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Annalisa Pace,1,2 Alessandro Milani,1 Valeria Rossetti,1 Giannicola Iannella,1– 3 Antonino Maniaci,4 Salvatore Cocuzza,4 Danilo Alunni Fegatelli,5 Annarita Vestri,5 Giuseppe Magliulo1 1Organi di Senso Department, Sapienza University, Rome, Italy; 2Scienze Chirurgiche Department, Sapienza University, Rome, Italy; 3Department of Head-Neck Surgery, Morgagni Pierantoni Hospital, Forlì, Italy; 4Otorinolaringoiatria Department, University of Catania, Catania, Italy; 5Department of Public Health and Infectious Diseases, Sapienza University, Rome, ItalyCorrespondence: Annalisa Pace, Organi di Senso Department, Sapienza University, Viale dell’Università 33 Rome, 00165, Italy, Tel +393203581431, Fax +390649976817, Email annalisapace90@gmail.comPurpose: Obstructive sleep apnoea (OSA) is a common disease with significantly related complications. Since a connection between the vestibular nucleus and sleep regulator pathways has been demonstrated, vestibular evaluation in OSA patients was partially studied and none used functional head impulse test (fHIT) for this purpose. This paper aimed at evaluating the vestibular function in patients affected by OSA using fHIT, selecting patients who did not present any other related to cardiovascular, neurological, or metabolic diseases.Patients and Methods: Patients enrolled had a diagnosis of OSA by polysomnography type III and were cataloged according to American Association of Sleep Medicine criteria. Each patient underwent fHIT. Statistical significance was set at 0.05.Results: A total of 85 patients were enrolled in the study of which 50 had a diagnosis of OSA and were included in the case group, while 35 belonged to the control group. In 88.6% of subjects of the case group was evidenced a vestibular impairment with a substantial difference between the two study groups (p< 0.05).Conclusion: The results show that the incidence of vestibular lesions in patients with obstructive sleep apnoea is underestimated and that fHIT can identify these lesions early.Keywords: obstructive sleep apnea, vestibular system, functional head impulse test, vestibular ocular reflex, sleep regulator pathways

Purpose: To assess the tear levels of a set of apoptotic, matrix-degrading and antioxidant biomarkers, including Metalloproteinase 9 (MMP9), High Mobility Group Box 1 (HMGB1) and Superoxide Dismutase 3-Extracellular (SOD3)., Methods: Sandwich-ELISA commercial kits were used to test the expression of the three tear biomarkers in the lacrimal fluid of eligible participants. Linear logistic regression analysis was performed todetermine whether the set of tear biomarkers could be associated with clinically manifest keratoconus. ROC curve analysis using 10-fold cross-validation was performedto evaluate the prediction accuracy of the model., Results: Eighty-one participants aged 30-48 years old were enrolled in this study; 48 were patients with keratoconus and 33 were age-matched healthy subjects. The linear combination of the three tear biomarkers levels (AUC = 0.811; CI 95 %: 0.712-0.911) accurately indicated the existence of keratoconus; higher levels of MMP9 (Odd Ratio: 1.069; CI 95 %: 1.029-1.130) and HMGB1 (OR: 1.011; CI 95 %: 1.003-1.022) and lower levels of SOD3 (OR: 0.994; CI 95 %: 0.989-0.997) were significantly associated with a higher probability of keratoconus., Conclusion: Multivariable analysis of the set of tear levels of MMP9, HMGB1 and SOD3 biomarkers confirmed a chronic state of inflammation in the ocular surface of patients with keratoconus., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Essential tremor (ET) is a heterogeneous disorder characterized by bilateral upper limbs action tremor and, possibly, neurological signs of uncertain significance, including voluntary movement abnormalities and cognitive disturbances, i.e., the so-called 'soft' signs configuring the ET-plus definition. While motor and cognitive disturbances often coexist in ET, their interrelationship remains largely unexplored. Here we aim to further investigate the relationship between motor symptoms, objectively assessed through kinematic analysis, and cognitive dysfunctions in ET. Seventy ET patients underwent clinical examination, as well as kinematic recordings of tremor and finger tapping and a thorough cognitive assessment. We then tested clinic-demographic and kinematic differences between patients with and without cognitive abnormalities, i.e., with mild cognitive impairment (MCI). Correlation analysis served to explore potential associations between kinematic and cognitive data. Forty-three ET patients (61.42%) had MCI. ET-MCI patients exhibited reduced movement velocity during finger tapping compared to those with normal cognition (p < 0.001). Lower movement velocity during finger tapping was associated with poorer cognitive performance. Namely, we observed a correlation between movement velocity and performance on the Babcock Story Immediate and Delayed Recall Test (r = 0.52 and r = 0.45, both p < 0.001), as well as the interference memory task at 10 and 30 s (r = 0.3, p = 0.008 and r = 0.2, p = 0.03). In this study, we have provided data for a better pathophysiological interpretation of motor and cognitive signs in ET, including the role played by the cerebellum or extra-cerebellar areas, which possibly underpin both signs., (© 2024. The Author(s).)

Objective: To report variants in 26 candidate genes and describe the clinical features of Italian patients with keratoconus (KC)., Subjects/methods: Sixty-four patients with a confirmed diagnosis of KC were enrolled in this genetic association study. Patients were classified into two study groups according to whether they had a confirmed diagnosis of progressive or stable KC. A purpose-developed Next Generation Sequencing (NGS) panel was used to identify and analyse the coding exons and flanking exon/intron boundaries of 26 genes known to be associated with KC and corneal dystrophies. Interpretation of the pathogenic significance of variants was performed using in silico predictive algorithms., Result: The targeted NGS research identified a total of 167 allelic variants of 22 genes in the study population; twenty-four patients had stable keratoconus (n. 54 variants) and forty patients had progressive disease (n. 113 variants). We identified genetic variants of certain pathogenic significance in five patients with progressive KC; in addition, eight novel genetic variants were found in eight patients with progressive KC. Mutations of FLG, LOXHD1, ZNF469, and DOCK9 genes were twice more frequently identified in patients with progressive than stable disease. Filaggrin gene variants were found in 49 patients (76% of total), of whom 32 patients (80% of progressive KC group) had progressive disease., Conclusions: Targeted NGS research provided new insights into the causative effect of candidate genes in the clinical phenotype of keratoconus. Filaggrin mutations were found to represent a genetic risk factor for development of progressive disease in Italy., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Data describing the use of extracorporeal membrane oxygenation (ECMO) in pediatric acute liver failure (PALF) are scarce. Thus, we aimed to describe the use of ECMO in patients with PALF using the data from the Extracorporeal Life Support Organization (ELSO) Registry between January 1, 2010, to December 31, 2022. We described patients' characteristics at ECMO initiation, outcome, and factors associated with mortality. A total of 335 children underwent ECMO support in the context of PALF. Veno-arterial (VA) ECMO was the most prevalent mode (66.6%), followed by veno-venous (VV) ECMO (33.4%). Extracorporeal cardiopulmonary resuscitation (ECPR) was used in 21.5% of the cardiac arrest. In-hospital mortality was 66.6%. Both higher lactate (OR 1.128, CI 1.06-1.209, p < 0.001) and PaCO 2 (OR 1.022, CI 1.001-1.047, p 0.05) levels before ECMO reported greater odds of mortality. Low body weight, persistence of hyperlactatemia (OR 0.985, CI 0.973-0.997, p 0.013), and hyperbilirubinemia (OR 2.477, CI 1.042-6.100, p 0.045) after 24 h from ECMO deployment were associated to greater odds of mortality., Conclusions: Our results suggest that the use of ECMO for the management of respiratory and cardiac failure in patients with PALF should be considered with caution and that further research is needed to understand its role in this specific high-risk population., What Is Known: • Pediatric acute liver failure (PALF) is a clinical syndrome associated with significant morbidity and mortality. • Data on the use of extracorporeal membrane oxygenation (ECMO) in the context of PALF are scarce and controversial., What Is New: • ECMO to manage acute respiratory and/or cardiac failure in the context of PALF should be considered with caution. • Bleeding and thrombotic complications in children with acute liver failure receiving ECMO are similar to the ones reported in the general pediatric population., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

