workers exposed to IR. METHODS: Published scientific studies on cataract risk in IR exposed healthcare workers were collected through a systematic search of two biomedical databases (MEDLINE and Scopus). Data from included studies was extracted and summarized. Study quality was also assessed. RESULTS: All 21 eligible studies reported an increased prevalence of cataract, especially posterior subcapsular cataract, in IR exposed  HCWs with a higher prevalence in interventional cardiology staff. DISCUSSION: Our review synthesizes the latest evidence to support the hypothesis of a significantly increased risk of occupational cataract in healthcare workers operating MI and exposed to IR, especially in interventional cardiologists. Data also support a dose-response relationship between IR exposure and the prevalence of opacities, especially posterior subcapsular opacities. CONCLUSIONS: Findings highlight the need for effective control measures including appropriate training, adherence to protective procedures, and a constant use of shields and eye personal protective equipment in healthcare workers with optical exposure to IR. Periodic health surveillance programs, possibly including lens evaluation, are also important to monitor cataract risk in these MI operators.

Associated Pulmonary Hypertension Is an Independent Contributor to Exercise Intolerance in Chronic Fibrosing Interstitial Pneumonias.

BACKGROUND: Associated pulmonary hypertension (APH) is frequently observed in fibrosing interstitial pneumonias (FIP), such as idiopathic pulmonary fibrosis (IPF). APH is associated with worse prognosis, but it remains unclear whether it is associated with greater functional impairment. Six-minute walk distance (6MWD) is widely used to assess functional capacity in pulmonary hypertension and FIP. OBJECTIVES: To investigate if APH independently contributes to exercise intolerance in FIP, irrespective of the extent of underlying fibrosis. METHODS: Patients diagnosed with FIP (September 2009 to June 2017) were included in the study if they underwent right heart catheterization, high-resolution chest computed tomography (HRCT), and 6MWD within 3 months. Recruitment was not limited only to patients undergoing lung transplant assessment. APH was defined as mean pulmonary artery pressure (mPAP) ≥25 mm Hg. The extent of fibrosis was quantified on HRCT using a visual fibrosis score by 2 separate observers. RESULTS: Seventy-two patients (60 with IPF) were identified. Fifty-five patients had APH. mPAP was not significantly different in subgroups stratified according to the extent of fibrosis on HRCT. Pulmonary vascular resistance (PVR) was the strongest predictor of 6MWD on both univariate and stepwise regression analyses, and remained so considering only patients with normal wedge pressure (< 15 mm Hg) (n = 61). HRCT fibrosis score and pulmonary function tests did not significantly correlate with 6MWD. CONCLUSIONS: In patients with FIP, PVR is a significant contributor of 6MWD, independently from the extent of fibrosis on HRCT. These results strengthen both the rationale to use 6MWD as endpoint in FIP and to target APH with specific therapies.

Posterior Reversible Encephalopathy Syndrome after Hematopoietic Cell Transplantation in Children with Hemoglobinopathies.

Posterior reversible encephalopathy syndrome (PRES) is a serious adverse event associated with calcineurin inhibitors used for graft-versus-host disease (GVHD) prophylaxis. We compared the incidence of PRES in children with thalassemia (n = 222, 1.4 to 17.8 years old) versus sickle cell disease (SCD; n = 59, 2 to 17 years old) who underwent hematopoietic cell transplantation from HLA-matched siblings or alternative donors and analyzed the risk factors for PRES. Overall, 31 children developed calcineurin inhibitor-related PRES (11%), including 30 patients with seizures and 1 patient without seizures. PRES incidence was significantly higher in SCD patients (22%; 95% confidence interval [CI], 10% to 32%) than in thalassemia patients (8%; 95% CI, 5% to 12%;P = .002). In multivariate analysis, factors associated with PRES were hypertension (hazard ratio [HR], 5.87; 95% CI, 2.57 to 13.43; P = .0001), SCD (HR, 2.49; 95% CI, 1.25 to 4.99; P = .009), and acute GVHD (HR 2.27; 95% CI, 1.06 to 4.85; P= .031). In the entire cohort overall survival (OS) was significantly higher in patients without versus with PRES (90% versus 77%; P = .02). In a subgroup analysis that including matched sibling transplants, OS and disease-free survival (DFS) were similar in thalassemia patients without PRES (92% and 88%, respectively) and with PRES (82% and 73%, respectively), whereas SCD patients with PRES had significantly lower OS (67%) and DFS (67%) than patients without PRES (94% and 94%, respectively; P = .008). Thus, SCD patients had a significantly higher incidence of PRES than thalassemia patients, and hypertension and GVHD were the 2 main risk factors for PRES in patients with hemoglobinopathies. Although PRES did not significantly influence survival in patients with thalassemia, patients with SCD had significantly lower survival after PRES.

