Descending necrotizing mediastinitis caused by retro-pharyngeal Eggerthia catenaformis infection.

Introduction: Eggerthia catenaformis, a non-spore-forming anaerobic Gram-positive bacillus component of the human fecal microbiota has rarely been reported in human diseases. In almost every case described in current literature to date, dental diseases (abscesses, periodontitis, or caries), are the most common source of the infection which extends to the brain, cervical spaces, pulmonary parenchyma, the pleural cavity, the abdominal wall, and the abdominal cavity. Case report: An 82-year-old male Caucasian patient was admitted to our Emergency Department (ED) with a painless, right submandibular mass, dyspnea, and inspiratory stridor. A CT scan of the head, neck, and chest with intravenous contrast material revealed a retrotonsillar fluid collection. Air bubbles and minimal fluid were present from the right sub-mandibular area to the lower mediastinum between the spine, the descending thoracic aorta, and the trachea. The patient underwent surgical treatment and a broad-spectrum antibiotic. The retropharyngeal fluid collection culture showed the presence of Eggerthia catenaformis. After a first period in the Intensive Care Unit, he was admitted to a Step-Down Unit (SDU) where he underwent respiratory weaning, motor rehabilitation, and gradual oral feeding resumption. At discharge, the patient maintained the tracheal cannula as he still had impaired swallowing of solid foods. Conclusions: Here we report the first case of descending necrotizing mediastinitis in a patient with a retropharyngeal abscess, in the absence of dental diseases.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike Protein S1 Induces Methylglyoxal-Derived Hydroimidazolone/Receptor for Advanced Glycation End Products (MG-H1/RAGE) Activation to Promote Inflammation in Human Bronchial BEAS-2B Cells.

The pathogenesis of coronavirus disease 2019 (COVID-19) is associated with a hyperinflammatory response. The mechanisms of SARS-CoV-2-induced inflammation are scantly known. Methylglyoxal (MG) is a glycolysis-derived byproduct endowed with a potent glycating action, leading to the formation of advanced glycation end products (AGEs), the main one being MG-H1. MG-H1 exerts strong pro-inflammatory effects, frequently mediated by the receptor for AGEs (RAGE). Here, we investigated the involvement of the MG-H1/RAGE axis as a potential novel mechanism in SARS-CoV-2-induced inflammation by resorting to human bronchial BEAS-2B and alveolar A549 epithelial cells, expressing different levels of the ACE2 receptor (R), exposed to SARS-CoV-2 spike protein 1 (S1). Interestingly, we found in BEAS-2B cells that do not express ACE2-R that S1 exerted a pro-inflammatory action through a novel MG-H1/RAGE-based pathway. MG-H1 levels, RAGE and IL-1ß expression levels in nasopharyngeal swabs from SARS-CoV-2-positive and -negative individuals, as well as glyoxalase 1 expression, the major scavenging enzyme of MG, seem to support the results obtained in vitro. Altogether, our findings reveal a novel mechanism involved in the inflammation triggered by S1, paving the way for the study of the MG-H1/RAGE inflammatory axis in SARS-CoV-2 infection as a potential therapeutic target to mitigate COVID-19-associated pathogenic inflammation.

Case report: Coxiella burnetii endocarditis in the absence of evident exposure.

Q fever is a worldwide zoonotic disease caused by Coxiella burnetii. In humans, it can manifest clinically as an acute or chronic disease and endocarditis, the most frequent complication of chronic Q fever is associated with the greatest morbidity and mortality. We report a severe case of endocarditis in a 55-year-old man with a history of aortic valve replacement affected by monoclonal gammopathy of undetermined significance (MGUS), and living in a non-endemic area for C. burnetii. After two episodes of fever of unknown origin (FUO), occurring 2 years apart and characterized by negative blood cultures, a serological diagnosis of Q fever endocarditis was performed even though the patient did not refer to possible past exposure to C. burnetii. Since people with preexisting valvular heart disease, when infected with C. burnetii, have reported a 40% risk of Q fever endocarditis, clinicians should maintain a high index of suspicion for infective endocarditis in all patients with FUO even when the exposure to C. burnetii appears to be unlikely.

Immune correlates of protection by vaccine against SARS-CoV-2 in patients with chronic lymphocytic leukaemia.