There are minimal data describing use of extracorporeal membrane oxygenation (ECMO) in pediatric patient after a liver transplantation (LT). This study aimed at describing ECMO run in this specific situation using the data from Extracorporeal Life Support Organization (ELSO) Registry between January 1, 2010, to December 31, 2022. We described patients' characteristics at ECMO initiation, outcome and mortality risk factors. We identified 27 patients with a median age of 2.7 years (interquartile range (IQR) = 1.5-9.9). Main indication for ECMO support was respiratory (14/27 [52%]) followed by extracorporeal cardiopulmonary resuscitation (ECPR) (7/27 [26%]) and cardiac (6/27 [22%]). Overall in-hospital mortality was 63% (17/27). Mortality rate according to ECMO indications was 50% for both respiratory and cardiac failure and reached 100% for ECPR patients. Overall, nonsurvivors experienced significantly more complications under ECMO support ( p = 0.007). Main on-ECMO complications were hemorrhagic (11/27 [41%]) and thrombotic (7/27 [26%]). No clinical or biologic factors was predictive of patients' outcome. Our results suggest that ECMO support is a viable option for cardiac and respiratory indications after pediatric LT. Occurrence of complications while on ECMO are associated with unfavorable outcomes. The extremely high mortality rate in ECPR patients merits further research., Competing Interests: P.R. is the executive director of ELSO and R.R.T. reports a relationship with United States Department of Defense Pharmacoeconomic Center that includes funding grants. R.R.T. reports a relationship with Society of Critical Care Medicine that includes funding grants, and also reports a relationship with Extracorporeal Life Support Organization that includes funding grants. The other authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)

Purpose: To validate the ability of theranostic imaging biomarkers in assessing corneal cross-linking (CXL) efficacy in flattening the maximum keratometry (K max ) index., Design: Prospective, randomized, multicenter, masked clinical trial (ClinicalTrails.gov identifier, NCT05457647)., Participants: Fifty patients with progressive keratoconus., Intervention: Participants were stratified to undergo epithelium-off (25 eyes) and epithelium-on (25 eyes) CXL protocols using an ultraviolet A (UV-A) medical device with theranostic software. The device controlled UV-A light both for performing CXL and assessing the corneal riboflavin concentration (riboflavin score) and treatment effect (theranostic score). A 0.22% riboflavin formulation was applied onto the cornea for 15 minutes and 20 minutes in epithelium-off and epithelium-on protocols, respectively. All eyes underwent 9 minutes of UV-A irradiance at 10 mW/cm 2 ., Main Outcome Measures: The primary outcome measure was validation of the combined use of theranostic imaging biomarkers through measurement of their accuracy (proportion of correctly classified eyes) and precision (positive predictive value) to classify eyes correctly and predict a K max flattening at 1 year after CXL. Other outcome measures included change in K max , endothelial cell density, uncorrected and corrected distance visual acuity, manifest spherical equivalent refraction and central corneal thickness 1 year after CXL., Results: Accuracy and precision of the theranostic imaging biomarkers in predicting eyes that had >0.1 diopter (D) of K max flattening at 1 year were 91% and 95%, respectively. The K max value significantly flattened by a median of -1.3 D (IQR, -2.11 to -0.49 D; P < 0.001); both the uncorrected and corrected distance visual acuity improved by a median of -0.1 logarithm of the minimum angle of resolution (logMAR; IQR, -0.3 to 0.0 logMAR [P < 0.001] and -0.2 to 0.0 logMAR [P < 0.001], respectively). No significant changes in endothelial cell density (P = 0.33) or central corneal thickness (P = 0.07) were noted 1 year after surgery., Conclusions: The study demonstrated the efficacy of integrating theranostics in a UV-A medical device for the precise and predictive treatment of keratoconus with epithelium-off and epithelium-on CXL protocols. Concentration of riboflavin and its UV-A light mediated photoactivation in the cornea are the primary factors determining CXL efficacy., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To estimate the prevalence of keratoconus in a population of subjects undergoing first eye examination in an eye clinic in Italy., Methods: A single-center, cross-sectional, study was conducted involving patients who underwent first eye examination at an eye clinic in Rome between September 2021 and June 2022. The prevalence of keratoconus was determined by Placido-disk corneal topography using the maximum keratometry (K max ) value and the Cone Magnitude and Location Index (CLMI) for keratoconus screening. Subjective analysis was performed by two experienced corneal specialists, who classified the outcome into two groups: normal and keratoconus. Risk factors, including family history of keratoconus, allergy or atopy, thyroid disease, eye rubbing habit and gender were also examined., Results: A total of 512 subjects between 7 and 81 years old were evaluated. The inter-observer agreement to classify subjects in normal or keratoconus group was excellent (k = 1.0); the estimated prevalence in the specific population was 2.1%. Presence of positive family history (9% of keratoconus vs 5% normal), concomitant allergy or atopy (27% vs 9%) and eye rubbing habit (18% vs 4%) were associated with a higher risk of disease., Conclusion: This study reported a high estimated prevalence of keratoconus in a metropolitan area of Italy, as found in recent studies in the Mediterranean and Middle East countries. Screening for keratoconus is highly recommendable and easily feasible with corneal topography under expert supervision and may be indicated primarily in young population to improve early detection and prompt therapeutic management for halting disease progression., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: The aim of this study was to assess accuracy of the mean corneal stiffness ( kc , N/m) parameter to discriminate between patients with keratoconus and age-matched healthy subjects., Methods: Dynamic Scheimpflug imaging tonometry was performed with Corvis ST (Oculus Optikgeräte GmbH, Germany) in patients with keratoconus (n = 24; study group) and age-matched healthy subjects (n = 32; control). An image processing algorithm was developed to analyze the video sequence of the Corvis ST air-puff event and to determine the geometric and temporal parameters that correlated with the corneal tissue biomechanical properties. A modified 3-element viscoelastic model was used to derive the kc parameter, which represented the corneal tissue resistance to deformation under load. Receiver operating characteristic curves were used to assess the overall diagnostic performance for determining the area under the curve, sensitivity, and specificity of the kc in assessing the corneal tissue deformation to the Corvis ST air-puff event in keratoconus and control eyes. The Corvis Biomechanical Index ( CBI ) was analyzed for external validation., Results: The kc parameter was significantly different between keratoconus and controls ( P < 0.001), ranging from 24.9 ±3.0 to 34.2 ±3.5 N/m, respectively. It was highly correlated with CBI (r = -0.69; P < 0.001); however, the kc parameter had greater specificity (94%) than CBI (75%), whereas the 2 biomarkers had similar area under the curve (0.98 vs. 0.94) and sensitivity (96% vs. 92%) in predicting the occurrence of keratoconus., Conclusions: The kc parameter extracted by video processing analysis of dynamic Scheimpflug tonometry data was highly accurate in discriminating patients with clinically manifest keratoconus compared with controls., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: High CHA 2 DS 2 -VASc score (Congestive heart failure, Hypertension, Age > 75 years, Diabetes mellitus, prior Stroke or transient ischemic attack or thromboembolism, Vascular disease, Age 65-74 and Sex category) was associated with adverse clinical outcomes in different settings. The aim of the present study was to evaluate the association between CHA 2 DS 2 -VASc score and R 2 CHA 2 DS 2 -VASc score (which includes renal impairment) with in-hospital mortality and length of hospital stay in patients hospitalized in an internal medicine ward., Methods: We enrolled 983 consecutive patients admitted during 3 years in an internal medicine ward. R 2 CHA 2 DS 2 -VASc score was calculated by adding 2 points to CHA 2 DS 2 -VASc for the presence of chronic kidney disease (CKD), defined according to K-DOQI. The primary outcome was a composite of all-cause mortality and length of hospital stay > 10 days., Results: Patients with CKD stages 3-5 presented with increased CHA 2 DS 2 -VASc vs stages 1-2 (p < 0.001). The composite outcome occurred in 47.3% of inpatients. Multivariable linear logistic regression analyses adjusted for presence of infectious diseases and cancer, with the occurrence of composite outcome showed an adjusted OR of 1.349 (95% CI 1.248-1.462) and 1.254 (95% CI 1.179-1.336) for CHA 2 DS 2 -VASc and R 2 CHA 2 DS 2 -VASc scores, respectively. No differences were found in the association between CHA 2 DS 2 -VASc and R 2 CHA 2 DS 2 -VASc scores with the composite outcome (AUC 0.631 vs 0.630), and furthermore, adding the presence/absence of infectious diseases during hospitalization and positive cancer history to the models increased the AUC (0.667 and 0.663)., Conclusions: Incrementally higher CHA 2 DS 2 -VASc score is associated with increased length of hospital stay and mortality in patients hospitalized in an internal medicine ward, regardless of the presence of CKD., (© 2023. The Author(s).)