NEPA, a fixed oral combination of netupitant and palonosetron, improves control of chemotherapy-induced nausea and vomiting (CINV) over multiple cycles of chemotherapy: results of a randomized, double-blind, phase 3 trial versus oral palonosetron.

PURPOSE: Antiemetic guidelines recommend co-administration of targeted prophylactic medications inhibiting molecular pathways involved in emesis. NEPA is a fixed oral combination of a new NK1 receptor antagonist (RA), netupitant (NETU 300 mg), and palonosetron (PALO 0.50 mg), a pharmacologically distinct 5-HT3 RA. NEPA showed superior prevention of chemotherapy-induced nausea and vomiting (CINV) compared with oral PALO in a single chemotherapy cycle; maintenance of efficacy/safety over continuing cycles is the objective of this study. METHODS: This study is a multinational, double-blind study comparing a single oral dose of NEPA vs oral PALO in chemotherapy-naïve patients receiving anthracycline/cyclophosphamide-based chemotherapy along with dexamethasone 12 mg (NEPA) or 20 mg (PALO) on day 1. The primary efficacy endpoint was delayed (25-120 h) complete response (CR: no emesis, no rescue medication) in cycle 1. Sustained efficacy was evaluated during the multicycle extension by calculating the proportion of patients with overall (0-120 h) CR in cycles 2-4 and by assessing the probability of sustained CR over multiple cycles. RESULTS: Of 1455 patients randomized, 1286 (88 %) participated in the multiple-cycle extension for a total of 5969 cycles; 76 % completed ≥4 cycles. The proportion of patients with an overall CR was significantly greater for NEPA than oral PALO for cycles 1-4 (74.3 vs 66.6 %, 80.3 vs 66.7 %, 83.8 vs 70.3 %, and 83.8 vs 74.6 %, respectively; p ≤ 0.001 each cycle). The cumulative percentage of patients with a sustained CR over all 4 cycles was also greater for NEPA (p < 0.0001). NEPA was well tolerated over cycles. CONCLUSIONS: NEPA, a convenient, guideline-consistent, fixed antiemetic combination is effective and safe over multiple cycles of chemotherapy.

Safety of an Oral Fixed Combination of Netupitant and Palonosetron (NEPA): Pooled Data From the Phase II/III Clinical Program.

