Recovery of Smell and Taste in Patients With Persistent COVID-19-Related Hyposmia and Dysgeusia by Targeting Inflammation and Endothelial Dysfunction.

Purpose New-onset loss of olfaction and/or taste is now recognized among the hallmark symptoms of COVID-19. In most patients, these symptoms resolve completely and spontaneously within days. However, some patients experience persistent olfactory and gustatory dysfunction after COVID-19 resolution. We evaluated the efficacy of a treatment combining several therapeutic agents to target inflammation and endothelial dysfunction in patients with persistent hyposmia and dysgeusia. Methods This 12-month observational pilot study involved patients presenting with symptoms of hyposmia and dysgeusia 30 days after COVID-19 had subsided. The main objective was to evaluate the efficacy of a combination of systemic corticosteroids, a glycosaminoglycan (GAG)-based antithrombotic (mesoglycan), a diuretic, and a vitamin complex. The perceived extent of olfaction and taste impairment was assessed using an 11-point visual analog scale (VAS), where 0 = complete loss of olfaction/taste and 10 = complete recovery of olfaction/taste. Results Eighty-seven patients with post-COVID-19 hyposmia and dysgeusia were enrolled. At treatment start (T0), the mean VAS scores were 2.0 and 3.2 for olfactory and gustatory functions, respectively. Both functions appeared to improve progressively and significantly from T0 to 12 months. A shorter time between viral infection and the start of treatment was associated with a more pronounced recovery of both senses. Conclusions Combined systemic corticosteroid, GAG-based antithrombotic agent (mesoglycan), and diuretic may constitute an option for treating persistent hyposmia and dysgeusia associated with COVID-19. To ensure optimal recovery, early treatment start is recommended. The described treatment protocol deserves to be further evaluated.

Mini-invasive video-assisted thyroidectomy vs robot-assisted transaxillary thryoidectomy: analisys and comparison of safety and outcomes.

Thyroid surgery is characterized by large volumes and typically affects a young female population. Mini-invasive or remote access surgical techniques are born driven by the desire to improve aesthetic outcomes of the traditional technique, following technological advances that have upset the surgical world in the last 20 years. In our multicenter, retrospective observational study, we first compared an endoscopic technique with a robotic one: minimally invasive video-assisted thyroidectomy (MIVAT) and robot-assisted transaxillary thyroidectomy (RATT). We evaluated intraoperative features, complications, and cosmetic outcomes in a cohort of 609 patients. The efficacy and safety of these techniques are proven by a large literature and the comparison made in our study does not show inferiority of one technique compared to the other. Even the aesthetic results tend to be equal in the long term. It is desirable that further prospective and randomized studies are conducted to evaluate the outcomes of these procedures and the cost-benefit ratio.

How can sleep disorders affect our reaction towards external stressors: a lesson from the COVID-19 outbreak.

BACKGROUND: The COVID-19 outbreak produced extensive psychological consequences, especially among vulnerable populations. Sleep was identified as one of the most common "indirect targets" of the pandemia, with up to 74.8% of patients surviving from COVID-19 complaining of new-onset sleep disorders. However, so far, the clinic-psychological impact of the outbreak in patients affected by pre-existing sleep disorders has not been examined in details. MATERIALS AND METHODS: In the present study, we aim to assess the effect of the COVID-19 outbreak in a cohort of 190 adult patients affected by sleep disorders, compared to 265 age and sex-matched healthy sleepers. The assessment was implemented throughout the use of ad hoc anamnestic questions, exploration of dream content, and validated questionnaires, aiming to capture the broad range of the neuropsychological nuances of the COVID-19 impact. RESULTS: Subjects with pre-existent sleep disorders faced a more severe impact in terms of sleep quality and amount compared to healthy sleepers, presenting longer sleep latency, reduced sleep efficacy, and greater use of hypnotics and medications. On the other hand, healthy sleepers experienced deeper variation in sleeping habits, sleep duration, and greater impact on dream activity in terms of content, emotionality, and presence of recurrent dreams. Finally, in our sample, being female represents an important aggravating factor in the pandemic experience, both in terms of sleep deterioration and with respect to physical and mental health. For instance, females indeed presented the highest scores of Pittsburgh Sleep Quality Index (PSQI) both in cases and control groups (respectively 10 ± 3.8 vs 7.3 ± 3.9 in cases and 6.6 ± 3.6 vs 6.0 ± 3.4 in controls, p-value < 0.001). CONCLUSION: Pre-existent sleep disorders and the female sex might represent risk factors increasing the clinic-psychological burden in dramatic scenarios, such as the COVID-19 pandemia, requiring dedicated attention from clinicians.