Aims: The multi-systemic effects of heart failure (HF) resemble the spread observed during cancer. We propose a new score, named HLM, analogous to the TNM classification used in oncology, to assess the prognosis of HF. HLM refers to H: heart damage, L: lung involvement, and M: systemic multiorgan involvement. The aim was to compare the HLM score to the conventional New York Heart Association (NYHA) classification, American College of Cardiology/American Heart Association (ACC/AHA) stages, and left ventricular ejection fraction (LVEF), to assess the most accurate prognostic tool for HF patients., Methods and Results: We performed a multicentre, observational, prospective study of consecutive patients admitted for HF. Heart, lung, and other organ function parameters were collected. Each patient was classified according to the HLM score, NYHA classification, ACC/AHA stages, and LVEF assessed by transthoracic echocardiography. The follow-up period was 12 months. The primary endpoint was a composite of all-cause death and rehospitalization due to HF. A total of 1720 patients who completed the 12 month follow-up period have been enrolled in the study. 520 (30.2%) patients experienced the composite endpoint of all-cause death and rehospitalization due to HF. 540 (31.4%) patients were female. The mean age of the study population was 70.5 ± 12.9. The mean LVEF at admission was 42.5 ± 13%. Regarding the population distribution across the spectrum of HLM score stages, 373 (21.7%) patients were included in the HLM-1, 507 (29.5%) in the HLM-2, 587 (34.1%) in the HLM-3, and 253 (14.7%) in the HLM-4. HLM was the most accurate score to predict the primary endpoint at 12 months. The area under the receiver operating characteristic curve (AUC) was greater for the HLM score compared with the NYHA classification, ACC/AHA stages, or LVEF, regarding the composite endpoint (HLM = 0.645; NYHA = 0.580; ACC/AHA = 0.589; LVEF = 0.572). The AUC of the HLM score was significantly better compared with the LVEF (P = 0.002), ACC/AHA (P = 0.029), and NYHA (P = 0.009) AUC., Conclusions: The HLM score has a greater prognostic power compared with the NYHA classification, ACC/AHA stages, and LVEF assessed by transthoracic echocardiography in terms of the composite endpoint of all-cause death and rehospitalization due to HF at 12 months of follow-up., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Malnutrition is a well-known risk factor for morbidity and mortality in many clinical settings and only few studies assessed the role of malnutrition on systemic sclerosis (SSc) patients' outcomes. The aim of this retrospective study was to evaluate the role of malnutrition as a predictive risk factor for mortality and/or hospitalization in SSc patients during a 4-year follow-up., Methods: One hundred and one SSc patients were included in the study. Biochemical analyses, disease activity index, disease severity scale and anthropometric data were recorded at enrollment. Malnutrition was assessed by the Global Leadership Initiative on Malnutrition (GLIM) criteria., Results: Malnutrition according to GLIM criteria was found in 22 patients (21.8%). During a 4-year follow-up, 20 (19.8%) SSc patients died or were hospitalized for all causes and 11 of them (55.0%) were malnourished. Kaplan-Meier curves showed that event free-survival for composite end-point of mortality and risk of hospitalization was significantly shorter in malnourished than in non-malnourished patients (p<0.001). The survival probability at 4 years was 0.885 (95% CI=0.818-0.959) in the non-malnourished group and 0.500 (95% CI=0.329-0.759) in the malnourished group (p<0.001). In multivariate analysis, malnutrition [HR=4.380 (95% CI=1.706-11.243), p = 0.002] was the most significant predictive risk factor for the composite end-point. Also, female gender [HR=0.157 (95% CI=0.055-0.449), p<0.001], age [HR=1.0450 (95% CI=1.011-1.090), p = 0.012] and disease severity scale [HR=1.269 (95% CI=1.089-1.479), p = 0.002] were predictive factors for the composite end-point., Conclusions: Malnutrition according to GLIM criteria represents a significant predictive risk factor for composite end-point of mortality and risk of hospitalization in SSc patients., Competing Interests: Declaration of Competing of Interest None., (Copyright © 2023 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

[Correction Notice: An Erratum for this article was reported online in Psychological Trauma: Theory, Research, Practice, and Policy on May 08 2023 (see record 2023-69929-001). In the original article, paragraphs 1 through 3 of the main text and the first paragraph under "PTSD and CPTSD Symptoms" in the Methods section were rewritten to avoid text similarity with that of a previously published article "Evidence of Distinct Profiles of ICD-11 Post-Traumatic Stress Disorder (PTSD) and Complex PTSD in a South African Sample," by James Rink and Gosia Lipinska (European Journal of Psychotraumatology, 2020, Vol. 11, No. 1, Article 1818965, https:// doi.org/10.1080/20008198.2020.1818965). All versions of this article have been corrected.] Objective: This study investigated ICD-11 posttraumatic stress disorder (PTSD) and complex PTSD (CPTSD) symptom profiles and their premigration, postmigration, and demographic predictors in a treatment-seeking sample of asylum-seekers in Agadez (Niger)., Method: Participants were 126 asylum-seekers hosted in a large, isolated reception camp in the desert surroundings of Agadez (humanitarian site) or in a number of small urban hosting facilities ( cases de passages ) who completed measures of trauma exposure and PTSD/CPTSD symptoms. Latent class analysis (LCA) was used to identify symptom profiles, and predictors of class membership were identified via multinomial logistic regression., Results: More asylum seekers met the criteria for CPTSD (74.6%) than PTSD (19.8%) and no gender differences were observed. LCA results identified two distinct groups: (a) a CPTSD class (69.0%); and (b) a PTSD class (31.0%). Membership in the CPTSD class was significantly predicted by the early age of the first traumatic event, levels of functional impairment and reception conditions. Specifically, those in the CPTSD class were more likely to live in the humanitarian site compared with those in the PTSD class., Conclusion: This study supported the validity of the ICD-11 construct of CPTSD in an asylum-seeker sample living in a low-income country. Moreover, the findings suggest that not only premigration factors (i.e., the early age of the first trauma) but also postmigration stressors (i.e., precarious reception conditions in large, isolated facilities) are important predictors of CPTSD symptoms with important implications regarding reception policies and the prevention of trauma-related mental disorders in asylum seekers and refugees. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The Assessment of theranostic guided riboflavin/UV-A corneal cross-linking for treatment of keratoconus (ARGO; registration number NCT05457647) clinical trial tests the hypothesis that theranostic-guided riboflavin/UV-A corneal cross-linking (CXL) can provide predictable clinical efficacy for halting keratoconus progression, regardless of treatment protocol, i.e., either with or without epithelial removal. Theranostics is an emerging therapeutic paradigm of personalized and precision medicine that enables real-time monitoring of image-guided therapy. In this trial, the theranostic software module of a novel UV-A medical device will be validated in order to confirm its accuracy in estimating corneal cross-linking efficacy in real time. During CXL procedure, the theranostic UV-A medical device will provide the operator with an imaging biomarker, i.e., the theranostic score, which is calculated by non-invasive measurement of corneal riboflavin concentration and its UV-A light mediated photo-degradation. ARGO is a randomized multicenter clinical trial in patients aged between 18 and 40 years with progressive keratoconus aiming to validate the theranostic score by assessing the change of the maximum keratometry point value at 1-year postoperatively. A total of 50 participants will be stratified with allocation ratio 1:1 using a computer-generated stratification plan with blocks in two treatment protocols, such as epithelium-off or epithelium-on CXL. Following treatment, participants will be monitored for 12 months. Assessment of safety and performance of theranostic-guided corneal cross-linking treatment modality will be determined objectively by corneal tomography, corneal endothelial microscopy, visual acuity testing and slit-lamp eye examination., (© 2022. The Author(s).)

