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Funding Acknowledgements Type of funding sources: None. Background There is limited knowledge on the incidence of blood stream infections (BSI) in patients with implantable cardioverter defibrillators (ICDs) or cardiac resynchronization therapy devices (CRTs), as well as about the diagnostic work-up and outcome when these patients are admitted to non-cardiology units. Purpose We assessed the incidence of BSI in patients with an ICD or CRT, evaluated the diagnostic work-up performed, and investigated the outcome. Methods This is a single-center, retrospective cohort analysis of all 515 patients implanted with a de-novo ICD or CRT between 2012 and 2021 at our centre, and subsequently admitted to a non-cardiology unit of any public hospital in Canton Ticino with a BSI (≥ 2 positive blood cultures). Device infection was defined according to the 2019 International Cardiac Implantable Electronic Device (CIED) Infection Criteria. Results A total of 43 patients were diagnosed with BSI during a median follow-up of 48 months (IQR 24-78 months). Incidence rate for BSI was 19 (95%-CI 14 – 26) and 23 (95%-CI 14 – 35) per 1000 patient-years for ICDs and CRTs, respectively. The most common source for BSI was urinary tract infection (21%), which was mostly caused by gram positive pathogens (68%) with coagulase-negative staphylococci being the most frequent one (39%). Definite CIED infection rate in patients presenting with BSI was 11.6% (see table). The majority of patients (56%) had no cardiac imaging including transthoracic or transesophageal echocardiography; a PET-CT was performed in only 4 patients (9%). Nearly all patients (86%) were treated with short-term antibiotics; in contrast, system extraction (2.3%) and chronic antibiotic therapy (4.7%) were rarely performed. Throughout the entire follow-up period, patients with BSI had a 8-fold higher probability (HR 7.8, 95% CI 4.8-12.7; p Conclusions Awareness in non-cardiology units about possible device infection in patients with BSI is rather low leading to limited diagnostic work-up and ultimately to a high mortality rate of these patients.

Funding Acknowledgements Type of funding sources: None. Introduction Diagnosis of Brugada Syndrome (BrS) is established either by a observing a spontaneous Type 1 Brugada pattern on ECG or by unmasking Type 1 pattern with a drug challenge using a sodium channel blocker in suspected individuals. There are no clear indications on when to apply the Ajmaline provocation test and how to manage positive case. Data regarding the long-term outcome of this population is limited. The present study was designed to evaluate the incidence and identify predictors of arrhythmic events among subjects with Ajmaline induced Brugada ECG. Objectives To evaluate the long-term outcomes of subjects diagnosed with drug induced Brugada ECG. Methods A multicenter international consecutive cohort including all cases of positive Ajmaline provocation test from 5 large electrophysiology centers form Israel, France, and Switzerland Results A total of 130 patients were recruited, the majority were males (70.8%) and Caucasian (97.7%). In our cohort the most frequent indication for performing an ajmaline test was a family history of BrS or sudden cardiac death (43.1%), then a suspicious ECG (38.5%), syncope (16.1%) and 3 with ventricular fibrillation (VF) (2.3%). The common infusion protocols used were 1mg/kg over 5 minutes (56%) and 1mg/kg over 10 minutes (26%). In all centers ajmaline infusion was stopped when type 1 Brugada pattern was observed. No adverse events occurred during the studies. All patients received instructions regarding the avoidance of arrhythmic triggers (specific drugs, alcohol and reduction of fever). During a median follow up time of 36 (7.5-66.9) months, 9 syncope occurred, 15 ICD (3 for secondary prevention because of VF as initial presentation) and 29 ILRs were implanted. No VF or deaths occurred in any of the study groups. Conclusion In the present study of consecutive patients with a positive Ajmaline provocation test, there were no adverse outcomes during a median follow up of 3 years, irrespective of the indication for the test. Our results, indicating a low risk, are in agreement with the current ESC guidelines limiting the diagnosis of Brugada syndrome. Further research is warranted to test whether these patients maybe be managed safely solely by education to avoid arrhythmic triggers.