BACKGROUND: Standard prophylaxis for chemotherapy-induced nausea and vomiting (CINV) with highly emetogenic and anthracycline-cyclophosphamide-based chemotherapy includes a 5-hydroxytryptamine-3 receptor antagonist, a neurokinin-1 receptor antagonist (NK1RA), and corticosteroid therapy. NEPA is a fixed combination of netupitant and palonosetron. The primary objective of this analysis was to document the safety profile, including cardiac safety, of NEPA + dexamethasone in comparison with current therapies across all phase II/III trials. MATERIALS AND METHODS: This pooled analysis was based on data from 3,280 patients in 4 randomized, double-blind clinical trials. Patients were categorized into 1 of 3 pooled groups on the basis of actual treatment received: NEPA + dexamethasone, palonosetron + dexamethasone, and aprepitant + ondansetron/palonosetron + dexamethasone. Safety was assessed by number and frequency of adverse events (AEs) and changes from baseline electrocardiogram measures. RESULTS: Most patients were female and younger than 65 years of age. Demographic characteristics varied among studies and pooled groups. Frequencies of treatment-emergent AEs (TEAEs) and treatment-related AEs (TRAEs) were similar across groups. TEAEs were mostly mild and consistent with expected chemotherapy and disease-related AEs (hematologic events, hair loss, general weakness). TRAEs in ≥2% of patients were headache and constipation. Frequencies of cardiac TEAEs were similar across groups, with QT prolongation (1.6%), tachycardia (1.1%), and dyspnea (0.9%) the most common. Serious cardiac TEAEs were rare. CONCLUSION: NEPA was well-tolerated, with an AE profile as expected for the regimen. Sample size, demographic characteristics, study design, chemotherapy, and antiemetic regimen differences across the four studies may have contributed to differences in frequencies of neutropenia and alopecia. Adding an NK1RA to a CINV prophylaxis regimen can improve outcomes without additional toxicity. IMPLICATIONS FOR PRACTICE: Supportive care for cancer should ideally be efficacious, convenient, and well-tolerated. There have been concerns about cardiac safety with current antiemetic prophylactic agents, namely dolasetron and ondansetron. This pooled safety analysis demonstrates that the new oral fixed combination therapy NEPA can be safely added to an antiemetic regimen without increased toxicity.

Drug-drug interaction profile of components of a fixed combination of netupitant and palonosetron: Review of clinical data.

Neurokinin-1 (NK1) receptor antagonists (RAs) are commonly coadministered with serotonin (5-HT3) RAs (e.g. palonosetron (PALO)) to prevent chemotherapy-induced nausea/vomiting. Netupitant/palonosetron (NEPA), an oral fixed combination of netupitant (NETU)-a new NK1 RA-and PALO, is currently under development. In vitro data suggest that NETU inhibits CYP3A4 and is a substrate for and weak inhibitor of P-glycoprotein (P-gp). This review evaluates potential drug-drug interactions between NETU or NEPA and CYP3A4 substrates/inducers/inhibitors or P-gp substrates in healthy subjects. Pharmacokinetic (PK) parameters were evaluated for each drug when NETU was coadministered with PALO (single doses) and when single doses of NETU or NEPA were coadministered with CYP3A4 substrates (erythromycin (ERY), midazolam (MID), dexamethasone (DEX), or oral contraceptives), inhibitors (ketoconazole (KETO)), or inducers (rifampicin (RIF)), or a P-gp substrate (digoxin (DIG)). Results showed no relevant PK interactions between NETU and PALO. Coadministration of NETU increased MID and ERY exposure and significantly increased DEX exposure in a dose-dependent manner; NETU exposure was unaffected. NEPA coadministration had no clinically significant effect on oral contraception, although levonorgestrel exposure increased. NETU exposure increased after coadministration of NEPA with KETO and decreased after coadministration with RIF; PALO exposure was unaffected. NETU coadministration did not influence DIG exposure. In conclusion, there were no clinically relevant interactions between NETU and PALO, or NEPA and oral contraceptives (based on levonorgestrel and ethinylestradiol exposure). Coadministration of NETU or NEPA with CYP3A4 inducers/inhibitors/substrates should be done with caution. Dose reduction is recommended for DEX. Dose adjustments are not needed for NETU coadministration with P-gp substrates.

Efficacy and safety of oral palonosetron compared with IV palonosetron administered with dexamethasone for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients with solid tumors receiving cisplatin-based highly emetogenic chemotherapy (HEC).