In 2022, three antiviral drugs-molnupiravir, remdesivir and nirmatrelvir/ritonavir-were introduced for treatment of mild-to-moderate COVID-19 in high-risk patients. The aim of this study is the evaluation of their effectiveness and tolerability in a real-life setting. A single-center observational study was set up, with the involvement of 1118 patients, with complete follow-up data, treated between the 5th of January and the 3rd of October 2022 at Santa Maria Goretti's hospital in Latina, Central Italy. A univariable and a multivariable analysis were performed on clinical and demographic data and composite outcome, the persistence of symptoms at 30 days and time to negativization, respectively. The three antivirals showed a similar effectiveness in containing the progression of the infection to severe COVID-19 and a good tolerability in the absence of serious adverse effects. Persistence of symptoms after 30 days was more common in females than males and less common in patients treated with molnupiravir and nirmatrelvir/r. The availability of different antiviral molecules is a strong tool and, if correctly prescribed, they can have a significant role in changing the natural history of infection for frail persons, in which vaccination could be not sufficient for the prevention of severe COVID-19.

In this retrospective comparative study, we evaluated the effectiveness of remdesivir (RDSV) in patients with SARS-CoV-2 pneumonia. Individuals hospitalized between March 2020 and August 2022 at S.M. Goretti Hospital, Latina, with a positive test for SARS-CoV-2 and, concomitantly, pneumonia, were included. The overall survival was the primary endpoint. The composite secondary endpoint included death or progression in severe ARDS at 40 days. The study population was stratified according to treatment into two groups: the RDSV group (patients treated with RDSV-based regimens) and the no-RDSV group (patients treated with any other, not RDSV-based, regimens). Factors associated with death and progression to severe ARDS or death were assessed by multivariable analysis. A total of 1153 patients (632 belonging to the RDSV group and 521 to the no-RDSV group) were studied. The groups were comparable in terms of sex, PaO2/FiO2 at admission, and duration of symptoms before hospitalization. Further, 54 patients (8.5%) in the RDSV group and 113 (21.7%) in the no-RDSV group ( p < 0.001) died. RDSV was associated with a significantly reduced hazard ratio (HR) of death (HR, 0.69 [95% CI, 0.49-0.97]; p = 0.03), compared to the no-RDSV group, as well as a significantly reduced OR of progression in severe ARDS or death (OR, 0.70 [95% CI 0.49-0.98]; p = 0.04). An overall significantly higher survival rate was observed in the RDSV group ( p < 0.001, by log-rank test). These findings reinforce the survival benefit of RDSV and support its routine clinical use for the treatment of COVID-19 patients.

Objectives: Systemic sclerosis (SSc) is a rare autoimmune disease characterized by microvascular damage and fibrosis of the skin and internal organs. Among SSc complications, changes in nutritional status have a negative effect on quality of life and predispose patients to malnutrition. The aim of this exploratory pilot study was to examine whether bioelectrical impedance analysis-derived phase angle (PhA) is a parameter of nutritional status and a marker of mortality in patients with SSc., Methods: Consecutive adult patients with SSc were included in the study. Biochemical analyses, anthropometric data, and bioelectrical impedance analysis assessments were recorded at the time of enrollment. The Malnutrition Universal Screening Tool (MUST) and Global Leadership Initiative on Malnutrition (GLIM) were applied to assess nutritional status., Results: A total of 104 patients with SSc (88 women; median age: 55 y [interquartile range (IQR), 45.5- 66 y]) were enrolled. In patients with SSc and high malnutrition risk according to MUST, mean values of PhA were significantly lower than those of patients with SSc and low malnutrition risk (4° [IQR, 3.7°-4.4°] vs 4.6° [IQR, 4.2°-5.1°]; P = 0.004). Patients with SSc and malnutrition according to the GLIM criteria showed significantly lower PhA than patients with SSc but without malnutrition (3.8° [IQR, 3.5°-4.3°] vs 4.6° [IQR, 4.2°-5.1°]; P < 0.0001). Kaplan-Meier curves demonstrated that overall survival was significantly shorter (34.57 mo [±13.35] vs 48 mo [±0]; P = 0.001) in patients with SSc and PhA <3.75°. In the multivariate analysis, only PhA was a predictive factor for death (hazard ratio: 0.283; 95% confidence interval, 0.083-0.965; P = 0.044)., Conclusions: The data obtained suggest that lower PhA values in patients with SSc are associated with an increased malnutrition risk with MUST, malnutrition with GLIM, and increased mortality. Additional studies are necessary to confirm these preliminary results., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The term voice hearing (VH) refers to the experience of hearing voices in the absence of corresponding external stimuli and is considered a hallucinatory experience. According to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5; American Psychiatric Association [APA], 2013), hallucinations are perception-like experiences that occur without an external stimulus. They are vivid and clear, with the full force and impact of normal perceptions, and not under voluntary control. Specifically, auditory hallucinations involve the perception of sound, most frequently of voices (i.e., auditory verbal hallucinations- AVHs) but sometimes of clicks or other noises, that are not restricted to the period of awakening or the onset of sleep. AVHs are usually experienced as voices, whether familiar or unfamiliar, that are perceived as distinct from the individual's own thoughts.

Background: Bradykinesia is the hallmark feature of Parkinson's disease (PD); however, it can manifest in other conditions, including essential tremor (ET), and in healthy elderly individuals., Objective: Here we assessed whether bradykinesia features aid in distinguishing PD, ET, and healthy elderly individuals., Methods: We conducted simultaneous video and kinematic recordings of finger tapping in 44 PD patients, 69 ET patients, and 77 healthy elderly individuals. Videos were evaluated blindly by expert neurologists. Kinematic recordings were blindly analyzed. We calculated the inter-raters agreement and compared data among groups. Density plots assessed the overlapping in the distribution of kinematic data. Regression analyses and receiver operating characteristic curves determined how the kinematics influenced the likelihood of belonging to a clinical score category and diagnostic group., Results: The inter-rater agreement was fair (Fleiss K = 0.32). Rater found the highest clinical scores in PD, and higher scores in ET than healthy elderly individuals (p < 0.001). In regard to kinematic analysis, the groups showed variations in movement velocity, with PD presenting the slowest values and ET displaying less velocity than healthy elderly individuals (all ps < 0.001). Additionally, PD patients showed irregular rhythm and sequence effect. However, kinematic data significantly overlapped. Regression analyses showed that kinematic analysis had high specificity in differentiating between PD and healthy elderly individuals. Nonetheless, accuracy decreased when evaluating subjects with intermediate kinematic values, i.e., ET patients., Conclusion: Despite a considerable degree of overlap, bradykinesia features vary to some extent in PD, ET, and healthy elderly individuals. Our findings have implications for defining bradykinesia and categorizing patients.