Background Cardiac resynchronization therapy (CRT) is clinically proven in patients with heart failure (HF) and left bundle branch block (LBBB). However, approximately 30% of CRT individuals are non responsive to the therapy while factors affecting electromechanical coupling remain not fully understood. Objective To determine the optimal combination of electromechanical parameters associated with responsiveness to CRT. Methods Sixty-two patients with HF/LBBB underwent invasive anatomo-electromechanical mapping (AEMM) of the left ventricle using NOGA XP system (Biosense Webster), cardiac magnetic resonance (cMR), transthoracic echocardiography and 12-lead ECG. Remodeling was quantified based on the end-systolic volume (ΔESV) decrease at 6-month follow-up. Response to CRT was defined as ΔESV ≤−15%. QRS duration (QRSd) was measured from a surface ECG. Area strain was obtained from AEMM and used to calculate systolic stretch index (SSI) and total left ventricular mechanical time (TLVMT). Total left ventricular activation time (TLVAT) and transeptal time (TST) were derived from AEMM and ECG. Scar burden was evaluated from cMR late gadolinium enhancement imaging. Results Significant correlations were observed between ΔESV and TST (rho=0.42; responder: 50 [20–58] vs non-responder: 33 [8–44] ms), TLVAT (−0.68; 81 [73–97] vs 112 [96–127] ms), scar burden (−0.27; 0.0 [0.0–1.2] vs 8.7 [0.0 19.1]%) and SSI (0.41; 10.7 [7.1–16.8] vs 4.2 [2.9–5.5]), but not QRSd (0.11; 155 [140–176] vs 167 [155–177] ms). TLVAT and SSI had a high predictive value for CRT response (AUC>0.80). TLVAT (OR=1.50), scar burden (0.91) and SSI (0.04) were independent factors associated with a positive response to CRT. Individuals with SSI >7.9% and TLVAT Conclusion Electromechanical parameters show better correlation with CRT response than traditional surface ECG measurements. The absence of scar combined with high SSI and low TLVAT ensures effectiveness of CRT. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Swiss National Science Foundation, Statutory funds of the Medical University of Silesia

Background Anterior cervical discectomy and fusion (ACDF) has conventionally been performed using an allograft cage with a plate-and-screw construct. Recently, standalone cages have gained popularity due to theorized decreases in operative time and postoperative dysphagia. Few studies have compared these outcomes. Here, we directly compare the outcomes of plated versus standalone ACDF constructs. Methods A single-center retrospective review of patients undergoing ACDF after June 2011 with at least 6 months of follow up was conducted. Clinical outcomes were analyzed and compared between standalone and plated constructs. Multivariate regression analysis of the primary outcome, need for revision surgery, as well as several secondary outcomes, procedure duration, estimated blood loss (EBL), length of hospital stay, disposition, and incidence of dysphagia, hoarseness, or surgical site infection, was completed. Results A total of 321 patients underwent ACDF and met inclusion-exclusion criteria, with mean follow-up duration of 20 months. Forty-six (14.3%) patients received standalone constructs, while 275 (85.7%) received plated constructs. Fourteen (4.4%) total revisions were necessary, 4 in the standalone group and 10 in the plated group, yielding revision rates of 8.7% and 3.6%, respectively (P = .125). Mean EBL was 98 mL in the standalone group and 63 mL in the plated group (P = .001). Mean procedure duration was 147 minutes in the standalone group and 151 minutes in the plated group (P = .800). Mean hospital stay was 3.6 days in the standalone group and 2.5 days in the plated group (P = .270). There was no significant difference in incidence of dysphagia (P = .700) or hoarseness (P = .700). Conclusions Standalone ACDF demonstrates higher, but not statistically significant, revision rates than plate-and-screw constructs, without the hypothesized decreased incidence of dysphagia or hoarseness and without decreased procedure duration or EBL. Surgeons may consider limiting use of these constructs to cases of adjacent segment disease. Larger studies with longer follow up are necessary to make more definitive conclusions. Level of Evidence 4. Clinical Relevance This study will help spine surgeons decide between using standalone or cage-and-plate constructs for ACDF.