PURPOSE: This study aims to compare the efficacy and safety of oral palonosetron with intravenous (IV) palonosetron for the prevention of cisplatin-related chemotherapy-induced nausea and vomiting (CINV). METHODS: A multinational, randomized, double-blind study enrolling adult chemotherapy-naive patients with malignant solid tumors scheduled to receive cisplatin-based highly emetogenic chemotherapy (HEC). Patients received oral palonosetron (0.50 mg) or IV palonosetron (0.25 mg), each with oral dexamethasone. The primary objective was to demonstrate non-inferiority in terms of patients with a complete response (CR, no emesis/no rescue medication) within the acute phase (0-24 h after chemotherapy administration). RESULTS: Of the 743 patients randomized, 739 received study medications and 738 were included in the full analysis set. The CR rate in the acute phase was high for both groups (oral 89.4 %; IV 86.2 %). As this difference in proportions (stratum-adjusted Cochran-Mantel-Haenszel method) was 3.21 % (99 % confidence interval (CI) -2.74 to 9.17 %), non-inferiority was demonstrated (since the lower limit of the 99 % CI was closer to zero than the predefined margin of 15 %). Treatment-emergent adverse events (TEAEs) related to the study drug were rare (oral 3.2 %; IV 6.5 %). No TEAEs related to study drug leading to discontinuation were reported. CONCLUSION: Non-inferiority of oral versus IV palonosetron was demonstrated. The CR rate in the acute phase was >86 % in both patient groups. The safety profiles were comparable.

Hybrid primary puncture in stapler-assisted total laryngectomy.

In Video S1, a new surgical technique for hybrid primary tracheoesophageal (TE) puncture in stapler-assisted total laryngectomy is shown. The video describes the surgical steps of the procedure and illustrates some tips and tricks. The procedure incorporates an upper mini-pharyngotomy to enable retrograde placement of the voice prosthesis (VP), eliminating the need for rigid esophagoscopy. This has made it possible to exploit, without additional risks, the potential of the stapler combined with primary TE puncture and VP placement. In our experience, this hybrid procedure in stapler-assisted total laryngectomy is not related to adverse events such as pharyngocutaneous fistula (PCF), hypertonicity, and functional complications. Therefore, it can be considered a valid technique that allows for easy insertion of a primary voice prosthesis also in case of mechanical sutures.

p16 Expression in Laryngeal Squamous Cell Carcinoma: A Surrogate or Independent Prognostic Marker?

Laryngeal squamous cell carcinoma (LSCC) is a common malignancy that, despite scientific advancements, has not seen an improvement in its prognosis in the last decades. Few promising predictive markers have been found and none are relevant in clinical practice. p16ink4a, an oncosuppressor protein involved in cell cycle arrest, with a prognostic impact on other cancers, has been widely used in the head and neck region as a surrogate marker of HPV infection. Published papers and recent meta-analyses seem to minimize the biological role of HPV in the context of LSCC's cancerogenesis, and to disprove the reliability of p16ink4a as a surrogate prognostic marker in this context, while still highlighting its potential role as an independent predictor of survival. Unfortunately, the available literature, in particular during the last two decades, is often not focused on its potential role as an independent biomarker and few relevant data are found in papers mainly focused on HPV. The available data suggest that future research should focus specifically on p16ink4a, taking into account both its potential inactivation and overexpression, different patterns of staining, and immunohistochemistry cutoffs, and should focus not on its potential role as a surrogate marker but on its independent role as a predictor of survival.

Effect of netupitant, a highly selective NK1 receptor antagonist, on the pharmacokinetics of midazolam, erythromycin, and dexamethasone.

PURPOSE: Netupitant is a new highly selective neurokinin-1 receptor antagonist being studied for the prevention of nausea and vomiting in patients undergoing chemotherapy. In vitro studies suggest that netupitant inhibits the cytochrome P-450 isoenzyme 3A4 (CYP3A4). Because netupitant may be used with a variety of drugs, which may be substrates of CYP3A4, two studies were designed to establish the potential risk for drug-drug interaction with three different CYP3A4 substrates: midazolam, erythromycin, and dexamethasone. METHODS: Both trials were three-period crossover studies performed in healthy subjects. In the first study, 20 subjects received netupitant and either midazolam or erythromycin. In the second study, 25 subjects received netupitant and dexamethasone. Serial blood samples were collected over the course of the two studies and pharmacokinetic parameters were determined for all analytes. RESULTS: Netupitant, by inhibiting the CYP3A4, increased the C max and AUCinf of midazolam by 40 and 144 %, respectively, and the C max and AUCinf of erythromycin by 30 %. Netupitant was shown to increase the exposure to dexamethasone in a dose-dependent manner with the mean increase in AUC and C max by 72 and 11 %, respectively, on day 1 and by 138 and 75 %, respectively, on day 4 when co-administered with 300 mg of netupitant. CONCLUSIONS: The results of these studies suggest that netupitant is a moderate inhibitor of CYP3A4 and therefore, co-administration with drugs that are substrates of CYP3A4 may require dose adjustments. Treatments were well tolerated in both studies.