Introduction/objectives: Gastrointestinal tract (GIT) involvement is frequently observed in systemic sclerosis (SSc) and may lead to nutritional impairment. The aim of the study was to assess the prevalence of symptoms related to GIT involvement and to analyze the possible association between gastrointestinal symptoms and low muscularity in SSc patients., Methods: Sixty-nine consecutive patients (60 females, median age 53 (IQR 43-63), body mass index (BMI) 23.2 (IQR 20.9-24.6) kg/m 2 ) with diagnosis of SSc admitted to our Scleroderma Unit were enrolled. Clinical status, anthropometric data, and bioelectrical impedance (Inbody 770, USA) analysis-assessed Fat-Free Mass Index (FFMI) were recorded upon enrollment. UCLA questionnaire was used to quantify GIT involvement with seven specific scales., Results: Mean FFMI was 16.2 kg/m 2 (IQR 15.2-17.6). The median UCLA total score was 0.53 (IQR 0.19-0.89). FFMI showed a significant negative correlation with UCLA total score (r = -0.29, p = 0.016) and UCLA distention/bloating (r = -0.35, p < 0.01). In 16 patients (23.1%), FFMI was reduced and UCLA distention/bloating was significantly higher (p = 0.039) in SSc patients with lower FFMI [1.75 (IQR 0.75-2.12) vs 0.75 (IQR 0.25-1.75)]. At multiple linear regression model, FFMI showed association with UCLA distention/bloating [beta coefficient - 0.315 (95% CI of beta coefficient: -0.591; -0.039), p = 0.026], BMI [beta coefficient 0.259 (95% CI of beta coefficient: 0.163; 0.355), p = 0.001], and disease duration [beta coefficient - 0.033 (95% CI of beta coefficient: -0.059; -0.007), p = 0.015]., Conclusions: In SSc, low FFMI is associated with symptoms related to GIT involvement, in particular with distension/bloating. Key Points • FFMI is associated with symptoms related to GIT involvement. • Low FFMI is associated with symptoms related to UCLA distention/bloating. • Malnutrition is not associated with symptoms related to GIT involvement., (© 2022. The Author(s).)

Objectives: To describe the use of extracorporeal membrane oxygenation (ECMO) in the management of pediatric poisoning in the United States and to identify predictors of mortality., Design: Retrospective cohort study., Setting: Data reported to the Extracorporeal Life Support Organization by 76 U.S. ECMO centers from 2003 to 2019., Patients: Pediatric patients (0-18 yr) receiving ECMO for poisoning., Interventions: None., Measurements and Main Results: During our study period, 86 cases of acute poisoning were identified and included in the analysis. The median age was 12.0 year and 52.9% were female. The most commonly reported substance exposures were hydrocarbon (n = 17; 19.8%), followed by chemical asphyxiants (n = 14; 16.3%), neuroactive agents (n = 14; 16.3%), opioid/analgesics (n = 13; 15.1%), and cardiovascular agents (n = 12; 14.0%). Single substance exposures were reported in 83.7% of the cases. The intention of the exposure was unknown in 65.1%, self-harm in 20.9% and 10.5% was unintentional exposure. Fifty-six patients (65.1%) survived. Venoarterial ECMO was used more frequently than venovenous ECMO, and its use increased significantly during the study period (p < 0.01). A bimodal distribution of ECMO support was observed among two age groups: less than or equal to 3 years (n = 34) and 13-17 years (n = 41). Hemodynamic and metabolic parameters improved for all patients with ECMO. Persistent systolic hypotension, acidemia/metabolic acidosis, and elevated Pao2) after 24 hours of ECMO support were associated with mortality. Time from PICU admission to ECMO cannulation was not significantly different between survivors (24.0 hr; interquartile range [IQR], 11.0-58.0 hr) and nonsurvivors (30.5 hr; IQR, 10.0-60.2 hr; p = 0.58). ECMO duration and PICU length of stay were significantly longer in survivors than in nonsurvivors (139.5 vs 70.5 hr; p = 0.007 and 25.0 vs 4.0 d; p = 0.002, respectively)., Conclusions: ECMO may improve the hemodynamic and metabolic status of poisoned pediatric patients. Persistent hypotension, acidemia/acidosis, and elevated Pao2 after 24 hours of ECMO were associated with mortality., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Objective: To evaluate the impact of preoperative low-residue diet on intra- and postoperative outcomes among gynecological surgical patients., Methods: This is a surgeon-blind, randomized controlled trial enrolling patients undergoing elective surgery for either benign disease or endometrial carcinoma. Patients were preoperatively randomized to receive either low-residue diet (arm A) or free diet (arm B) starting from three days before surgery. The primary outcome was the quality of the surgical field (scored using a 5-point scale, from poor to excellent). Secondary outcomes were postoperative pain (assessed through VAS scale), postoperative complications, operative time, time to first passage of flatus, length of hospital stay. Perioperative data were collected and compared between groups., Results: A total of 96 patients were enrolled and randomized in arm A (n = 49; 51%) and arm B (n = 47; 49%). The mean age was 47.8 ± 15.6 years in arm A and 48.1 ± 11.3 years in arm B. Endometrial cancer patients were 16.3% in arm A and 10.6% in arm B, and patients with benign disease were 83.7% and 89.4%, respectively. The surgical evaluation of the small intestine was scored < 3 in 2.0% of arm A patients versus 31.9% in arm B (Odds Ratio (OR), 0.04 [95% CI, 0.01-0.35]; p < 0.001), and in 6.1% and 44.7% (OR, 0.08 [95% CI, 0.02-0.30]; p < 0.001), respectively, for large intestine. The mean operative time was 90.4 ± 33.4 min in arm A versus 111.6 ± 37.5 in arm B (Mean Difference (MD): -21.20 [95% CI, -35.43, -6.97]; p = 0.003). The number of patients who reported the time to first flatus within 24 h after surgery was significantly higher in arm A compared with arm B (77.6% vs 44.7%; OR, 4.28 [95% CI, 1.77-10.35]; p = 0.002). No significant differences in terms of postoperative complications, pain, and length of hospital stay were observed between the two groups., Conclusion: Introducing a preoperative low-residue diet could improve the quality of the surgical field and reduce both the operative duration and the time to first passage of flatus among patients undergoing gynecological surgery. Further large-scale studies are required to confirm these findings., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The SARS-CoV-2 spread is a threatening and challenging issue for correctional systems worldwide because of many factors, particularly overcrowding and of the intrinsic characteristics of the population. The prevention measures adopted by the Italian Government were aimed to protect and preserve both inmates' and prison workers' health. The present study aimed to evaluate the efficacy of the adopted strategies., Methods: Data regarding Italian prisons' occupation and prisoners' population from January 2019 to June 2021, as well as the cumulative weekly increase of confirmed cases and the number of doses of vaccine administered among the population of inmates, the prison workers, and Italian population from November 2020 to the end of June 2021, were collected., Results: Prisons' occupation dropped from 120% to 106% after the beginning of the pandemics. The confirmed cases between inmates were consistently lower than among the Italian population and prison workers. A time-series chart showed a time lag of one week between the peaks of the different population., Conclusions: The containing strategies adopted by the Italian correctional system have proved their effectiveness in terms of the prevention and protection of both inmate and staff health.

