Infectious risk in multiple sclerosis patients treated with disease-modifying therapies: A three-year observational cohort study

Background The disease-modifying therapies (DMTs) largely used in multiple sclerosis (MS) may result in higher infectious risk. Objective We aimed to investigate the infectious risk in DMT-treated MS patients. Methods MS patients were evaluated for infectious risk before starting, switching or during DMT. Results In this three-year observational cohort study 174 MS patients were enrolled. Among them, 18 patients were anti-HBc + and 19 patients were QuantiFERON®-TB Gold In-Tube (QFT) + . No patients with anti-HBc + showed a detectable HBV-DNA and all started DMT. Among QTB + patients, 17 latent TB infections (LTBIs) and 2 active TB infections (TBIs) were identified. After one month of LTBI prophylaxis or TB treatment, respectively, all patients started DMTs. Overall, 149 started DMTs. During DMTs, one ocrelizumab-treated patient with anti-HBc + developed HBV reactivation and six patients (3 on natalizumab, 2 on ocrelizumab and 1 on IFN-β) showed reactivation of HSV-1, with detectable plasma DNA. Finally, 1 cladribine-treated patient experienced VZV reactivation. All the reactivations of latent infections have been successfully treated. Conclusion Screening of infectious diseases in DMT candidate MS patients helps to mitigate the infectious risk. During DMTs, a regular assessment of infectious risk allows to avoid discontinuing MS therapy and guarantees a higher degree of safety.

598 Are risk scores sufficient to stratify patients undergoing lead extraction? A single-centre analysis

Aims Device implantation is growing exponentially, as well as associated infections, ranging from isolated pocket erosion to endocarditis and bacteraemia, all worsening the prognosis of patients with frailty and comorbidity. Transvenous lead extraction (TLE) can resolve the complications, although a 1-year mortality risk of up to 25% is reported; despite higher health costs, prolonged hospitalization, and poor quality of life, strategies for predicting increased infection risk and reduced infection incidence are yet missing. Currently applied clinical scores do not consider etiologic microbial agents. We aimed to assess whether PADIT and UPCM scores could be implemented when bacteria or fungi are known to be causative of infection, and how these agents affected the outcome. Methods and results A retrospective analysis of patients undergone cardiac implantable electronic device (CIED) pocket revision, and/or TLE between 2016 and 2021 was performed. For each procedure, microbiological samples of both generator pocket tissue and intracardiac portions of the leads were analysed. In addition, blood cultures were performed in three sets. Transesophageal echocardiography was performed in all cases for ruling out suspected endocarditis. Spearman ad Pearson coefficients were tested for correlation among microorganism, prior infection and/or procedure, PADIT and UPCM scores; a P-value less than 0.05 was considered significant. We analysed 14 patients (10 males, 4 females, mean age ± SD: 72 ± 13): one case (4%) affected by pocket erosion, seven cases (50%) affected by both pocket site and lead infection (with associated bacteraemia in one subject), and one case (4%) due to lead-related infective endocarditis. Of these, five (36%) underwent device replacement, while nine (64%) to extraction or pocket/lead revision. Nine (64%) patients had positive culture examinations (Figure 1). The correlation method gave a statistically significant association between Gram- infection and prior sepsis (r 0.63; P-value 0.02). We considered the number of procedures on the same pocket and/or CIED previous infections as markers of frailty and increased infectious risk. As expected, the PADIT score, but not UPCM, significantly correlated with the number of previous procedures (r 0.70; P-value 0.006). Indeed, both scores had a similar infectious risk prediction. Conclusions In our analysis, predictive PADIT score of infectious risk performed better than UPCM, while both proved their reliability in identifying high-risk patients. The absence of correlation between UPCM score and infective agents is not conclusive, but probably due to the small sample size. Interestingly, growing rate of device reinfection correlates with the risk of Gram- bacterial infection. Thus, the integration of the microbiological data in the current prediction models could significantly increase their performance.

Implementation of a fully remote randomized clinical trial with cardiac monitoring

Background The coronavirus disease 2019 (COVID-19) pandemic has challenged researchers performing clinical trials to develop innovative approaches to mitigate infectious risk while maintaining rigorous safety monitoring. Methods In this report we describe the implementation of a novel exclusively remote randomized clinical trial (ClinicalTrials.gov NCT04354428) of hydroxychloroquine and azithromycin for the treatment of the SARS-CoV-2–mediated COVID-19 disease which included cardiovascular safety monitoring. All study activities were conducted remotely. Self-collected vital signs (temperature, respiratory rate, heart rate, and oxygen saturation) and electrocardiographic (ECG) measurements were transmitted digitally to investigators while mid-nasal swabs for SARS-CoV-2 testing were shipped. ECG collection relied on a consumer device (KardiaMobile 6L, AliveCor Inc.) that recorded and transmitted six-lead ECGs via participants’ internet-enabled devices to a central core laboratory, which measured and reported QTc intervals that were then used to monitor safety. Results Two hundred and thirty-one participants uploaded 3245 ECGs. Mean daily adherence to the ECG protocol was 85.2% and was similar to the survey and mid-nasal swab elements of the study. Adherence rates did not differ by age or sex assigned at birth and were high across all reported race and ethnicities. QTc prolongation meeting criteria for an adverse event occurred in 28 (12.1%) participants, with 2 occurring in the placebo group, 19 in the hydroxychloroquine group, and 7 in the hydroxychloroquine + azithromycin group. Conclusions Our report demonstrates that digital health technologies can be leveraged to conduct rigorous, safe, and entirely remote clinical trials.