Humanin (HN) is a short peptide involved in many biological processes such as apoptosis, cell survival, inflammatory response, and reaction to stressors like oxidative stress, between others. In the ovary, a correct balance between pro- and anti-apoptotic factors is crucial for folliculogenesis. In the follicular atresia, survival or death of granulosa cells is a critical process. The goal of this study was to evaluate the action of HN on granulosa cell fate. To explore endogenous HN function in the ovary, we used a recombinant baculovirus (BV) encoding a short-hairpin RNA targeted to silence HN (shHN). HN downregulation modified ovarian histoarchitecture and increased apoptosis of granulosa cells. HN was also detected in a granulosa tumor cell line (KGN). Transduction of KGN cells with BV-shHN resulted in HN downregulation and increased apoptosis. On the other hand, treatment of KGN cells with exogenous HN increased cell viability and decreased apoptosis. In summary, these findings indicate that HN is a cytoprotective factor in granulosa cells of antral follicles, suggesting that this peptide would be involved in the regulation of folliculogenesis. Also, this peptide is a cytoprotective factor in KGN cells, and therefore, it could be involved in granulosa tumor cell behavior.

Gilles de la Tourette syndrome is a multifaceted neurodevelopmental disorder characterized by multiple motor and vocal tics. Research in Tourette syndrome has traditionally focused on the motor system. However, there is increasing evidence that perceptual and cognitive processes play a crucial role as well. Against this background it has been reasoned that processes linking perception and action might be particularly affected in these patients with the strength of perception-action binding being increased. However, this has not yet been studied experimentally. Here, we investigated adult Tourette patients within the framework of the ‘Theory of Event Coding’ using an experimental approach allowing us to directly test the strength of perception-action binding. We included 24 adult patients with Tourette syndrome and n = 24 healthy control subjects using a previously established visual-motor event file task with four levels of feature overlap requiring repeating or alternating responses. Concomitant to behavioural testing, EEG was recorded and analysed using temporal signal decomposition and source localization methods. On a behavioural level, perception-action binding was increased in Tourette patients. Tic frequency correlated with performance in conditions where unbinding processes of previously established perception-action bindings were required with higher tic frequency being associated with stronger perception-action binding. This suggests that perception-action binding is intimately related to the occurrence of tics. Analysis of EEG data showed that behavioural changes cannot be explained based on simple perceptual or motor processes. Instead, cognitive processes linking perception to action in inferior parietal cortices are crucial. Our findings suggest that motor or sensory processes alone are less relevant for the understanding of Tourette syndrome than cognitive processes engaged in linking and restructuring of perception-action association. A broader cognitive framework encompassing perception and action appears well suited to opening new routes for the understanding of Tourette syndrome.

Funding Acknowledgements Type of funding sources: None. Background Leadless pacing has been established as an alternative approach to transvenous devices for selected patients suffering from bradycardias. While in the majority of cases leadless pacemaker implantation represents a de novo procedure, in an increasing number of patients such a device is used after a previously implanted transvenous pacemaker. Purpose Retrospective analysis of the efficacy and safety outcome in patients who underwent leadless pacemaker implantation in the context of a previously implanted conventional pacemaker. Methods and Results In this retrospective analysis from two large Swiss implantation centres, 257 consecutive patients undergoing leadless pacemaker implantation were included. Of the total cohort, 233 patients were diagnosed with new-onset bradycardias, while in 24 patients a prior transvenous device was present. Out of these 24 patients, 20 subjects required lead extraction of the previous system due to infection (70%, 14 patients), malfunction or other reasons (Table 1). In 3 patients with device-related infection, lead extraction and leadless pacemaker implantation were performed as a single procedure, while in the remaining 11 cases a time window between the two procedures was present (median of 11.5 days with a range of 2 to 186 days). In the population with a previous device, mean age at implantation was 81 ± 9 years which did not differ compared to the de novo cohort. Mean implantation duration was 57 ± 31 minutes in the cohort with a previous device versus 48 ± 191 minutes in the de novo population without a significant difference (P=NS) and with a successful implantation rate of 100% versus 98.7% in the de novo population (P=NS). Electrical device parameters (sensing, impedance, threshold) at implantation and during follow-up (mean 12.5 ± 9.3 months) were similar between the two groups. Eight major periprocedural complications (3.1%) were encountered (4 pericardial effusions, 3 femoral bleedings and 1 intra-abdominal bleeding) in the entire cohort within a 30 days period, of which the majority occurred in the de novo cohort (75 %, 6 of 8). A total of 4 pericardial effusions occurred, which could be managed without the need for cardiac surgery. The were no reinfections registered after leadless pacemaker implantation during follow-up. Conclusions Implantation of a leadless pacemaker in patients with a prior conventional system (with or without extraction of the previous device) was effective and safe in our population of patients.

