Myocarditis in anti-synthetase syndrome: clinical features and diagnostic modalities.

OBJECTIVES: Myocarditis is an overlooked manifestation of anti-synthetase syndrome (ASS). Our study describes the clinical and instrumental features of ASS-myocarditis and evaluates the diagnostic performance of cardiac magnetic resonance (CMR) with mapping techniques. METHODS: Data from ASS-patients were retrospectively analyzed. CMR data of patients diagnosed with myocarditis, including late gadolinium enhancement (LGE), T2-ratio, T1-mapping, extra-cellular volume (ECV) and T2-mapping, were reviewed. Myocarditis was defined by the presence of symptoms of heart involvement with increased high-sensitive troponin T (hs-TnT) and/or NT-proBNP and at least an instrumental abnormality. Clinical features of ASS patients with and without myocarditis were compared. A p value<0.05 was considered. RESULTS: Among a cohort of 43 ASS-patients (median age 58[48.0-66.0] years; females 74.4%; anti-Jo1 53.5%), 13(30%) were diagnosed with myocarditis. In 54% of patients, myocarditis was diagnosed at clinical onset. All ASS-myocarditis patients had at least one CMR abnormality: increased ECV in all cases, presence of LGE, increased T1 and T2-mapping in 91%. The 2009-Lake Louis criteria (LLC) were satisfied by 6 patients, the 2018-LLC by 10. With the updated LLC, the sensitivity for myocarditis improved from 54.6% to 91.0%. ASS-patients with myocarditis were more frequently males(53% vs 13%;p=0.009) with fever(69% vs 17%;p=0.001), and had higher hs-TnT (88.0[23.55-311.5] vs 9.80[5.0-23.0]ng/L; p < 0.001), NT-proBNP(525.5[243.5-1575.25] vs 59.0[32.0-165.5;p=0.013]pg/ml;p=0.013) and C-reactive protein(CRP)(7.0[1.7-15.75] vs 1.85[0.5-2.86]mg/L;p=0.011) compared to those without myocarditis. CONCLUSION: In ASS, myocarditis is frequent, even at clinical onset. ASS-patients with myocarditis frequently presented with fever and increased CRP, suggesting the existence of an inflammatory phenotype. The use of novel CMR mapping techniques may increase the diagnostic sensitivity for myocarditis in ASS.

Transoral incisionless fundoplication with Medigus ultrasonic surgical endostapler (MUSE) for the treatment of gastro-esophageal reflux disease: outcomes up to 3 years.

BACKGROUND: Transoral incisionless fundoplication (TIF) with Medigus Ultrasonic Surgical Endostapler (MUSE) is a new intervention for treatment of gastro-esophageal reflux disease (GERD). We aimed at assessing the clinical, functional, and endoscopic effects of TIF by MUSE. METHODS: Forty-six patients underwent TIF. Proton pump inhibitor (PPI) consumption, GERD-health-related quality of life (HRQL) and reflux symptom index (RSI) questionnaires, upper gastrointestinal (GI) endoscopy, esophageal 24-h pH-impedance recording, and high-resolution manometry (HRM) were done before TIF and scheduled 6 and 12 months later (HRM only at 6-month). PPI consumption and symptoms were then assessed yearly. Data up to 3 years are reported in this study (PP- and ITT-analysis). RESULTS: TIF was successfully performed in 45/46 patients; in one patient esophageal intubation was impossible. Perforation occurred in two cases. One patient required surgery within 6 months. Clinical follow-up was available for 42 patients at 6 months and 1 year, 35 patients at 2 years, and 31 patients at 3 years. At 1, 2, and 3 years, PPI consumption was stopped, respectively, in 64.3%, 62.9%, and 74.2% of cases (ITT-analysis: 58.7%, 56.4%, and 65.7%). GERD-HRQL and RSI scores decreased at least 50%, respectively, in 71.5% and 76.2%, 71.4% and 68.6%, and 67.7% of cases (ITT-analysis: 65.2% and 69.6%, 64.1% and 61.5%, and 60%). A significant improvement of both scores was observed up to 3 years. 6-month and 1-year functional follow-up were possible in 31 and 20 patients. HRM showed significant increase of the median lower esophageal sphincter length and rate of peristaltic waves. Esophageal pH-impedance recording found significantly fewer acid, proximal and total refluxes, and percentage of esophageal pH < 4 total time at 6 months, but not at 1 year. CONCLUSION: TIF by MUSE significantly improved symptoms and PPIs consumption up to 3 years. However, esophagitis still persisted in one-third of cases at 1 year and functional improvement at 6 months was not confirmed at 1 year. Severe complications requiring surgery occurred in two cases. CLINICALTRIALS: GOV: ID: NCT03669874.