Effect of netupitant, a highly selective NK1 receptor antagonist, on the pharmacokinetics of palonosetron and impact of the fixed dose combination of netupitant and palonosetron when coadministered with ketoconazole, rifampicin, and oral contraceptives.

OBJECTIVES: Neurokinin-1 receptor antagonists (NK1 RAs) are commonly coadministered with a 5-HT3 RA such as palonosetron to prevent nausea and vomiting induced by chemotherapy. Netupitant, a new highly selective NK1 RA, is both a substrate for and a moderate inhibitor of CYP3A4. Three studies were designed to evaluate the potential drug-drug interaction of netupitant with palonosetron and of the fixed dose combination of netupitant and palonosetron, NEPA, with an inhibitor (ketoconazole), an inducer (rifampicin) and a substrate (oral contraceptives) of CYP3A4. METHODS: Study 1 was a three-way crossover in 18 healthy subjects receiving netupitant alone, palonosetron alone, and the combination of both antiemetics. Studies 2 and 3 were two-way crossover trials where healthy subjects received NEPA (the fixed dose combination of netupitant and palonosetron). In study 2, 36 subjects received NEPA alone (day 1) and in combination with ketoconazole or rifampicin. In study 3, 24 healthy women received ethinylestradiol/levonorgestrel alone or in combination with NEPA (day 1). RESULTS: There were no significant pharmacokinetic interactions between netupitant and palonosetron. Ketoconazole increased netupitant area under curve (AUC) by 140 % and C max by 25 %. Rifampicin decreased netupitant AUC by 83 % and C max by 62 %. NEPA did not significantly affect exposure to ethinylestradiol, while systemic exposure to levonorgestrel increased by 40 %, but this was not considered clinically relevant. CONCLUSIONS: There were no clinically relevant interactions between netupitant and palonosetron, or between NEPA and oral contraceptives. The coadministration of NEPA with inhibitors or inducers of CYP3A4 may require dose adjustments. Treatments were well tolerated.

Validity of Italian adaptation of the Vanderbilt Paediatric Dizziness Handicap Inventory.

Objective: The paediatric caregiver version of the Dizziness Handicap Inventory (DHI-PC) questionnaire is a useful Quality of Life (QoL) evaluation instrument for children experiencing dizziness, vertigo or unsteadiness. Its English version has been validated for use with a paediatric population between 5 and 12 years of age. The aim of this work is to validate the DHI-PC into Italian for both patient assessment and appropriate rehabilitative treatment planning. Materials and methods: Cross-cultural adaptation of the DHI-PC was performed using standard techniques. Items of the original questionnaire were translated into Italian by two bilingual investigators. Two native English speakers carried out a back translation of the new version that was compared with the original to check that they had the same semantic value. A pre-final version was obtained by an expert committee and was applied in a pilot test. Results: A total of 42 patient caregivers completed the final adapted questionnaire twice with an interval of 2 weeks. Internal consistency was excellent, with Cronbach's alpha = 0.95. Conclusions: Our study showed evidence that the Italian version of DHI-PC is a valid and reliable tool to quantify the degree of dizziness handicap and its application is recommended.

Impact of lymph node ratio and number of lymph node metastases on survival and recurrence in laryngeal squamous cell carcinoma.

INTRODUCTION: The aim of this study is to assess the impact of lymph node ratio (LNR) and number of positive lymph nodes (NPLN) on mortality and recurrence rates in patients with laryngeal squamous cell carcinoma. MATERIALS AND METHODS: We conducted a retrospective multicenter international study involving 24 Otorhinolaryngology-Head and Neck Surgery divisions. Disease-specific survival (DSS) and disease-free survival (DFS) were evaluated as the main outcomes. The curves for DSS and DFS according to NPLN and LNR were analyzed to identify significant variations and establish specific cut-off values. RESULTS: 2507 patients met the inclusion criteria. DSS and DFS were significantly different in the groups of patients stratified according to LNR and NPLN. The 5-year DSS and DFS based on LNR and NPLN demonstrated an improved ability to stratify patients when compared to pN staging. CONCLUSION: Our data demonstrate the potential prognostic value of NPLN and LNR in laryngeal squamous cell carcinoma.