Funding Acknowledgements Type of funding sources: None. Background Left bundle branch block (LBBB) is common after transcatheter aortic valve implantation (TAVI) and is an indicator of subsequent high-grade atrioventricular block. Consensus regarding a reasonable strategy to manage cardiac conduction disturbances after TAVI has been elusive Methods The European Heart Rhythm Association (EHRA) conducted a survey to capture contemporary clinical practice for conduction disorders after TAVI. A 25-item online questionnaire was developed and distributed among the EHRA electrophysiology research network centres. Results Of 117 respondents, 44% were affiliated with university hospitals. This survey has revealed that a standardized management protocol for advanced conduction disorders such as LBBB or AVB after TAVR is available in 63% of participating centres. Telemetry was chosen by most participants as the most frequent management strategy for patients with new or preexisting LBBB after TAVI (79%, 70%, respectively, Figure 1). Duration of telemetry in patients with new LBBB varied: 18% chose 24 hours, 35% 48 hours, 27% 72 hours and 20% ≥ 72 hours. Similarly, in patients with new LBBB after TAVI undergoing EP study, the cut-off for a prolonged HV interval for PM implantation was heterogenous among European centers (7.4% ≥ 55ms and 44% ≥ 75ms). Conduction system pacing was chosen as preferred device therapy in patients with LBBB and normal LVEF in 3.7% and in patients with LBBB and reduced LVEF in 5.6%. Conclusions The management of conduction disorders after TAVI is very heterogeneous across European centres. Risk stratification strategies vary substantially. The role of conduction system pacing in patients with LBBB after TAVI needs to be defined. There is a considerable room for better uniformity in clinical practice.

Funding Acknowledgements Type of funding sources: None. Background Impairment of the conduction system may occur in 9-30 % of patients undergoing transcatheter aortic valve replacement (TAVR). Since this is typically an elderly and frail patient population, leadless pacing potentially offers benefits over conventional transvenous pacemaker devices. However, available efficacy and safety outcome data of leadless pacing in a population who underwent a TAVR procedure is still limited. Purpose Retrospective analysis of efficacy and safety outcome data in patients who underwent leadless pacemaker implantation after TAVR due to relevant bradycardias. Methods and Results In this retrospective analysis from two large Swiss implantation centres, 257 consecutive patients undergoing leadless pacemaker were included. Of the total cohort, 26 subjects had a previous TAVR complicated by early (within 30 days)- or late-onset (after 30 days) bradycardias (Table 1). The TAVR group did not differ compared to the non-TAVR with regard to age, gender and left-ventricular ejection fraction (LVEF). Median duration between valve intervention and leadless pacemaker implantation was 8 days (range 0 to 368 days). After a TAVR procedure, left femoral access was chosen in 30.8% (8 of 26 of cases) for the leadless pacemaker implantation as compared to 5.2% (12 of 231 of the cases) in the remaining population (P < 0.01). Mean implantation duration was 56 ± 22 min in the TAVR group compared to 48 ± 20 min (P = NS) and a successful implantation rate of 100.0 % in the TAVR group vs 98.7% in the remaining population (P = NS). There were no significant differences in pacing parameters (sensing, impedance and threshold, respectively) between the two groups. A total of eight major periprocedural complications (3.1%) were encountered in the entire cohort within 30 days, of which one (pericardial effusion) occurred in the TAVR population (P = 0.04), which was managed conservatively with pericardiocentesis. Conclusions Leadless pacemaker implantation appears to be safe and effective in patients after TAVR in need of antibradycardia pacing.