High CD49a+ NK cell infiltrate is associated with poor clinical outcomes in Hepatocellular Carcinoma.

NK cells infiltrating Hepatocellular Carcinoma (HCC) may express residency markers such as Integrin Subunit Alpha 1 (CD49a) that have been associated with nurturing functions in the decidua, and characterized by the production of angiogenic factors as well as loss of cytotoxicity. CIBERSORT, a computational analysis method for quantifying cell fractions from bulk tissue gene expression profiles, was used to estimate the infiltrating immune cell composition of the tumor microenvironment from gene expression profiles of a large cohort of 225 HCCs in the public GEO database. Decidual-like CD49a+ NK cells, in addition to another 22 immune cell populations, were characterized and thoroughly investigated so that HCC cell heterogeneity in a large cohort of 225 HCCs from the public GEO database could be studied. An inverse correlation of the expression of CD49a+ NK-cells and CD8+ T-cells suggested a negative association with clinical outcomes. This result was confirmed in a further validation cohort of 100 HCC patients from The Cancer Genome Atlas, Liver Hepatocellular Carcinoma (TCGA-LIHC). Cox regression analysis did not identify CD49a+ cells as a variable independently associated with survival. However, a more abundant infiltrate of this subset was present in patients at a more advanced pathological and clinical HCC stage. In conclusion, we found that NK cells, with a decidual-like gene expression profile, are enriched in HCC, and their abundance increases not only in tumor size but also at advanced stages of the disease suggesting that these cells play a role in tumor growth. For this reason, these NK cells may represent a possible new target for immunotherapeutic approaches in HCC.

Percutaneous Ablation of T1 Renal Masses: Comparative Local Control and Complications after Radiofrequency and Cryoablation.

The efficacy and complication rates of percutaneous radiofrequency ablation (RFA) and cryoablation (CA) in the treatment of T1 renal masses in two Northern Italy hospitals were retrospectively investigated. Eighty-two patients with 80 T1a tumors and 10 T1b tumors treated with thermal ablation from 2015 through 2020 were included. A total of 43 tumors in 38 patients were treated with RFA (2.3 ± 0.9 cm), and 47 tumors in 44 patients were treated with CA (2.1 ± 0.8 cm). The mean follow-up observation period was 26 ± 19 months. The major complications and efficacy, as measured using the technical success and local tumor recurrence rates, were recorded. There were three (6.9%) technical failures with RFA and one (2.1%) with cryoablation (p = 0.30). Among the 40 tumors that were successfully treated with RFA, 1 tumor (2.5%) developed local tumor recurrence; 5/46 tumors that were treated with cryoablation (10.8%) developed local tumor recurrence (p = 0.17). T1b lesions (4.0 ± 0.7 cm) resulted in 1/6 technically unsuccessful cases with RFA and 0/4 with CA. No recurrent disease was detected in the T1b lesions. Major complications occurred after 2.3% (1/43) of RFAs and 0/47 of cryoablation procedures. RFA and cryoablation are both effective in the treatment of renal masses. Major complications with either procedure are uncommon.

ADM-Assisted Direct-to-Implant Prepectoral Breast Reconstruction in Postmastectomy Radiation Therapy Setting: Long-Term Results.

BACKGROUND: Postmastectomy radiotherapy (PMRT) on immediate breast reconstruction historically involved a marked increase in complication rate (up to 50%). Prepectoral breast reconstruction (PPBR) has shown promising early postoperative results. This study aims to evaluate PPBR long-term results in PMRT setting. MATERIALS AND METHODS: This is a retrospective monocentric analysis of 485 PPBR (439 patients) undergoing Acellular-Dermal-Matrix assisted direct-to-implant reconstruction (46 bilateral procedures) between January 2015 and December 2020 (mean FU:35.6 months). Group 1 comprised 401 PPBR not submitted to PMRT, and 84 reconstructions receiving PMRT in Group 2. Patients' characteristics, postoperative complication and revisional surgery rate were examined. PMRT characteristics and subcutaneous tissue thickness, measured in Group 2 by CT scan, were also evaluated. RESULTS: Long-term complication rate was 11.2% in Group 1 vs. 21.4% in Group 2 (P-value = .019). Capsular contracture represented the only complication associated to a statistically significant difference between the 2 groups (P-value < .001). In Group 2, only 4.8% implant loss and 8.3% severe capsular contracture rate was found. In patients who underwent PMRT, 38.9% of complications settled with no consequences, and only 4.8% of patients needed revisional surgery in the long-term FU. According to multivariate analysis, drug intake and PMRT were significantly associated with postoperative complications. In Group 2, a thinner subcutaneous tissue was linked to a higher complication risk. CONCLUSION: In our series, patients treated with PPBR who underwent PMRT, presented a low complication rate and minimal need for revisional surgery in the long-term follow-up, suggesting that this technique is feasible and safe also in PMRT context.