Role of Partial Splenectomy in Hematologic Childhood Disorders

The spleen is a secondary lymphoid organ that belongs to the reticular-endothelial system, directly connected to blood circulation. The spleen is greatly involved in the immune response, especially against capsulated bacteria. Splenectomy plays a fundamental role in the treatment of numerous pediatric hematologic disorders. Taking into account all the possible complications (especially infections) linked to this procedure, alternatives to total splenectomy have been sought. Partial splenectomy has been proposed as a treatment that allows the reduction of infectious risk. This approach has proven safe and feasible in most patients, but multicentric and prospective studies are necessary to more accurately define the indications for performing partial splenectomy. However, vaccinations and antibiotic prophylaxis remain fundamental for preventing serious infections, even in the case of partial splenectomy. We review anatomical and functional properties of the spleen, with a focus on medical or surgical indications to splenectomy, aiming to give practical educational information to patients and their families after splenectomy. Furthermore, we discuss the feasibility of partial splenectomy in children with hematologic diseases who require splenectomy.

The Role of Bronchoscopy in the Diagnosis and Management of Patients with SARS-Cov-2 Infection

Bronchoscopy has several major diagnostic and therapeutic indications in pulmonology. However, it is an aerosol-generating procedure that places healthcare providers at an increased risk of infection. Now more than ever, during the spread of the coronavirus disease 2019 (COVID-19) pandemic, the infectious risk during bronchoscopy is significantly raised, and for this reason its role in diagnostic management is debated. In this review, we summarized current evidence regarding the indications for bronchoscopy and the measures that should be applied to decrease risk exposure. Indeed, seeing the long-lasting period of the pandemic, resuming standard of care for all patients is required.

P057 Virus aerosol propagation by CPAP is proportional to mask leak and can be prevented by use of a hood and air filtration system

Introduction Nosocomial transmission of SARS-CoV-2 has caused significant morbidity/mortality in the COVID-19 pandemic. Because patients auto-emit aerosols containing viable virus, these aerosols can be further propagated when patients undergo certain treatments including continuous positive airway pressure (PAP) therapy. This study aimed to assess the degree of viable virus propagated from mask leak in a PAP circuit. Methods Bacteriophage PhiX174 (108copies/mL) was nebulised into a custom PAP circuit. Mask leak was systematically varied to 0, 7, 21, 28 and 42 L/min at the mask interface. Plates containing Escherichia coli assessed the degree of viable virus settling on surfaces around the room. In order to contain virus spread a ventilated headboard and high efficiency particulate air (HEPA) filter was tested. Results Increasing mask leak was associated with virus contamination in a dose response manner (χ2= 58.24, df=4, p<0.001). Clinically relevant levels of leak (≥21 L/min) were associated with virus counts equivalent to using PAP with a standard vented mask. Viable viruses were recorded on all plates (up to 3.86m from source). A plastic hood with HEPA filtration significantly reduced viable viruses on all plates. HEPA exchange rates of 170 and 470m3/hr eradicated all evidence of virus contamination. Discussion Mask leak from PAP circuits may be a major source of environmental contamination and nosocomial spread of infectious respiratory diseases. Subclinical levels of leak should be treated as an infectious risk. Cheap and low-cost patient hoods with HEPA filtration are an effective countermeasure.

Inflammatory bowel disease and COVID-19: A review

The World Health Organization officially declared infection with severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), leading to coronavirus disease 2019 (COVID-19) as a Public Health Emergency of International Concern (PHEIC) on 30 January 2020 and then as a pandemic on March 11, 2020 with reports of infection from most of the countries of the world [1]. COVID-19 has severely disrupted prevention and treatment for noncommunicable diseases. Severe illness can occur in otherwise healthy individuals of any age, but it predominantly occurs in adults with advanced age or certain underlying medical comorbidities [2]. Since the beginning of the health emergency, particular attention has been paid to the management of patients with chronic Inflammatory Bowel Diseases (IBDs) because they frequently are treated with immunosuppressive drugs and therefore potentially are exposed to a greater infectious risk than the general population [3].