Elusive features in photonic and electronic devices can be detected by means of advanced, time-domain spectroscopic techniques. In this letter we introduce a novel kind of modulation spectroscopy, based on the optomechanical interaction of photonic and mechanical modes. Applying the technique to a Si metasurface and its drum-like mechanical modes, we detect narrow-band quasi-Bound-State-in-the-Continuum (q-BIC) modes close to normal incidence, where their measurement can be hindered by a high symmetry protection and undesired background modes. Showing a visibility enhancement of more than one order of magnitude, the optomechanical modulation spectroscopy can be an innovative tool for precise spectroscopy of a wide set of photonic devices, including the goal of measuring purely symmetry protected BIC resonances., 7 pages, 4 figures

This paper discusses an environmentally-friendly destination for the residual ashes resulting from the firing of biomass (wood wastes) at the Engie Brasil Cogeneration Power Plant located in Lages, Santa Catarina, Brazil. The study proposes reusing the residue as a substitution for crushed stones in the production of concrete. Environmental, physical, and chemical analyses were performed for characterization of the ashes. Specimens prepared with ash and subjected to testing presented a compressive strength of around 18.63 Mpa (2700 psi), which is in compliance with the ACI-213R and ASTM C330-5 specifications. With pretreatment and proper mixing ratios, biomass ashes may be employed as an aggregate in the manufacture of lightweight structural concrete.

The disturbance decoupling problem is considered in the framework of switching linear systems assuming that no information on the actual value of the switching signal or on the current mode of the system is available. By introducing the novel notion of strong conditioned invariant subspace, the solvability of the problem is completely characterized by means of necessary and sufficient conditions. Constructive procedures to check the solvability conditions and to construct solutions, if any exists, are given.

Despite the negative impact of cigarette smoking on oral health and teeth appearance, there is no data available on dental shade changes in smokers who quit smoking. Dental discoloration caused by smoking may be permanent, with minimal restoration after stopping smoking. If this is valid, former smokers can show dental shade values equivalent to those of current smokers.The aim of this study is to compare the dental shade assessment by digital spectrophotometry (VITA Easyshade V) in current, former and never smokers and to verify the short (7 days) and long-term (30 days) repeatability of these measurements.Confirmation of good reproducibility of VITA Easyshade V with clear objective discrimination of dental shade measurements among current, former, and never smokers will improve the power of this measurement giving more confidence in clinical research findings of dental shades in these populations.It is also anticipated that results from the study will expand the application of this measurements to include medical and regulatory research applied to combustion-free tobacco products (e.g. e-cigarettes, heated tobacco products, oral tobacco/nicotine products, etc.), smoking cessation medications, and to consumer care product for oral hygiene and dental aesthetics.

Although the detrimental health effects of smoking on human health are well described, the impact of smoking on dental plaque build-up lacks consistent records. This is because dental research on periodontal health has primarily relied on subjective indices with poor discriminatory power. Novel digital imaging techniques for the objective quantitation of dental plaque are now available. Quantitative Light-Induced Fluorescence (QLF) technology has been used in several studies for digital quantification and monitoring of dental plaque.The objective of the study is to quantitate and compare short- and long-term repeatability of dental plaque among current, former, and never smokers by using a high resolution, auto-focus, hand-held QLF scanner (QRayCam™ Pro; Inspektor Research Systems BV, Amsterdam, NL).Demonstration of good reproducibility of QLF technology with clear discrimination for dental plaque quantitation among current, former, and never smokers will pave the way to future application of this test for both medical and regulatory research applied not only to combustion-free tobacco products (e.g. e-cigarettes, heated tobacco products, oral tobacco/nicotine products, etc.) and smoking cessation medications, but also to consume care product for oral hygiene.