Natural heteroclitic-like peptides are generated by SARS-CoV-2 mutations.

Humoral immunity is sensitive to evasion by SARS-CoV-2 mutants, but CD8 T cells seem to be more resistant to mutational inactivation. By a systematic analysis of 30 spike variant peptides containing the most relevant VOC and VOI mutations that have accumulated overtime, we show that in vaccinated and convalescent subjects, mutated epitopes can have not only a neutral or inhibitory effect on CD8 T cell recognition but can also enhance or generate de novo CD8 T cell responses. The emergence of these mutated T cell function enhancing epitopes likely reflects an epiphenomenon of SARS-CoV-2 evolution driven by antibody evasion and increased virus transmissibility. In a subset of individuals with weak and narrowly focused CD8 T cell responses selection of these heteroclitic-like epitopes may bear clinical relevance by improving antiviral protection. The functional enhancing effect of these peptides is also worth of consideration for the future development of new generation, more potent COVID-19 vaccines.

Deregulated intracellular pathways define novel molecular targets for HBV-specific CD8 T cell reconstitution in chronic hepatitis B.

BACKGROUND & AIMS: In chronic HBV infection, elevated reactive oxygen species levels derived from dysfunctional mitochondria can cause increased protein oxidation and DNA damage in exhausted virus-specific CD8 T cells. The aim of this study was to understand how these defects are mechanistically interconnected to further elucidate T cell exhaustion pathogenesis and, doing so, to devise novel T cell-based therapies. METHODS: DNA damage and repair mechanisms, including parylation, CD38 expression, and telomere length were studied in HBV-specific CD8 T cells from chronic HBV patients. Correction of intracellular signalling alterations and improvement of antiviral T cell functions by the NAD precursor nicotinamide mononucleotide and by CD38 inhibition was assessed. RESULTS: Elevated DNA damage was associated with defective DNA repair processes, including NAD-dependent parylation, in HBV-specific CD8 cells of chronic HBV patients. NAD depletion was indicated by the overexpression of CD38, the major NAD consumer, and by the significant improvement of DNA repair mechanisms, and mitochondrial and proteostasis functions by NAD supplementation, which could also improve the HBV-specific antiviral CD8 T cell function. CONCLUSIONS: Our study delineates a model of CD8 T cell exhaustion whereby multiple interconnected intracellular defects, including telomere shortening, are causally related to NAD depletion suggesting similarities between T cell exhaustion and cell senescence. Correction of these deregulated intracellular functions by NAD supplementation can also restore antiviral CD8 T cell activity and thus represents a promising potential therapeutic strategy for chronic HBV infection. IMPACT AND IMPLICATIONS: Correction of HBV-specific CD8 T cell dysfunction is believed to represent a rational strategy to cure chronic HBV infection, which however requires a deep understanding of HBV immune pathogenesis to identify the most important targets for functional T cell reconstitution strategies. This study identifies a central role played by NAD depletion in the intracellular vicious circle that maintains CD8 T cell exhaustion, showing that its replenishment can correct impaired intracellular mechanisms and reconstitute efficient antiviral CD8 T cell function, with implications for the design of novel immune anti-HBV therapies. As these intracellular defects are likely shared with other chronic virus infections where CD8 exhaustion can affect virus clearance, these results can likely also be of pathogenetic relevance for other infection models.

Notch-Jagged1 signaling and response to bevacizumab therapy in advanced colorectal cancer: A glance to radiomics or back to physiopathology?