Thinking biases and their role in persecutory delusions: A systematic review.

AIM: Thinking biases are posited to be involved in the genesis and maintenance of delusions. Persecutory delusions are one of the most commonly occurring delusional subtypes and cause substantial distress and disability to the individuals experiencing them. Their clinical relevance confers a rationale for investigating them. Particularly, this review aims to elucidate which cognitive biases are involved in their development and persistence. METHODS: MEDLINE, Embase, PsycINFO and Global Health were searched from the year 2000 to June 2020. A formal narrative synthesis was employed to report the findings and a quality assessment of included studies was conducted. RESULTS: Twenty five studies were included. Overall, 18 thinking biases were identified. Hostility and trustworthiness judgement biases appeared to be specific to persecutory delusions while jumping to conclusions, self-serving attributional biases and belief inflexibility were proposed to be more closely related to other delusional subtypes. While the majority of the biases identified were suggested to be involved in delusion maintenance, hostility biases, need for closure and personalizing attributional biases were believed to also have aetiological influences. CONCLUSIONS: These findings show that some cognitive biases are specific to paranoid psychosis and appear to be involved in the formation and/or persistence of persecutory delusions.

Italian Validation of the Sexual Desire Inventory (SDI-2): Psychometric Properties and Factorial Structure.

OBJECTIVE: Sexual desire is a psychological state that prompts individuals to engage in sexual activity. Although interest about this topic is constantly increasing, there are no validated instruments to measure sexual desire in Italy, making scientific studies difficult. This paper aims to provide a contribution to validation of the Sexual Desire Inventory-2 (SDI-2) for the Italian population, investigating factorial structure, invariance, reliability and validity. METHOD: The sample was composed of 389 Italian participants from a nonclinical population. The thirteen-item SDI-2 and the Barratt Impulsiveness Scale (BIS-11) for measuring impulsiveness were administered. RESULTS: The results supported two dimensions, i.e. dyadic and solitary desire, and partially measurement invariance across gender. Furthermore, good validity and reliability indicators have been gained. CONCLUSIONS: the Italian version of the SDI-2 supports good psychometrics properties. It may be considered a valid and reliable measure for assessing dyadic and solitary sexual desire. Therefore, the present inventory may be used, in the research and clinical field, as an innovative instrument in order to investigate sexual desire and its relationship with clinical disorders.

Benefit of cochlear implantation in a patient with Myhre syndrome.

Myhre syndrome is a rare disorder characterised by short stature, skeletal anomalies, facial dysmorphism and hearing loss (HL), resulting from heterozygous mutations of the SMAD4 gene. We describe the benefits of cochlear implant (CI) in a patient with sensorineural HL carrying a mutation (NM_005359.6: c.1498A>G; p.lle500Val) within the SMAD4 gene, detected by whole-exome sequencing. The CI was inserted through the round window despite otospongiotic abnormalities. Pure-tone audiometry improved up to 20 dBHL. Speech perception in noise (Simplified Noise Reduction - SNR +10) increased from 0% pre implantation with hearing aids to 50% post implantation. The postoperative setting of the electrical stimulation limits yielded an asymmetric map, with lower levels for central electrodes and higher levels for lateral ones. Action potential could not be evoked via medial electrodes, suggesting a cochlear nerve dysfunction. Outcomes related to quality of life and cognitive impairment improved. CI was shown to be an effective auditory rehabilitation strategy.

The evaluation of global cognitive and emotional status of older patients with chronic tinnitus.