Tourette syndrome (TS) and obsessive–compulsive disorder (OCD) are two neurodevelopmental disorders characterized by repetitive behaviors. Our recent study in drug-naive children with TS and OCD provided evidence of cerebellar involvement in both disorders. In addition, cerebellar functional connectivity (FC) was similar in TS patients without comorbidities (TSpure) and TS patients with OCD comorbidity (TS + OCD), but differed in pure OCD patients. To investigate in detail the cerebellar involvement in the pathophysiology of TS and OCD, we explored cerebellar structural and functional abnormalities in drug-naive children with TSpure, TS + OCD, and OCD and assessed possible correlations with severity scores. We examined 53 drug-naive children, classified as TSpure (n = 16), TS + OCD (n = 14), OCD (n = 11), or controls (n = 12). All subjects underwent a multimodal 3T magnetic resonance imaging examination. Cerebellar lobular volumes and quantitative diffusion tensor imaging parameters of cerebellar peduncles were used as measures of structural integrity. The dentate nucleus was selected as a region of interest to examine cerebello-cerebral functional connectivity alterations. Structural analysis revealed that both TSpure and TS + OCD patients had higher fractional anisotropy in cerebellar peduncles than controls. Conversely, OCD patients were characterized by lower fractional anisotropy than both controls and TSpure and TS + OCD patients. Lastly, cerebellar functional connectivity analysis revealed significant alterations in the cerebello-thalamo-cortical circuit in TSpure, TS + OCD, and OCD patients. Early cerebellar structural and functional changes in drug-naive pediatric TSpure, TS + OCD, and OCD patients support a primary role of the cerebellum in the pathophysiology of these disorders.

Highlights • Feature Binding/integration in the motor domain in Tourette Syndrome (TS) is examined. • Motor binding processes and interleaved action are intact in TS. • Binding processes are differentially modulated in the motor domain and sensori-motor processes., Because tics are the defining clinical feature of Tourette syndrome, it is conceptualized predominantly as a motor disorder. There is some evidence though suggesting that the neural basis of Tourette syndrome is related to perception–action processing and binding between perception and action. However, binding processes have not been examined in the motor domain in these patients. If it is particularly perception–action binding but not binding processes within the motor system, this would further corroborate that Tourette syndrome it is not predominantly, or solely, a motor disorder. Here, we studied N = 22 Tourette patients and N = 24 healthy controls using an established action coding paradigm derived from the Theory of Event Coding framework and concomitant EEG-recording addressing binding between a planned but postponed, and an interleaved immediate reaction with different levels of overlap of action elements. Behavioral performance during interleaved action coding was normal in Tourette syndrome. Response locked lateralized readiness potentials reflecting processes related to motor execution were larger in Tourette syndrome, but only in simple conditions. However, pre-motor processes including response preparation and configuration reflected by stimulus-locked lateralized readiness potentials were normal. This was supported by a Bayesian data analysis providing evidence for the null hypothesis. The finding that processes integrating different action-related elements prior to motor execution are normal in Tourette syndrome suggests that Tourette it is not solely a motor disorder. Considering other recent evidence, the data show that changes in “binding” in Tourette syndrome are specific for perception–action integration but not for action coding.

Although the well-known detrimental effects of conventional cigarette smoking on oral health, there are still lack of evidences about the impact of less harmful alternatives (such as electronic cigarettes or heat not burn products), especially in young smokers with clinical absence of signs of periodontitis.SMILE will be a prospective, multicenter, interventional, open label, randomized, controlled, three parallel-arms study assessing oral health parameters and teeth appearance of 18 months duration.This study aims to compare short- and long-term impact on oral health between smokers continuing with conventional cigarette smoking, those switching to combustion-free nicotine delivery systems (C-F NDS), and never-smokers by objectively evaluating changes in gingival response, as a proxy for periodontal/gingival.The total number of participants in the study planned of the trial is 606 (505 regular smokers and 101 never-smokers).Regular smokers not intending to quit will be randomized in the ratio 1:4 either in continuing to smoke commercially manufactured conventional cigarettes (n = 101; Study Arm A) or switching to C-F NDS (n = 404; Study Arm B), never-smokers will be assigned in Arm C (n= 101).The primary outcome will be to assess and compare the percentage mean change in Modified Gingival Index (MGI) score between Baseline and 18 months follow-up between the Study Arms A and B.Secondary outcomes include the assessment of within- and between-group (Arm A, Arm B and Arm C) variations from baseline to 18 months follow-up of several endpoints, such as MGI, Tooth Stains Assessment, Dental Discolorations, Plaque Score Imaging, Oral Health Quality of Life (OHQOL) assessment and EuroQoL Visual Analog Scale (EQ VAS – QoL) assessment.Patient recruitment will start in January 2021 and enrolment is expected to be completed by June 2021.This will be the first study determining overall oral health impact of using CF-NDS in smokers without sign of periodontitis. Data from this study will provide valuable insights into the overall potential of C-F NDS to reduce the risk of periodontal diseases.