Introduction: The Notch intracellular domain (NICD) and its ligands Jagged-1(Jag1), Delta-like ligand (DLL-3) and DLL4 play an important role in neoangiogenesis. Previous studies suggest a correlation between the tissue levels of NICD and response to therapy with bevacizumab in colorectal cancer (CRC). Another marker that may predict outcome in CRC is radiomics of liver metastases. The aim of this study was to investigate the expression of NICD and its ligands and the role of radiomics in the selection of treatment-naive metastatic CRC patients receiving bevacizumab. Methods: Immunohistochemistry (IHC) for NICD, Jag1 and E-cadherin was performed on the tissue microarrays (TMAs) of 111 patients with metastatic CRC treated with bevacizumab and chemotherapy. Both the intensity and the percentage of stained cells were evaluated. The absolute number of CD4+ and CD8+ lymphocytes was counted in three different high-power fields and the mean values obtained were used to determine the CD4/CD8 ratio. The positivity of tumor cells to DLL3 and DLL4 was studied. The microvascular density (MVD) was assessed in fifteen cases by counting the microvessels at 20x magnification and expressed as MVD score. Abdominal CT scans were retrieved and imported into a dedicated workstation for radiomic analysis. Manually drawn regions of interest (ROI) allowed the extraction of radiomic features (RFs) from the tumor. Results: A positive association was found between NICD and Jag1 expression (p < 0.001). Median PFS was significantly shorter in patients whose tumors expressed high NICD and Jag1 (6.43 months vs 11.53 months for negative cases; p = 0.001). Those with an MVD score ≥5 (CD31-high, NICD/Jag1 positive) experienced significantly poorer survival. The radiomic model developed to predict short and long-term survival and PFS yielded a ROC-AUC of 0.709; when integrated with clinical and histopathological data, the integrated model improved the predictive score (ROC-AUC of 0.823). Discussion: These results show that high NICD and Jag1 expression are associated with progressive disease and early disease progression to anti VEGF-based therapy; the preliminary radiomic analyses show that the integration of quantitative information with clinical and histological data display the highest performance in predicting the outcome of CRC patients.

Phenotypic CD8 T cell profiling in chronic hepatitis B to predict HBV-specific CD8 T cell susceptibility to functional restoration in vitro.

OBJECTIVE: Exhausted hepatitis B virus (HBV)-specific CD8 T cells in chronic HBV infection are broadly heterogeneous. Characterisation of their functional impairment may allow to distinguish patients with different capacity to control infection and reconstitute antiviral function. DESIGN: HBV dextramer+CD8 T cells were analysed ex vivo for coexpression of checkpoint/differentiation markers, transcription factors and cytokines in 35 patients with HLA-A2+chronic hepatitis B (CHB) and in 29 control HBsAg negative CHB patients who seroconverted after NUC treatment or spontaneously. Cytokine production was also evaluated in HBV peptide-stimulated T cell cultures, in the presence or absence of antioxidant, polyphenolic, PD-1/PD-L1 inhibitor and TLR-8 agonist compounds and the effect on HBV-specific responses was further validated on additional 24 HLA-A2 negative CHB patients. RESULTS: Severely exhausted HBV-specific CD8 T cell subsets with high expression of inhibitory receptors, such as PD-1, TOX and CD39, were detected only in a subgroup of chronic viraemic patients. Conversely, a large predominance of functionally more efficient HBV-specific CD8 T cell subsets with lower expression of coinhibitory molecules and better response to in vitro immune modulation, typically detected after resolution of infection, was also observed in a proportion of chronic viraemic HBV patients. Importantly, the same subset of patients who responded more efficiently to in vitro immune modulation identified by HBV-specific CD8 T cell analysis were also identified by staining total CD8 T cells with PD-1, TOX, CD127 and Bcl-2. CONCLUSIONS: The possibility to distinguish patient cohorts with different capacity to respond to immune modulatory compounds in vitro by a simple analysis of the phenotypic CD8 T cell exhaustion profile deserves evaluation of its clinical applicability.

Nebulized hyaluronic acid improves nasal symptoms after orthognathic surgery: a randomized clinical trial.