The prognostic role of IL-10 in non-severe COVID-19 with chemosensory dysfunction.

OBJECTIVES: Olfactory and gustatory dysfunction (OD/GD) are now recognized as typical symptoms of COVID-19 infection. However, their pathogenesis remains unclear and no clear prognostic factors have been identified. We have analyzed a cohort of mild/moderate hospitalized patients to identify possible clinical or immunological predictors of recovery from OD/GD. METHODS: Clinical and biological parameters were reviewed along with associated comorbidities. Chemosensory Complaint Score was administered on admission and 30 days after the first negative swab. Unpaired Wilcoxon and chi-squared tests were used to compare the variables in the patients who recovered versus those who did not. RESULTS: From a cohort of 119 hospitalized patients, 43 (36%) reported OD/GD on admission. 60.6% had a full recovery from OD and 69.2% from GD. Only the concentration of IL-10 on admission emerged as significantly associated with recovery of taste (p = 0.041) while allergic respiratory disease was more prevalent in the group who did not recover from OD (p = 0.049) and GD (p = 0.007). CONCLUSION: These findings suggest that COVID-19 associated OD/GD is an inflammatory-mediated condition and that clinical and immunological parameters could predict the evolution of these symptoms.

Epidemiological analysis of a COVID-19 outbreak associated with an infected surgeon.

Control of the novel COronaVIrus Disease-2019 (COVID-19) in a hospital setting is a priority. A COVID-19-infected surgeon performed surgical activities before being tested. An exposure risk classification was applied to the identified exposed subjects and high- and medium-risk contacts underwent active symptom monitoring for 14 days at home. All healthcare professionals (HCPs) were tested for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) at the end of the quarantine and serological tests were performed. Three household contacts and 20 HCPs were identified as high- or medium-risk contacts and underwent a 14-day quarantine. Fourteen HCPs and 19 patients were instead classified as low risk. All the contacts remained asymptomatic and all HCPs tested negative for SARS-CoV-2. About 25-28 days after their last exposure, HCPs underwent serological testing and two of them had positive IgM but negative confirmatory swabs. In a low COVID-19 burden area, the in-hospital transmission of SARS-CoV-2 from an infectious doctor did not occur and, despite multiple and frequent contacts, a hospital outbreak was avoided. This may be linked to the adoption of specific recommendations and to the use of standard personal protective equipment by HCPs.

The impact of the COVID-19 pandemic on the quality of life of head and neck cancer survivors.

BACKGROUND: Head and neck cancer (HNC) survivors are particularly vulnerable to the deleterious consequences of lockdown and social distancing. The psychosocial effects of the COVID-19 pandemic on this group are still unknown, and we want to explore how their quality of life (QoL) has changed in this unique situation. MATERIALS AND METHODS: An online survey, composed of pandemic-specific items, plus the EORTC QLQ-C30, was administered to a cohort of HNC survivors. Using previously published reference values as a control group, we have evaluated the impact of the pandemic on their QoL. We have also explored the differences between those who had received a total laryngectomy (LP, laryngectomized population) vs other HNC patients, in order to assess the role of tracheostomy in this regard. RESULTS: One hundred and twenty-one HNC patients completed the survey. The scores of the physical (80.5 vs 85, p = 0.028), role (78 vs 84, p = 0.030), and emotional functioning (76 vs 81, p = 0.041) were significantly different in the two groups, with worse functioning in our patients. Comparing LP with the other HNC patients, social (76.6 vs 88.9, p = 0.008) and physical functioning (75.5 vs 86.1, p = 0.006) were significantly worse in the former group. LP also reported a greater perception that others are afraid to be close to them (1.67 vs 1.32, p = 0.020). No differences were found between LP with and without voice prosthesis. CONCLUSIONS: Our results show how HNC patients are at high risk for a worsening in QoL because of the ongoing COVID-19 global pandemic.