In chronic lymphocytic leukaemia (CLL) the efficacy of SARS-CoV-2 vaccination remains unclear as most studies have focused on humoral responses. Here we comprehensively examined humoral and cellular responses to vaccine in CLL patients. Seroconversion was observed in 55.2% of CLL with lower rate and antibody titres in treated patients. T-cell responses were detected in a significant fraction of patients. CD4+ and CD8+ frequencies were significantly increased independent of serology with higher levels of CD4+ cells in patients under a Bruton tyrosine kinase (BTK) or a B-cell lymphoma 2 (BCL-2) inhibitor. Vaccination skewed CD8+ cells towards a highly cytotoxic phenotype, more pronounced in seroconverted patients. A high proportion of patients showed spike-specific CD4+ and CD8+ cells producing interferon gamma (IFNγ) and tumour necrosis factor alpha (TNFα). Patients under a BTK inhibitor showed increased production of IFNγ and TNFα by CD4+ cells. Vaccination induced a Th1 polarization reverting the Th2 CLL T-cell profile in the majority of patients with lower IL-4 production in untreated and BTK-inhibitor-treated patients. Such robust T-cell responses may have contributed to remarkable protection against hospitalization and death in a cohort of 540 patients. Combining T-cell metrics with seroprevalence may yield a more accurate measure of population immunity in CLL, providing consequential insights for public health.

Multimodal assessment in polymicrobial infective endocarditis with silent spondylodiscitis and cerebral embolism / Evaluación multimodal en endocarditis infecciosa polimicrobiana con espondilodiscitis silenciosa y embolia cerebral

Abstract Infective endocarditis (IE) is a rare but severe disease, due to an infection of the endocardial surface of the heart. The annual incidence ranging from 3 to 7 per 100 000 person-years, with an overall mortality rates of 25%. Staphylococci and Streptococci accounted for approximately 80% of IE cases. Enterococci are the third leading cause accounted for approximately 5-18% of all cases and are increasingly linked to health-care contact. The increasing number of cardiovascular electronic devices, prosthetic valves implants along with frequent invasive diagnostic or therapeutic procedures performed in elderly, may also contribute to the rise of IE in this population. Blood cultures and echocardiographic findings are the cornerstone of the IE diagnosis, confirmed or rejected according to modified Duke criteria. Other imaging modalities as Cardiac Computed Tomography, Cardiac Magnetic Resonance Imaging and 18Ffluorodeoxyglucose Positron Emission Tomography - Computed Tomography (18FDG-PET/CT) can determine a more correct diagnosis and identify many of the endocarditis-related complications. Here, we describe a patient with aortic prosthetic valve and Enterococcus faecalis (EF) IE. Cerebral and spinal MRI and 18FDG-PET/CT, performed during the hospitalization, showed multi-organ silent periferic embolization. Furthermore, the cultural examination of the valvular surgical specimen revealed a methicillin-sensitive Staphylococcus aureus suggestive for polymicrobial endocarditis. Some Authors demonstrated a possible false-positive valve culture due to a postoperative contamination. Since contaminated cultures usually yield microorganisms compatible with endocarditis, such as coagulase-negative Staphylococci, viridans group Streptococcus species, may be difficult for the physician not to treat the patient. This case represents need for high level of suspicion to diagnose IE. Multimodality assessment improves the diagnosis and allows the detection of the complications. Moreover, a multidisciplinary team and specialized centers determine a better patient’s outcome.