During the early stages of the coronavirus disease 2019 (COVID-19) pandemic in Italy, an online survey was launched via a local patient advocacy website to investigate mental health issues in children and adolescents with Tourette syndrome (TS). Respondents were parents, who were asked to report on their child's general health, tics, comorbidities/problems, pharmacological treatment/psychotherapy, symptom variations, and daily routine, as well as on their family's health and work experiences during the pandemic. Two hundred thirty-eight people participated in the survey, 203 females and 35 males. Our findings indicate that, in the time window of 4–6 weeks after the beginning of the COVID-19-related lockdown, 67% of individuals with TS developed a relevant worsening of the overall clinical condition as rated by their parents. An improvement or no variation of the clinical picture was reported in 20.5 and 6.7% of cases, respectively. Most worsened symptoms included tics, hyperactivity, rage attacks, obsessions/compulsions, and anxiety. Of the subjects experiencing a clinical worsening, the majority (51.76%) showed variations across two to five symptom domains. No association was found between symptom variation and family demographics or health and economic issues specifically related to the lockdown. The current COVID-19 pandemic is exerting a considerable impact on the mental health of young individuals with TS by worsening both tics and emotional and behavioral symptoms.

Tobacco smoking impairs mucociliary clearance (MCC) efficiency as shown by prolonged saccharin test transit time (STTT). Avoiding exposure to tobacco smoke from combustible cigarettes may restore MCC function and former smokers have been shown to exhibit similar STTT as never smokers. The impact of switching from smoking to combustion-free tobacco products such as e-cigarettes (ECs) and heated tobacco products (HTPs) on STTT is not known. We report STTT of exclusive EC and HTP users. Test results were compared to those obtained in current, former, and never smokers.STTT were obtained from 39 current, 40 former, 40 never smokers and from 20 EC and 20 HTP users. Comparison of STTT values showed significant difference among the five study groups (p< 0.00001) with current smokers having a median (IQR) STTT of 13.15 min, which was significantly longer compared to that of all other study groups. In particular, compared to former (7.26 min) and never smokers (7.24 min), exclusive EC users and exclusive HTP users had similar STTT at 7.00 and 8.00 min respectively.Ex-smokers who have switched to exclusive regular use of combustion-free nicotine delivery systems (i.e. ECs and HTPs) exhibit similar saccharin transit time as never and former smokers. This suggests that combustion-free nicotine delivery technologies are unlikely to have detrimental effects on MCC function.

Highlights • Intracranial hemorrhage occurs in COVID-19 patients with prolonged hospitalization. • SARS-CoV-2 binds to the endothelial lining of the cerebral vasculature via ACE-II. • Direct endothelial injury, pro-thrombotic states and DIC lead to hemorrhagic events. • We advocate heightened vigilance for intracerebral hemorrhage in COVID-19 patients., In this study, we report three cases of spontaneous intracranial hemorrhage in patients who were initially hospitalized at our tertiary care center in Washington, DC with symptoms of COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was diagnosed in all three patients, who were critically ill, requiring intubation and ventilatory support. During their protracted hospitalizations, subsequent imaging disclosed intracranial hemorrhages, including intracerebral and subarachnoid hemorrhages, in the context of anticoagulation and coagulopathy. We believe this is related to the tropism of SARS-CoV-2 to the endothelial lining of the cerebral vasculature via their angiotensin-converting enzyme (ACE) II receptors. Given our findings, we advocate heightened vigilance for intracerebral hemorrhage events, and scanning when practicable, in COVID-19 patients which have prolonged ventilatory support and depressed neurologic examinations.