Transoral incisionless fundoplication with an ultrasonic surgical endostapler for the treatment of gastroesophageal reflux disease: 12-month outcomes.

BACKGROUND: Transoral incisionless fundoplication (TIF) with the Medigus ultrasonic surgical endostapler (MUSE) is a new intervention for the treatment of the gastroesophageal reflux disease (GERD). The aim of this study was to assess the 12-month clinical, functional, and endoscopic effects of TIF by MUSE. METHODS: Patients undergoing MUSE completed the GERD-Health Related Quality of Life (GERD-HRQL) and Reflux Symptom Index (RSI) questionnaires, and underwent endoscopy, esophageal 24-hour pH-impedance recording, and high resolution manometry (HRM) before the TIF procedure and 12 months later, or after 6 months for HRM. RESULTS: Among the 37 patients treated, esophageal intubation was not possible in one and esophageal perforation occurred in another. Clinical and endoscopic follow-up at 12 months was completed in 20 patients, with significant improvements in GERD-HRQL, RSI, heartburn, regurgitation scores, and proton pump inhibitor (PPI) consumption observed. One patient required surgery for persisting symptoms. Functional follow-up was possible in 13 patients and showed no significant improvements in the analyzed parameters. CONCLUSIONS: TIF with MUSE significantly improved symptoms at 1-year follow-up, allowing the consumption of PPIs to be stopped or halved in 90 % of patients.

Efficacy of Cetylpyridinium Chloride mouthwash against SARS-CoV-2: A systematic review of randomized controlled trials.

INTRODUCTION: COVID-19 is a transmissible respiratory and multisystem disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Viral transmission occurs mainly through the spread of salivary droplets or aerosol from an infected subject. Studies suggest that salivary viral load is correlated with disease severity and probability of transmission. Cetylpyridinium chloride mouthwash has been found to be effective in reducing salivary viral load. The aim of this systematic review of randomized controlled trials is to evaluate the efficacy of the mouthwash ingredient cetylpyridinium chloride on salivary viral load in SARS-CoV-2 infection. METHODS: Randomized controlled trials comparing cetylpyridinium chloride mouthwash with placebo and other mouthwash ingredients in SARS-CoV-2 positive individuals were identified and evaluated. RESULTS: Six studies with a total of 301 patients that met the inclusion criteria were included. The studies reported the efficacy of cetylpyridinium chloride mouthwashes in reduction on SARS-CoV-2 salivary viral load compared to placebo and other mouthwash ingredients. CONCLUSION: Mouthwashes containing cetylpyridinium chloride are effective against salivary viral load of SARS-CoV-2 in vivo. There is also the possibility that the use of mouthwash containing cetylpyridinium chloride in SARS-CoV-2 positive subjects could reduce transmissibility and severity of COVID-19.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): Focus on the Pathophysiological and Diagnostic Role of Viruses.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a heterogeneous, multiorgan and potentially life-threatening drug-hypersensitivity reaction (DHR) that occurs several days or weeks after drug initiation or discontinuation. DHRs constitute an emerging issue for public health, due to population aging, growing multi-organ morbidity, and subsequent enhanced drug prescriptions. DRESS has more consistently been associated with anticonvulsants, allopurinol and antibiotics, such as sulphonamides and vancomycin, although new drugs are increasingly reported as culprit agents. Reactivation of latent infectious agents such as viruses (especially Herpesviridae) plays a key role in prompting and sustaining aberrant T-cell and eosinophil responses to drugs and pathogens, ultimately causing organ damage. However, the boundaries of the impact of viral agents in the pathophysiology of DRESS are still ill-defined. Along with growing awareness of the multifaceted aspects of immune perturbation caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the ongoing SARS-CoV-2-related disease (COVID-19) pandemic, novel interest has been sparked towards DRESS and the potential interactions among antiviral and anti-drug inflammatory responses. In this review, we summarised the most recent evidence on pathophysiological mechanisms, diagnostic approaches, and clinical management of DRESS with the aim of increasing awareness on this syndrome and possibly suggesting clues for future research in this field.

Heart Rate Variability in Subjects with Severe Allergic Background Undergoing COVID-19 Vaccination.