Objectives: The study aim was to evaluate the estimated glomerular filtration rate (eGFR), its association with clinical disease and its predictive ability with respect to mortality in SSc patients from the European Scleroderma Trials and Research Group (EUSTAR) database., Methods: SSc patients from the EUSTAR database who had items required for the calculation of eGFR at a baseline visit and a second follow-up visit available were included. A cut-off eGFR value of 60 ml/min was chosen for all SSc patients, and 30 ml/min for those with scleroderma renal crisis (SRC). Cox regression and competing risk analysis were performed to evaluate the use of eGFR as a predictive factor of mortality., Results: A total of 3650 SSc patients were included in this study. The median serum level of creatinine and the mean of eGFR were 0.8 mg/dl (interquartile range = 0.6-0.9) and 86.6 ± 23.7 ml/min, respectively. The eGFR was significantly lower in patients with pulmonary hypertension. Overall survival (OS) was significantly reduced in SSc patients with eGFR < 60 ml/min compared with patients with eGFR ≥ 60 ml/min [OS at 5 years 0.763 (95% CI: 0.700, 0.814) vs 0.903 (95% CI: 0.883, 0.919; P < 0.001)]. In multivariable analysis, OS was associated with male gender (P < 0.01), systolic pulmonary arterial pressure (sPAP) (P < 0.001) and eGFR (P < 0.001). The cumulative incidence of deaths due to SSc was associated with increased sPAP (P < 0.001) and reduced eGFR (P < 0.05). The OS at 5 years of 53 SRC patients was not significantly different between SSc patients with eGFR > 30 ml/min and those with eGFR <30 ml/min., Conclusion: eGFR represents a predictive risk factor for overall survival in SSc. The eGFR, however, does not represent a risk factor for death in SRC., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To evaluate the safety and immunogenicity of the Pfizer-BioNTech COVID-19 vaccine in gynecologic oncology patients under chemotherapy., Methods: A prospective cohort study including gynecologic oncology women who were under chemotherapy or had completed it within 6 months at the time of the study. All patients received a two-dose schedule of the Pfizer-BioNTech COVID-19 vaccine. Results were compared with a control group of healthy women vaccinated in the same period., Results: Overall, 44 oncologic patients with a mean age of 61.3 ± 10.7 years were enrolled: 28 (63.6%) had ovarian cancer, 9 (20.4%) endometrial, and 7 (16%) cervical. The IgG antibody titer after 1 month from vaccination was low in 9 (20.5%) patients, moderate in 21 (47.7%), and high in 14 (31.8%). The 3-month titer was null in 2 (4.5%) patients, low in 26 (59.1%), moderate in 13 (29.5%), and high in 3 (6.8%). Patients ≥ 50 years reported lower 1-month ( p = 0.018) and 3-month ( p = 0.004) titers compared with <50 years. Patients with BMI < 30 kg/m 2 had a higher 1-month titer compared with BMI ≥ 30 kg/m 2 ( p = 0.016). Compared with healthy women ( n = 44), oncologic patients showed a lower 3-month titer ( p < 0.001). None of the patients experienced serious adverse effects., Conclusions: The COVID-19 vaccine was safe and immunogenic in gynecologic oncology patients under chemotherapy. Serological monitoring and further vaccine shots should be considered to boost protection.

Objectives: During the lockdown that started in Italy on 10 March 2020 to address the COVID-19 pandemic, aggressive procedures were implemented to prevent SARS-CoV-2 transmission in SARS-CoV-2-negative patients with haematological malignancies. These efforts progressively reduced Klebsiella pneumonia carbapenemase-producing K. pneumoniae (KPC-KP) spread among these patients. Here we evaluated the potential effects of measures against COVID-19 that reduced KPC-KP transmission., Patients and Methods: We analysed KPC-KP spread among 123 patients with haematological malignancies, hospitalized between March and August 2020, who were managed using measures against COVID-19. Their outcomes were compared with those of 80 patients hospitalized during the preceding 4 months (November 2019-February 2020)., Results: During March-August 2020, 15.5% of hospitalized patients were KPC-KP positive, compared with 52.5% in November 2019-February 2020 ( P  <   0.0001); 8% and 27.5% of patients in these two groups were newly KPC-KP positive, respectively ( P  =   0.0003). There were eight new KPC-KP-positive patients during January 2020 and none during June 2020. The weekly rate of hospitalized KPC-KP-positive patients decreased from 50% during March 2020 to 17% during August 2020. Four KPC-KP bloodstream infections (BSIs) were experienced by 123 patients (3%) in March-August 2020, and seven BSIs (one fatal) by 80 patients (8%) in November 2019-February 2020 ( P  =   0.02). Consumption and expense of ceftazidime/avibactam administered to KPC-KP-positive patients significantly decreased in March-August 2020., Conclusions: Aggressive strategies to prevent SARS-CoV-2 transmission were applied to all hospitalized patients, characterized by high levels of KPC-KP endemicity and nosocomial transmission. Such measures prevented SARS-CoV-2 infection acquisition and KPC-KP horizontal transmission. Reduced KPC-KP spread, fewer associated clinical complications and decreased ceftazidime/avibactam consumption represented unexpected 'collateral benefits' of strategies to prevent COVID-19., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)

Background: Topographic memory is the ability to reach various places by recognizing spatial layouts and getting oriented in familiar environments. It involves several different cognitive abilities, in particular executive functions (EF), such as attention, working memory, and planning. Children with attention deficit hyperactivity disorder (ADHD) show impairments in inhibitory control, regulation of attention, planning, and working memory. Aim: The aim of this study was to evaluate the topographic memory in children with ADHD-combined subtype (ADHD-C). Method: Fifteen children (8-10 years) with a diagnosis of ADHD-C (DSM-5) (ADHD-C group) were compared to 15 children with typical development (TD group) of the same age. All children performed Raven's colored progressive matrices (CPM) test to obtain a measure related with cognitive functioning. The walking Corsi test (WalCT), a large-scale version of the Corsi block-tapping test, was used to assess topographic memory in experimental environment. Results: A higher impairment was observed in ADHD-C than TD with significant differences in the WalCT, in particular on the topographic short-term memory (TSTM) task, on the topographic learning (TL) task, and on the repetition number (RN) task during the TL task. Perseverative errors were reported in performing the square-sequence in the WalCT. Zero-order correlations showed a positive correlation between TSTM and auditory attention, and memory of design of NEPSY-II and digit span of WISC-IV. No statistically significant differences were found between the ADHD-C group and TD group in the TL task in the WalCT condition. Conclusion: In ADHD-C, initial topographic learning was compromised whereas the long-term retention of learned topographical material seemed to not be impaired. In particular, these impairments seem to be linked with difficulties in sustained attention, in spatial memory for novel visual materials, in a poor working memory, and in perseverative behaviors., 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., (Copyright © 2021 Faedda, Guariglia, Piccardi, Natalucci, Rossetti, Baglioni, Alunni Fegatelli, Romani, Vigliante and Guidetti.)

Objective: To identify risk and protective factors for mental health symptoms associated with lifestyle changes caused by home confinement in pediatric subjects and in children and adolescents with a neuropsychiatric disorder. Study design: This was a prospective, cross-sectional study conducted from May 10 to May 31, 2020. Two online anonymous surveys were developed: population-based and clinical-based (children with neuropsychiatric disorders). Outcomes included emotional and behavioral symptoms, as assessed by psychometric scales (BPSC, PPSC, PSC, CES-DC and SCARED, respectively), and lifestyle changes during home confinement (i.e., physical activity, screen time, home schooling, reading). Results: The sample included 9,688 pediatric subjects, and 289 children and adolescents with a neuropsychiatric disorder. The presence of siblings was a protective factor in all ages. In pre- and school children: male sex, a diagnosis of autism, residency in highly affected areas, high parental educational level or job loss, and screen time (>2 h/day) were risk factors. Physical activity, home-schooling, reading, talking with other people were protective factors. Residency in highly affected areas, a diagnosis of mood disorder, parental job loss, and screen time, were associated with a worsening of the depressive symptoms, whereas physical activity, talking with other people, playing with parents were protective activities. Screen time was also a risk factor for anxiety symptoms, while physical activity, reading and talking with other people were protective factors. Conclusions: This study identified risk and protective factors for mental health symptoms associated with lifestyle changes caused by COVID-19 home confinement to promote mental well-being in pediatrics during pandemic times., 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., (Copyright © 2021 Oliva, Russo, Gili, Russo, Di Mauro, Spagnoli, Alunni Fegatelli, Romani, Costa, Veraldi and Manti.)