PURPOSE: After maxillary osteotomy in orthognathic surgery, patients report nasal breathing discomfort in early postoperative period. Topical hyaluronic acid (HA) has been proven to have beneficial effects on the upper airway tract mucosa. This prospective randomized controlled study was designed to analyze the effect on nasal obstruction of nebulized HA during the recovery process after maxillary osteotomy. METHODS: Patients were randomized to control and treatment groups. The postoperative treatment differed only for additional nebulized HA provided to the treatment group. The level of nasal obstruction, and its impact on quality of life, was assessed every 3 days for the first 15 days postoperatively using a questionnaire. Demographic and other variables (maxillary osteotomy type and surgical movements) were analyzed. Differences in quantitative data were tested using Student's t-test, the Mann-Whitney U test, and mixed repeated measures ANOVA. RESULTS: Twenty-four subjects were included in each group; differences in age, sex, type of maxillary osteotomy, and movements were non-statistically significative. At the beginning of treatment (T0), the two groups had comparable questionnaire scores regarding nasal breathing discomfort (p >0.05), whereas statistically significant differences were found at days 3, 6, 9, and 12 (p <0.05). A significant decrease in nasal breathing discomfort over time was observed in both groups, with trends that differed between the two, indicating faster improvement in the treatment group. CONCLUSION: Nebulized HA can be a useful additional treatment in early postoperative period after orthognathic surgery. Patients reported more rapid improvement of nasal respiratory symptoms, indicating a potential role for HA in reducing recovery time and patient discomfort after maxillary surgery.

The prognostic role of metastatic lymph node ratio in colon cancer: a retrospective cohort study on 241 patients in a single center.

BACKGROUND: The detection of nodal status is based on examination of lymph nodes (LN) after the tumor surgical resection and the current guidelines recommend examining at least 12 regional LN. An inadequate number of examined LN may lead to a lower N stage or to a false-negative nodal disease. To overcome these issues, many authors proposed to consider the metastatic lymph node ratio (mLNR). MLNR is the ratio of the number of metastatic LN to the number of examined LN. METHODS: Two hundred forty-one colon cancer (CC) specimens from patients who had undergone surgical resection between January 2010 and December 2015 at the General Surgery Unit of Parma University Hospital were analyzed. mLNR, which is defined as the ratio of the number of positive LN to the number of examined LN, was calculated in CCs with LN metastasis. In this study we focused on the following mLRN cutoffs: <0.15, 0.15-0.3 and >3 and we evaluated the prognostic implication of mLNRs. RESULTS: Regarding the impact of examined LN on involved LN in CC, our results showed that the number of involved LN increased with the increasing number of examined LN (P=0.03). We found a significant correlation between OS and RFS rate of patients with CCs and mLNR. Patients with mLNR<0.15 were associated with better OS and RFS rate whereas patients with mLNR>0.3 were associated with worse OS and RFS rate. OS rate for patients with a mLNR<0.15 was 95.24% (89-100%) at 1 year, 83.27% (72.7-95.4%) at 3 years and 68.07% (55.1-84.1%) at 5 years whereas patients with a mLNR>0.3 had an OS rate of 51.7% (34.6-77.3%) at 1 year, 36.55% (20.08-64.3%) at 3 years and 31.33% (16.5-59.4%) at 5 years. RFS rate for patients with a mLNR<0.15 was 100% (100-100%) at 1 year, 92.2% (84-100%) at 3 years and 85.2% (73.8-98.31%) at 5 years whereas patients with a mLNR>0.3 had a RFS of 63.2% (42.8-93.58%) at 1 year and 54.2% (33.1-88.93%) at 3 and 5 years. CONCLUSIONS: The prognostic value of pN stage could be more accurate if we consider both the number of LN metastasis and harvested LN. This can be achieved by using the mLNR that can be a useful tool in daily practice to predict the prognosis of patients who undergone surgery for CC.

Carotid endarterectomy in asymptomatic octogenarians: Outcomes at 30 days and 5 years.