Anti-Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccination is the world's most important strategy for stopping the pandemic. Vaccination challenges the body's immune response and can be complicated by hypersensitivity reactions. The autonomic nervous system can modulate the inflammatory immune response, therefore constituting a potential marker to characterize individuals at high risk of hypersensitivity reactions. Autonomic nervous system functionality was assessed through measurement of the heart rate variability (HRV) in subjects with a history of severe allergic reactions and 12 control subjects. HRV parameters included the mean electrocardiograph RR interval and the standard deviation of all normal R-R intervals (SDNN). All measurements were performed immediately before the anti-SARS-CoV-2 vaccination. The median RR variability was lower in the study than in the control group: 687 ms (645-759) vs. 821 ms (759-902); p = 0.02. The SDNN was lower in the study group than in the control group: 32 ms (23-36) vs. 50 ms (43-55); p < 0.01. No correlation was found between age and the SDNN. Autonomic nervous system activity is unbalanced in people with a severe allergy background.

Hypersensitivity reactions to anti-SARS-CoV-2 vaccines: Basophil reactivity to excipients.

Basophil activation test (BAT) can tackle multiple mechanisms underlying acute and delayed hypersensitivity to drugs and vaccines and might complement conventional allergy diagnostics but its role in anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine-related hypersensitivity is ill-defined. Therefore, 89 patients with possible hypersensitivity (56 % with delayed mucocutaneous manifestations) to anti-SARS-CoV-2 vaccines were tested with BAT for Macrogol 3350, DMG-PEG 2000, PEG 20000, polysorbate-80 and trometamol and compared to 156 subjects undergoing pre-vaccine BAT. A positive BAT was associated with delayed reaction onset (p = 0.010) and resolution (p = 0.011). BAT was more frequently positive to DMG-PEG 2000 than to other excipients in both groups (p < 0.001). DMG-PEG 2000 reactivity was less frequent in vaccine-naïve (6 %) than vaccinated subjects (35 %, p < 0.001) and associated with mRNA-1273 vaccination. DMG-PEG 2000 BAT might therefore have a diagnostic role in subjects with delayed hypersensitivity reactions. Natural immunity might be a key player in basophil activation.

Prevalence of Long COVID-19 Symptoms After Hospital Discharge in Frail and Robust Patients.

Background: A motley postacute symptomatology may develop after COVID-19, irrespective of the acute disease severity, age, and comorbidities. Frail individuals have reduced physiological reserves and manifested a worse COVID-19 course, during the acute setting. However, it is still unknown, whether frailty may subtend some long COVID-19 manifestations. We explored the prevalence of long COVID-19 disturbs in COVID-19 survivals. Methods: This was an observational study. Patients aged 65 years or older were followed-up 1, 3, and 6 months after hospitalization for COVID-19 pneumonia. Results: A total of 382 patients were enrolled. Frail patients were more malnourished (median Mini Nutritional Assessment Short Form score 8 vs. 9, p = 0.001), at higher risk of sarcopenia [median Strength, Assistance with walking, Rising from a chair, Climbing stairs, and Falls (SARC-F) score 3 vs. 1.5, p = 0.003], and manifested a worse physical performance [median Short Physical Performance Battery (SPPB) score 10 vs. 11, p = 0.0007] than robust individuals, after hospital discharge following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. Frailty was significantly associated with: (i) confusion, as a presenting symptom of COVID-19 [odds ratio (OR) 77.84, 95% CI 4.23-1432.49, p = 0.003]; (ii) malnutrition (MNA-SF: adjusted B -5.63, 95% CI -8.39 to -2.87, p < 0.001), risk of sarcopenia (SARC-F: adjusted B 9.11, 95% CI 3.10-15.13, p = 0.003), impaired muscle performance (SPPB: B -3.47, 95% CI -6.33 to -0.61, p = 0.02), complaints in mobility (adjusted OR 1674200.27, 95% CI 4.52-619924741831.25, p = 0.03), in self-care (adjusted OR 553305.56, 95% CI 376.37-813413358.35, p < 0.001), and in performing usual activities of daily living (OR 71.57, 95% CI 2.87-1782.53, p = 0.009) at 1-month follow-up; (iii) dyspnea [modified Medical Research Council (mMRC): B 4.83, 95% CI 1.32-8.33, p = 0.007] and risk of sarcopenia (SARC-F: B 7.12, 95% CI 2.17-12.07, p = 0.005) at 3-month follow-up; and (iv) difficulties in self-care (OR 2746.89, 95% CI 6.44-1172310.83, p = 0.01) at the 6-month follow-up. In a subgroup of patients (78 individuals), the prevalence of frailty increased at the 1-month follow-up compared to baseline (p = 0.009). Conclusion: The precocious identification of frail COVID-19 survivors, who manifest more motor and respiratory complaints during the follow-up, could improve the long-term management of these COVID-19 sequelae.