Background: Despite the empirical and clinical relevance of understanding posttraumatic stress disorder (PTSD) heterogeneity in refugees and asylum-seekers, very few studies have examined the manner in which PTSD symptoms manifest in such populations., Aims: This study sought to investigate patterns and predictors of DSM-5 PTSD in a treatment-seeking sample of African refugees., Methods: Participants were 122 African refugees and asylum-seekers living in Italy who completed measures of trauma exposure and PTSD symptoms. Latent class analysis (LCA) was used to identify PTSD symptom profiles, and predictors of class membership were identified via multinomial logistic regression., Results: Among participants, 79.5% had a probable diagnosis of PTSD. Three PTSD classes were identified by LCA: Pervasive (32.0%) with high probabilities of all symptoms, high-Threat (45.9%) with higher probabilities of intrusions and avoidance symptoms, moderate-Avoidance (22.1%) with high probability of thoughts/feelings avoidance. None of the examined variables (legal status, gender, age, education, months spent in Italy, number of traumatic events, employment) significantly predicted class membership with the relevant exception of reception conditions. Specifically, living in large reception centres (over 1,000 people) significantly predicted Pervasive PTSD class membership compared to high/Threat PTSD class and to moderate/Avoidance class., Conclusion: This study provides evidence for distinct patterns of PTSD symptomatology in refugees and asylum seekers. We identified three classes which present both qualitative and quantitative differences in symptoms: Pervasive class, high-Threat class and a new moderate class, characterised by avoidance symptoms. Reception conditions contributed to the emergence of the Pervasive PTSD profile characterised by the symptoms highest severity. These findings highlight that stressors in the post-migration environment, as inadequate reception conditions in large facilities, may have detrimental effect on refugees' mental health. We emphasise the importance for host countries to implement reception models that provide effective protection and integration to this vulnerable population.

Objectives: While the algorithm to diagnose celiac disease (CD) in children with elevated anti-transglutaminase IgA (TGA-IgA) titers (>10 times upper limit of normal, ULN) is well defined, the management of children with low TGA-IgA values represents a clinical challenge. We aimed to identify the diagnostic value of persistently low positive TGA-IgA titers in predicting CD in children., Methods: We retrospectively analyzed children with symptoms or signs of CD, not eligible for a no-biopsy approach. We included children with at least 2 TGA-IgA measurements, endomysial antibody (EMA) assessment and esophagogastroduodenoscopy with biopsies. TGA-IgA values were provided as multiples of ULN. Patients were classified in groups according to median TGA-IgA values: A (TGA-IgA>1 ≤ 5 × ULN; defined as "low-positive"), B (TGA-IgA > 5 < 10 × ULN; "moderate-positive"), and C (controls)., Results: Data of 281 children were analyzed. Of 162 children in group A, CD was diagnosed in 142 (87.7%), whereas normal duodenal mucosa was found in 20. In group B, all 62 children (100%) received a CD diagnosis. Group C included 57 controls. EMA were undetectable in 31 (15%) of mucosal atrophy cases. On the receiver-operating characteristic curve (area under the curve = 0.910), a mean value of 1.7 ULN showed a sensitivity of 81.4% and specificity of 81.8% to predict mucosal damage., Conclusions: Repeated low or moderate TGA-IgA values (<5 ULN or <10 ULN) are good predictors of a CD diagnosis. Symptomatic children with persistently low positive TGA-IgA titers should undergo esophagogastroduodenoscopy regardless of their EMA status., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) and Acinetobacter baumannii (CR-Ab) represent important cause of severe infections in intensive care unit (ICU) patients. N -Acetylcysteine (NAC) is a mucolytic agent with antioxidant and anti-inflammatory properties, showing also in-vitro antibacterial activity. Aim was to evaluate the effect on 30-day mortality of the addition of intravenous NAC to antibiotics in ICU patients with CR-Kp or CR-Ab septic shock. A retrospective, observational case:control study (1:2) in patients with septic shock caused by CR-Kp or CR-Ab hospitalized in two different ICUs was conducted. Cases included patients receiving NAC plus antimicrobials, controls included patients not receiving NAC. Cases and controls were matched for age, SAPS II, causative agent and source of infection. No differences in age, sex, SAPS II score or time to initiate definitive therapy were observed between cases and controls. Pneumonia and bacteremia were the leading infections. Overall, mortality was 48.9% (33.3% vs. 56.7% in cases and controls, p = 0.05). Independent risk factors for mortality were not receiving NAC ( p = 0.002) and CR-Ab ( p = 0.034) whereas therapy with two in-vitro active antibiotics ( p = 0.014) and time to initial definite therapy ( p = 0.026) were protective. NAC plus antibiotics might reduce the 30-day mortality rate in ICU patients with CR-Kp and CR-Ab septic shock.

The name of the author of the original published version of this article was presented incorrectly. The author name "Antonietta Gigantea" should have been presented as "Antonietta Gigante". This has been correctly presented above.

Unilateral condylar hyperplasia (UCH) is a condyle disorder that arises due to osteoblastic hyperactivity, resulting in facial asymmetry, malocclusion and dysfunction. Authors, in this retrospective study, compared "gold standard" manual-segmentation with a "semi-manual one" using 2 kinds of open-source software (Horos and ITK-SNAP; Penn Image Computing and Science Laboratory) to calculate volume of 80 UCH condyles (40 patients). Moreover, volumetric differences between affected condyle and unaffected 1, between males and females, ages, and classification type were also analyzed. Fifteen patients (37.5%) were male and 25 (62.5%) were female. The gender ratio was 5:2, not far from the ratio 2:1 shown in literature. The mean age was 24 (SD 8.6) years; 22.9 (SD 6.6) for males and 24.6 (SD 9.6) for females according with the mean age derived from the Raijmakers et al meta-analysis and the Nitzan et al study. Right side (60%, 24 patients) was more often affected than the left side (40%, 16 patients). The 67.5% (27 patients) were classified as trasversal type, 25% (10 patients) as vertical types and 7.5% (3 patients) as combined. Despite Horos and ITK-SNAP values presenting some differences, the data follows the same tendency. The relationship is stronger for healthy condyles than affected condyles.

In addition to having postural and kinetic tremor of the upper limbs, some patients with essential tremor (ET) may have head tremor as well as cognitive and psychiatric disorders. We aimed to investigate whether the variable clinical presentation in ET patients, including motor and non-motor symptoms, differs in patients with and without head tremor. We consecutively enrolled 70 patients with a diagnosis of ET. Tremor severity was assessed by means of clinical rating scales. Patients also underwent kinematic recordings of postural and kinetic tremor of the upper limbs based on an optoelectronic system. Several neuropsychological tests were also administered. Finally, we adopted the structured interviews for DSM-IV, SCID-I, and SCID-II to investigate psychiatric and personality disorders. ET patients with upper limb tremor plus head tremor exhibited more severe kinetic tremor of the upper limbs and a higher occurrence of axis I psychiatric disorders than ET patients with upper limb tremor only. Cognitive and other motor and psychiatric features did not differ significantly with respect to tremor distribution. The study findings support the hypothesis that body tremor distribution, i.e., the presence of head tremor, influences the variable clinical presentation of ET. The study results support the notion that cases with head tremor may represent a distinct ET subtype, characterized by a prominent cerebellar involvement, and that psychiatric disorders should be considered as a specific manifestation of ET.