BACKGROUND: The following study investigated the 30-day and 5-year relative survival rate and freedom from neurological events in asymptomatic carotid stenosis (ACS) octogenarians who had undergone elective carotid endarterectomy (CEA). METHODS: Between January 2008 and June 2014, a retrospective review was conducted on ACS patients who had undergone elective CEA. The patients' sample was divided into two groups: Group A (GA) included octogenarians and Group B (GB) included younger patients. The GA patients were subjected to a risk-scoring system and follow-up. The two groups were compared analysing the following primary endpoints: 30-day mortality, stroke, stroke/death and acute myocardial infarction (AMI); GA patients' survival rate and freedom from neurological events at 5 years. The 30-day secondary endpoints included carotid shunting, redo surgical, need for general anaesthesia with preserved consciousness (GAPC) conversion and length of hospital stay. RESULTS: We identified 620 patients with ACS, of them 144 (23.2%) belonged to the GA and 476 (76.8%) belonged to the GB. No statistical difference between the two groups was found regarding the primary and secondary endpoints. One hundred nineteen of 144 GA patients (82.6%) underwent the follow-up; the median follow-up was 78.3 months. The GA patients' 5-year survival rate was 62%, while freedom from cerebral events was 94.9%. Analysis regarding GA patients' 5-year survival rate revealed a significantly lower percentage among the patients with a severe risk score compared with those with a moderate risk score (respectively, 29.5% vs 67.7%; p = .005). The multivariate analysis showed that chronic obstructive pulmonary disease (COPD) and chronic kidney disease (CKD) were independently associated with lower survival. CONCLUSIONS: The 30-day outcomes of CEA in octogenarians are comparable to those in younger patients. Comprehensive life expectancy and preoperative score, rather than age alone, should be taken into account before performing CEA on octogenarian patients, considering the short- and long-term efficacy in stroke prevention.

The duration of successive epileptic seizures is monotonically correlated in neonates.

OBJECTIVE: Prolonged neonatal seizures are often due to severe acute brain injuries and are known to be harmful to the brain. No predictors have yet been identified to distinguish at an early time-point between brief and long seizures. We investigated the duration of seizures in neonates to determine the relationship between the duration of a seizure and that of subsequent seizures. METHODS: We retrospectively reviewed video-electroencephalogram confirmed seizures of 30 preterm and 36 full-term neonates selected from patients admitted to the neonatal intensive care unit of Parma University Hospital. The duration and relationship between successive seizures were investigated. Statistical models were performed to evaluate the risk of long-lasting ictal events among neonates with seizures. RESULTS: A positive monotonic relationship between the duration of successive seizures was identified. Most seizures were brief. No significant differences in seizure duration were found between preterm and full-term neonates, although a borderline significance emerged. CONCLUSION: Neonatal seizures are usually brief, and as the seizure duration increases, the duration of the subsequent seizures tends to increase. We also suggest that full-term neonates could be at higher risk of experiencing long seizures compared to preterm neonates. In summary, estimating the seizure duration is critical to evaluating the optimal timing of therapeutic interventions and can help to predict how seizures evolve.

It Takes Two to Tango: Potential Prognostic Impact of Circulating TGF-Beta and PD-L1 in Pancreatic Cancer.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly devastating disease with rising incidence and poor prognosis. The lack of reliable prognostic biomarkers hampers the individual evaluation of the survival and recurrence potential. Methods: Here, we investigate the value of plasma levels of two potential key players in molecular mechanisms underlying PDAC aggressiveness and immune evasion, soluble TGF-beta (sTGF-beta) and sPD-L1, in both metastatic and radically-resected PDAC. To this aim we prospectively enrolled 38 PDAC patients and performed appropriate statistical analyses in order to evaluate their correlation, and role in the prediction of disease relapse/progression, and patients' outcome. Results: Metastatic patients showed lower levels of circulating sTGF-beta and higher levels of sPD-L1 compared to radically-resected patients. Moreover, a decrease in sTGF-beta levels (but not sPD-L1) was significantly associated with disease relapse in radically-resected patients. We also observed lower sTGF-beta at disease progression after first-line chemotherapy in metastatic patients, though this change was not statistically significant. We found a significant correlation between the levels of sTGF-beta and sPD-L1 before first-line chemotherapy. Conclusions: These findings support the possible interaction of TGF-beta and PD-L1 pathways and suggest that sTGF-beta and sPD-L1 might synergize and be new potential blood-based biomarkers.

Clinical characteristics of a large cohort of patients with narcolepsy candidate for pitolisant: a cross-sectional study from the Italian PASS Wakix® Cohort.