OBJECTIVES: Tinnitus is a common symptom largely impactful on quality of life, especially in the elderly. Our aim was to evaluate the efficacy of self-administered screening tests to correlate the severity of subjective perception of tinnitus with emotional disorders and the overall cognitive status. METHODS: Patients aged ≥ 55 years with chronic tinnitus were recruited and submitted to a complete audiological evaluation; Tinnitus Handicap inventory (THI); Hospital Anxiety and Depression Scale (HADS-A and HADS-D) and Mini-Mental State Examination (MMSE). Demographic and audiological features of patients with and without cognitive impairment (MMSE score cut-off of 24/30) were analyzed in order to reveal the relationship among tinnitus, emotional disorders, and cognitive dysfunction. RESULTS: 102 patients were recruited (mean age: 70.4 ± 9.6). THI score was directly related to HADS-A score (r = .63) HADS-D score (r = .66), whereas there was no relationship between tinnitus severity and MMSE (r = .13). CI and n-CI groups did not differ in the characteristics of tinnitus (p > .05), however, hearing threshold (p = .049) and anxious depressive traits measured with HADS-A (p = .044) and HADS-D (p = .016) were significantly higher in the group with cognitive impairment. Furthermore, age ≥ 75 years (p = .002, OR = 13.8), female sex (p = .032; OR = 6.5), severe hearing loss (p = .036; OR = 2.3), and anxiety (p = .029; OR = 9.2) resulted risk factors for CI. Therefore, in CI group MMSE score was inversely related to age (r = -.84). CONCLUSIONS: Cognitive impairment and psychiatric discomfort should be considered in tinnitus patients, related to increasing age, female sex, and severe hearing loss. Thus, self-administered questionnaires can be useful in addressing clinical approach.

Factors Associated with SARS-CoV-2 Infection Risk among Healthcare Workers of an Italian University Hospital.

We report the results of a study on the cumulative incidence of SARS-CoV-2 infections in about 6000 workers of the University Hospital of Modena, Northern Italy, in the period March 2020-January 2021, and the relations with some individual and occupational factors. Overall, in healthcare workers (HCW) the cumulative incidence of COVID-19 during the period was 13.8%. Results confirm the role of overweight and obesity as significant risk factors for SARS-CoV-2 infection. Chronic respiratory diseases, including asthma, also proved to be significantly associated with the infection rate. Considering occupational factors, the COVID-19 risk was about threefold (OR: 2.7; 95% CI 1.7-4.5) greater in nurses and nurse aides than in non-HCW, and about double (OR: 1.9; 95% CI 1.2-3.2) in physicians. Interestingly, an association was also observed between infection risk and nightshifts at work (OR: 1.8; 95% CI 1.4-2.3), significantly related to the total number of shifts in the whole eleven-month period. Even if the vaccination campaign has now greatly modified the scenario of SARS-CoV-2 infections among HCW, the results of this study can be useful for further development of health and policy strategies to mitigate the occupational risk related to the new variants of coronavirus, and therefore the evolution of the pandemic.

Effect of HXT1 and HXT7 hexose transporter overexpression on wild-type and lactic acid producing Saccharomyces cerevisiae cells.

BACKGROUND: Since about three decades, Saccharomyces cerevisiae can be engineered to efficiently produce proteins and metabolites. Even recognizing that in baker's yeast one determining step for the glucose consumption rate is the sugar uptake, this fact has never been conceived to improve the metabolite(s) productivity.In this work we compared the ethanol and/or the lactic acid production from wild type and metabolically engineered S. cerevisiae cells expressing an additional copy of one hexose transporter. RESULTS: Different S. cerevisiae strains (wild type and metabolically engineered for lactic acid production) were transformed with the HXT1 or the HXT7 gene encoding for hexose transporters.Data obtained suggest that the overexpression of an Hxt transporter may lead to an increase in glucose uptake that could result in an increased ethanol and/or lactic acid productivities. As a consequence of the increased productivity and of the reduced process timing, a higher production was measured. CONCLUSION: Metabolic pathway manipulation for improving the properties and the productivity of microorganisms is a well established concept. A high production relies on a multi-factorial system. We showed that by modulating the first step of the pathway leading to lactic acid accumulation an improvement of about 15% in lactic acid production can be obtained in a yeast strain already developed for industrial application.