The outcome of high-risk myelodysplastic syndrome (MDS) patients treated with 5-azacitidine (5-AZA) in the real-life setting remains largely unknown. We evaluated 110 MDS patients (IPSS intermediate 2/high) treated outside of clinical trials at a single institution between September 2003 and January 2017. Median duration of therapy was 9.5 cycles. The overall survival (OS) of the whole cohort was 66.1% at 1 year and 38.3% at 2 years. No differences in terms of OS were observed with regard to gender (p = 0.622) and age at baseline (< 65 years, 65-75, and > 75 years, p = 0.075). According to the IPSS-R, the very high-risk group had an inferior 2-year OS (17%) compared with intermediate-group patients (64%, p < 0.001). Transfusion independency at baseline was identified as a favorable prognostic factor on 1-year (66.8%) and 2-year OS (43.4%) (p < 0.001). After four cycles, the persistence of bone marrow blasts > 10% identified patients with a worse outcome, with a 2-year OS of 9.4% (p = 0.002). The occurrence of an infection during the first four cycles impacted on the 2-year OS (31.6% vs 58.3% in patients without infections, p = 0.032). Patients receiving at least 24 cycles of the drug have a 5-year OS of 38.2%. This analysis allowed to identify features at baseline or during treatment with 5-AZA associated with a different 2-year OS.

Imatinib, the first BCR/ABL kinase inhibitor approved for the treatment of chronic myeloid leukemia (CML), has changed the long-term outcome of patients affected by this disease. The aim of our analysis was to report, after a median follow-up of 10.2 years (range 5.8-14.8), the long-term outcome, efficacy, and safety of imatinib treatment (frontline and after interferon failure) in a single institution cohort of 459 patients with CML in chronic phase treated outside of clinical trials. The 10-year overall survival of the whole cohort was 77.1%, while the 10-year probability of dying due to CML and other causes was 7.8% and 16%, respectively. The prognostic value of the BCR-ABL1 ratio at 3 months (⩽ 10%) and of complete cytogenetic response and major molecular response at 1 year was confirmed also in the real-life practice. The EUTOS long-term survival score better stratified the baseline risk of dying of CML compared with other risk scores. Two hundred thirty-six (51.4%) patients achieved a deep molecular response during imatinib treatment after a median time of 4.57 years, and 95 (20.6%) had a stable deep molecular response maintained for at least 2 consecutive years. Imatinib was associated with a low rate of serious cardiovascular events and second neoplasia. This 10-year real-life follow-up study shows that imatinib maintains efficacy over time and that long-term administration of imatinib is not associated with notable cumulative or late toxic effects.

Background: Some studies have demonstrated the high impact of headache and migraine in several areas of children and adolescents' life. In recent years, there has been an increase in scientific interest in the relationship between migraine and emotional regulation, investigating the possible consequences of emotional dysregulation on physical and mental health. While some studies have been carried out on the relationship between alexithymia and headache or migraine (especially in adults), no data exist on relationship between Theory of Mind (TOM), metacognition, and alexithymia in children and adolescents with migraine. Methods: Children with diagnosis of migraine without aura (MWoA) (36 males and 34 females) were compared to a healthy control group (31 males and 39 females). The age range was from 8 to 13 years in both groups. All children completed the Alexithymia Questionnaire for Children (AQC) for the assessment of alexithymia levels and the Domain of Social Perception included in the NEPSY-II to evaluate levels of TOM. Metacognitive development was evaluated with Io e La Mia Mente for children aged between 8 and 10 years and with Metacognitions Questionnaire for Children ( MCQ-C ) for children from 11 to 13. Results: There were no differences between children with MWoA and the control group in metacognitive abilities; only in the subscale "Negative Meta Worrying" of MCQ-C girls scored higher than boys, regardless of the group they were part of. Also, in the NEPSY-II subscale there were no statistically significant differences between the two groups. Children with MWoA scored higher in the AQC subscales "Difficulty Identifying Feelings" and "Difficulty Describing Feelings" than controls. Moreover, children between 8 and 10 years statistically differed from older children in "Difficulty Identifying Feelings" and in Total Score. Conclusion: Our data suggest that children with MWoA have no metacognitive and TOM problems compared to a healthy group. The experimental group showed higher traits of alexithymia, confirming what suggested by other studies in the literature. Future research will have to focus on migraine with aura and tension-type headache to evaluate any differences with children with MWoA.

Background: Prediction of difficult mask ventilation (DMV) is as challenging as difficult laryngoscopy. Ultrasound could be a helpful tool in the prediction of these difficulties., Objectives: The purpose of this study was to evaluate the ability of pre-operative ultrasound assessment of neck anatomy in predicting DMV and difficult laryngoscopy in patients undergoing during elective surgery requiring tracheal intubation., Design: Prospective, single blind, observational study., Setting: Operating theatre of a teaching hospital in Italy from April 2018 to July 2018., Patients: A total of 194 patients aged more than 18 years, without neck masses, previous thyroid surgery or tracheotomy undergoing general anaesthesia and tracheal intubation for elective ear, nose and throat-surgery were included in the study., Outcome Measures: Ultrasound distances were recorded with a linear 6 to 13 MHz ultrasound transducer: measurements included the minimum distance from the thyroid isthmus to skin surface, the minimum distance from the hyoid bone to skin surface (DSHB), the minimum distance from skin to anterior commissure of the vocal cords, the minimum distance from skin to trachea at the level of the jugular notch and the distance from skin to epiglottis midway. The degree of DMV and difficult laryngoscopy was quantified., Results: The mean (SD) of DSHB was 0.88 (0.3) cm in the easy mask ventilation group, 1.4 (0.19) cm in DMV group. The mean of DSHB and of the other ultrasound distances increased according to the DMV and difficult laryngoscopy level. The DSHB was correlated with an increase in the risk for DMV (0.61 [IQR 0.5 to 0.69]). DMV groups were associated with a greater ultrasound-measured DSHB., Conclusion: The prospective observational study confirms the relationship between ultrasound assessment of the anterior soft tissues of the neck and difficult laryngoscopy and DMV. DSHB and the other distances extend the available evidence, not only for difficult laryngoscopy but also for DMV., Trial Registration: Clinicaltrials.gov. identified NCT03592758.

Introduction: Cognitive impairment and dementia represent an emerging health problem. Cardiovascular (CV) risk factors contribute to cognitive impairment., Aim: To investigate the effect of vascular calcification on cognitive impairment and dementia, independently of plaque and traditional CV risk factors., Methods: Four hundred and sixty-nine patients (age of 78.6 ± 6.1 years, 74.4% women) were studied. Traditional CV risk factors levels, cognitive function (MMSE), brain CT scan, and other vascular parameters were measured. Common Carotid Artery (CCA) plaque and calcification were evaluated by ultrasound., Results: CCA calcification was associated with a lower MMSE score than in subjects with no CCA calcification (23.7 ± 0.3 versus 25.5 ± 0.8; p = 0.015), after controlling for age, sex, education, blood pressure levels, diabetes, creatinine, lipid lowering therapy, neuroimaging alteration, and CCA plaque. Similarly, CCA calcification was associated with higher odds of dementia regardless of the presence of CCA plaque (OR 1.70, 95% CI 1.01-2.94, p < 0.05). This trend was not observed when stratifying patients according to the presence of CCA plaque., Conclusion: CCA calcification is associated with cognitive impairment and dementia, independently of established CV risk factors and CCA plaque. The impact of arterial calcification on cognition seems largely independent of arterial stiffness.