Resumen La endocarditis infecciosa (EI) es una enfermedad poco frecuente pero severa, dada por una infección del endocardio. La incidencia anual oscila entre 3 y 7 por cada 100 000 personas-año, con una tasa de mortalidad general del 25%. Los estafilococos y los estreptococos representaron aproximadamente un 80% de los casos de EI. Los enterococos son la tercera causa, aportando aproximadamente 5% a 18% de todos los casos, y se vinculan cada vez más al contacto con la atención médica. El número creciente de dispositivos electrónicos cardiovasculares e implantes de válvulas protésicas, junto con los frecuentes procedimientos invasivos diagnósticos o terapéuticos en las personas ancianas, también podrían contribuir al incremento de EI en esta población. Los hemocultivos y los hallazgos ecocardiográficos son la piedra angular del diagnóstico de EI, confirmado o rechazado de acuerdo con los criterios modificados de Duke. Otras modalidades de imagenología tales como la Tomografía Computarizada Cardíaca (TCC), la Resonancia Magnética Cardíaca (RMC) y la Tomografía por Emisión de Positrones - Tomografía Computarizada con 18F-fluorodeoxiglucosa (18F-FDG PET/TC) pueden determinar un diagnóstico más preciso e identificar muchas de las complicaciones asociadas a la endocarditis. Aquí describimos un paciente con una válvula aórtica protésica y EI por EF. Una RM del cerebro y la columna vertebral y una 18F-FDG PET/TC practicadas durante la hospitalización evidenciaron embolia periférica multiorgánica silenciosa. Además, el examen por cultivo de la muestra quirúrgica valvular reveló Staphylococcus aureus sensible a la meticilina (SASM), sugestivo de endocarditis polimicrobiana. Algunos autores demostraron un posible falso positivo del cultivo valvular dado por contaminación postoperatoria. Ya que los cultivos contaminados generalmente producen microorganismos compatibles con la endocarditis, tales como estafilococos coagulasa negativos y estreptococos del grupo viridans, le puede resultar difícil al médico no tratar al paciente. Este caso representa la necesidad de tener un alto nivel de sospecha para diagnosticar la EI. La valoración multimodal mejora el diagnóstico y permite detectar complicaciones. Además, un equipo multidisciplinario y los centros especializados determinan un mejor desenlace para el paciente.

Role of Nucleocapsid Protein Antigen Detection for Safe End of Isolation of SARS-CoV-2 Infected Patients with Long Persistence of Viral RNA in Respiratory Samples.

BACKGROUND: In SARS-CoV-2 infection, viral RNA may persist in respiratory samples for several weeks after the resolution of symptoms. Criteria to assess the end of infectivity are not unequivocally defined. In some countries, time from diagnosis is the unique criterion used, in addition to symptom cessation. This study evaluates the role of the Lumipulse® Antigen Assay (LAA) for the safe end of isolation of patients ≥21 days after the diagnosis of infection. METHODS: A total of 671 nasopharyngeal swabs from patients diagnosed with infection at least 21 days before were assessed by RT-PCR and LAA, and the role of LAA in predicting the absence of infectivity was evaluated by virus cell culture. RESULTS: Viable virus was present in 10/138 cultured samples. Eight out of ten infective patients suffered from a concomitant disease, predisposing them to long-term shedding of infective virus. In particular, infectious virus was isolated from 10/20 RT-PCR+/LAA+ cultured samples, whereas no viable virus was found in all 118 RT-PCR+/LAA- cultured swabs. LLA and RT-PCR agreed in 484/671 (72.1%) samples, with 100% and 26.7% concordance in RT-PCR negative and positive samples, respectively. CONCLUSIONS: Viable virus can be found ≥21 days after diagnosis in immunocompromised or severely ill patients. LAA better than RT-PCR predicts non-infectivity of patients and can be safely used to end isolation in cases with long persistence of viral RNA in the respiratory tract.

Resolution of pulmonary artery thrombosis in patients with moderate COVID-19 disease.

Novel Coronavirus disease (COVID-19) has been widely described as the cause for a proinflammatory and hypercoagulable state. The inflammatory process involving the alveolar vascular endothelium in the respiratory system, is a determining factor for the onset of primary Pulmonary Artery Thrombosis (PAT) even in patients with heparin prophylactic treatment. Little is known about the efficacy of the anticoagulant therapy during the course of PAT caused by COVID-19. In this paper we describe the results obtained in patients with moderate COVID-19 disease, previously threated with prophylactic enoxaparin, who then received full Anticoagulant treatment after diagnosis of PAT. After three months Computed Tomography Pulmonary Angiography demonstrated a complete resolution of the vascular obstructive lesions in all patients, while all the coagulation tests were normal.

Evaluation of Lumipulse® G SARS-CoV-2 antigen assay automated test for detecting SARS-CoV-2 nucleocapsid protein (NP) in nasopharyngeal swabs for community and population screening.