Interactions between Severe Allergy and Anxiety in Anti-SARS-CoV-2 Vaccinees.

Severe drug allergy affects patient hesitancy to new treatments, posing unprecedented challenges to anti-SARS-CoV-2 vaccination campaigns. We aimed to analyze the psychological profile of vaccinees with a history of severe allergy in comparison to subjects with a milder allergy history. Patients attending a dedicated vaccination setting were administered an anonymized questionnaire including clinical data and the State-Trait Anxiety Inventory (STAI) scale (score range 20−80). Patients were also asked whether being in a protected setting affected their attitude toward vaccination. Data are expressed as median (interquartile range). We enrolled 116 patients (78% women), of whom 79% had a history of drug anaphylaxis. The median state anxiety score was 36.5 (30−47.2), while the trait anxiety score was 37 (32−48). State anxiety was higher in those with severe than mild allergy [39 (32−50) vs. 30 (25−37); p < 0.001], with the highest score found in a patient with previous drug anaphylaxis (42.5 [32−51.7]). More than 50% of patients reported that being in a protected setting had lowered their anxiety. Severe allergy is associated with a higher burden of situational anxiety in the setting of vaccination without affecting patient constitutional (trait) levels of anxiety. Vaccination in dedicated facilities might overcome issues related to hesitancy and improve patients' quality of life.

The Mismatch Repair System (MMR) in Head and Neck Carcinogenesis and Its Role in Modulating the Response to Immunotherapy: A Critical Review.

The mismatch repair (MMR) system has a major role in the detection and correction of DNA replication errors, resulting from DNA polymerase slippage or nucleotides misincorporation. Specific inherited/acquired alterations or epigenetic inactivation of MMR genes are associated with microsatellite instability (MSI): the loss of crucial function in repairing DNA alterations can promote carcinogenesis by favoring the accumulation of thousands of mutations in a broad spectrum of different anatomic sites such as colon, stomach, prostate, esophagus, endometrium, lung and head and neck. Recent extensive data suggest that tumor mutational burden strongly correlates with a clinical response to immunotherapy using checkpoint inhibitors and this response is influenced by MMR deficiency in a wide range of human solid cancers. In this context, few data about this crucial point are available for head and neck cancer (HNC). In this review, we discuss the role of MMR alterations and the resulting MSI in HNC pathogenesis. Furthermore, by summarizing the clinical available data on how they influence the progression of precancerous lesions and the risk of recurrence or second primary tumors, we want to define the current role of MSI in the management of HNC. Finally, we analyze the complex interaction between cancer cells and the immune system addressing the data now available about a potential correlation between microsatellite instability and immunotherapy response in HNC.

The clinical consequences of the COVID-19 lockdown: A report from an Italian referral ENT department.

Objectives: To evaluate the clinical effects of health care reorganization because of COVID-19, in a non-red zone Italian referral department of Otorhinolaryngology. Materials and Methods: We retrospectively reviewed the statistics of admissions to the Emergency Department (ED) of the Careggi University Hospital, Florence, from January 1, 2020, to May 17, 2020. Data regarding elective and urgent head and neck disorders were reviewed and the most challenging cases were discussed. Results: During the lockdown period, outpatient otolaryngological consultations and elective procedures decreased by 78% and 75% respectively, while emergency/urgency surgery increased by 128%. The five most emblematic clinical cases were thoroughly analyzed. Conclusion: Our analysis shows how the profound rearrangement of clinical and surgical activities, along with the citizens' fear to seek medical care has probably exacerbated the management of many routine head and neck conditions. Level of Evidence: 4.