INTRODUCTION: Narcolepsy is a chronic and rare hypersomnia of central origin characterized by excessive daytime sleepiness and a complex array of symptoms as well as by several medical comorbidities. With growing pharmacological options, polytherapy may increase the possibility of a patient-centered management of narcolepsy symptoms. The aims of our study are to describe a large cohort of Italian patients with narcolepsy who were candidates for pitolisant treatment and to compare patients' subgroups based on current drug prescription (drug-naïve patients in whom pitolisant was the first-choice treatment, switching to pitolisant from other monotherapy treatments, and adding on in polytherapy). METHODS: We conducted a cross-sectional survey based on Italian data from the inclusion visits of the Post Authorization Safety Study of pitolisant, a 5-year observational, multicenter, international study. RESULTS: One hundred ninety-one patients were enrolled (76.4% with narcolepsy type 1 and 23.6% with narcolepsy type 2). Most patients (63.4%) presented at least one comorbidity, mainly cardiovascular and psychiatric. Pitolisant was prescribed as an add-on treatment in 120/191 patients (62.8%), as switch from other therapies in 42/191 (22.0%), and as a first-line treatment in 29/191 (15.2%). Drug-naive patients presented more severe sleepiness, lower functional status, and a higher incidence of depressive symptoms. CONCLUSION: Our study presents the picture of a large cohort of Italian patients with narcolepsy who were prescribed with pitolisant, suggesting that polytherapy is highly frequent to tailor a patient-centered approach.

The influence of Mediterranean diet in acne pathogenesis and the correlation with insulin-like growth factor-1 serum levels: Implications and results.

Acne is a chronic inflammatory disease of the pilosebaceous unit, and its etiology is complex and multifactorial. The role of the diet in its pathogenesis is still debated. The purpose of this study was to assess the association between MD and IGF-1 in acne patients and, as secondary objective, the role of systemic treatment on IGF-1 serum levels, in accordance with the patients' diet. This study included 35 patients aged 14-30 years affected by acne and treated in line with the EDF guidelines. Patients were divided into 2 groups based on a questionnaire score assessing the adherence to the Mediterranean diet: the Mediterranean Group (score ≥6) and the Western Group (score< 5). IGF-1 serum levels were measured in all patients before and after treatment and then compared to healthy population. IGF-1 levels were higher in patients than in controls and in the Western group than in the Mediterranean group. We speculate that the Mediterranean diet can have a protective role in the pathogenesis of acne by acting on the systemic route of IGF-1.

COVID-19 outbreak impact on health professionals: A survey on the Italian radiographer experience.

AIM: To evaluate the impact of the Phase 1 COVID-19 (C19) outbreak on Italian Radiographers. MATERIAL AND METHODS: COVID-19 has spread rapidly worldwide. Many patients underwent radiological examinations, leading to a high risk of infection within the radiology department's staff. Italy was the first-hit European country to face the COVID-19 outbreak and the impact on radiographers was huge. An online survey was disseminated to investigate the involvement and working environment of Italian radiographers during the first outbreak of COVID-19. RESULTS: Of the 840 responders, 65% were men. The majority of the responding Health-care Workers (HCW) was represented by radiographers (96%), from high-prevalence regions (82%; p<.05). Forty-five percent were involved in the activation of the protocol for the management of COVID-19 positive patients, without exhaustive indication for Plain Radiography and Computed Tomography (CT). Only 17% of hospitals counted on available guidelines for serious infections (p<0.05). Diagnostic examinations were mainly performed by a single radiographer (62%). Many professionals (69%) confirmed wearing all indispensable PPE in case of COVID-19 positive patients. CONCLUSION: The primary objective of management strategies should be to redact standardized policies for the safeguarding of patient's health and operator's safety. All front-line workers, including radiographers working in diagnostic services, should be involved in the decision-making process to generate wellness and awareness.

Cognitive reserve index and functional and cognitive outcomes in severe acquired brain injury: A pilot study.

BACKGROUND: Many variables affect outcome after brain injury. Cognitive reserve (CR) is a subjective factor that reflects a set of personal characteristics and that differentiates individuals. It may influence an individual's capacity to react to brain injury. OBJECTIVE: To study the effects of cognitive reserve on functional and cognitive outcome at the end of rehabilitation, in patients with severe acquired brain injury (sABI), by means of the Cognitive Reserve Index questionnaire (CRIq). METHODS: We report a retrospective study of a continuous series of sABI patients on first admission to a rehabilitation center. Disability and cognitive outcomes were recorded. RESULTS: In the 94 patients enrolled, the assessments after rehabilitation showed a significant gain measured with the disability Rating Scale for patients with a higher CR (CRIq≥ 85). A significant negative correlation was found: between CRIq scores and the interval elapsing before first access to neuropsychological assessment, between CRIq scores, especially level of education, and tests that measure the same domain (attention). CONCLUSIONS: Improvements in overall and cognitive disability emerged, but CR did not seem to substantially influence outcome in this sample of patients. This result may be partly due to the clinical severity of the population studied and the sample's dimension, although quantitatively representative of the population.