OBJECTIVES: To compare the Lumipulse® SARS-CoV-2 antigen test with the gold standard real-time reverse transcription-polymerase chain reaction (RT-PCR) for diagnosis of SARS-CoV-2 infection and to evaluate its role in screening programs. METHODS: Lumipulse® SARS-CoV-2 antigen assay was compared with the gold standard RT-PCR test in a selected cohort of 226 subjects with suspected SARS-CoV-2 infection, and its accuracy was evaluated. Subsequently, the test was administered to a real-life screening cohort of 1738 cases. ROC analysis was performed to explore test features and cutoffs. All tests were performed in the regional reference laboratory in Umbria, Italy. RESULTS: A 42.0% positive result at RT-PCR was observed in the selected cohort. The Lumipulse® system showed 92.6% sensitivity (95% CI 85.4-97.0%) and 90.8% specificity (95% CI 84.5-95.2%) at 1.24 pg/mL optimal cutoff. In the screening cohort, characterized by 5.2% prevalence of infection, Lumipulse® assay showed 100% sensitivity (95% CI 96.0-100.0%) and 94.8% specificity (95% CI 93.6-95.8%) at 1.645 pg/mL optimal cutoff; the AUC was 97.4%, NPV was 100% (95% CI 99.8-100.0%) and PPV was 51.1% (95% CI 43.5-58.7%). CONCLUSIONS: The Lumipulse® SARS-CoV-2 antigen assay can be safely employed in the screening strategies in small and large communities and in the general population.

Hypoventilation improvement in an adult non-invasively ventilated patient with Rapid-onset Obesity with Hypothalamic Dysfunction Hypoventilation and Autonomic Dysregulation (ROHHAD).

Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) is a rare disease of unknown etiology, characterized by rapid-onset obesity in young children, hypoventilation, hypothalamic and autonomic dysfunction. Patients between the ages of 2 and 4 present with hyperphagia and weight gain, followed by neuro-hormonal dysfunction and central hypoventilation months or years later. Cardiac arrest may represent the fatal complication of alveolar hypoventilation and early mechanical ventilation is essential for the patient's life. In this paper, we describe a 22-year-old patient with ROHHAD syndrome who had an acute respiratory failure during nocturnal non-invasive ventilation (NIV).

Pulmonary scintigraphy as a method to investigate gastrobronchial communication in tracheostomized patients.

Amyotrophic Lateral Sclerosis (ALS) is a degeneration of somatic motor neurons extending from upper motor cortical pyramidal neurons to lower motor neurons of the brainstem and cord. During the course of the disease patients require invasive procedures for nutrition and ventilation. Percutaneous Endoscopic Gastrostomy (PEG), performed in patients with impaired swallowing, is a safe procedure for the administration of Enteral Nutrition (EN). In the advanced stages of the disease patients develop a ventilatory failure due to muscolar weakness in these case they need a permanent tracheal tube with mechanical ventilation. Here we reported a case of a patient with Amyotrophic Lateral Sclerosis (ASL) who developed an increased gastric endocavitary pressure after a Percutaneous Endoscopic Gastrostomy (PEG).

The excitability of the trigeminal motor system in sleep bruxism: a transcranial magnetic stimulation and brainstem reflex study.

AIMS: Since sleep bruxism (SB) is characterized by grinding and clenching of the teeth during sleep and could be an exaggerated manifestation of normal spontaneous rhythmic masticatory muscle activity, the aim of this study was to obtain a neurophysiological assessment of the excitability of the central jaw motor pathways in patients with signs and symptoms suggestive of SB. METHODS: A total of 30 subjects diagnosed with SB on the basis of self-report of tooth grinding were studied using the "recovery cycle" of the masseter inhibitory reflex (MIR) elicited by electric and magnetic stimulation of the mental nerves and by recording the motor potentials evoked in masseter muscles by transcranial magnetic stimulation. Tests were done during daytime, when the subjects were awake. The data obtained were compared with data from a population of normal subjects. RESULTS: In the putative SB patients and in normal subjects, the MIRs evoked by single electric and magnetic stimuli were similar. With paired stimuli, the degree of suppression of the late silent period was significantly lower (P < .01) in the patients compared to normal subjects, particularly for magnetic stimuli, at various interstimulus intervals. No significant differences were found between the 2 groups of subjects in the masseter motor potentials evoked by transcranial magnetic stimulation. CONCLUSION: Although the data were only obtained during wakefulness in patients self-reporting signs and symptoms suggestive of SB, the findings suggest that an abnormal excitability of the central jaw motor pathways may be present in SB subjects. This increased excitability could derive from an impaired modulation of brainstem inhibitory circuits and not from altered cortical mechanisms. These results support the view that bruxism is mainly centrally mediated and that it involves subcortical structures. The study also indicates that use of the MIR elicited by the double-shock technique could be valuable in the evaluation of bruxism.