Sepsis Outcome after Major Abdominal Surgery Does Not Seem to Be Improved by the Use of Pentameric Immunoglobulin IgM: A Single-Center Retrospective Analysis.

BACKGROUND: Sepsis still represents a major public health issue worldwide, and the immune system plays a main role during infections; therefore, its activity is mandatory to resolve this clinical condition. In this report, we aimed to retrospectively verify in a real-life setting the possible usefulness of pentameric IgM plus antibiotics in recovering patients with sepsis after major abdominal surgery. MATERIALS/METHODS: We reviewed, from January 2013 until December 2019, all adult patients admitted to the ICU for sepsis or septic shock (2) after major abdominal surgery. Among these patients, were identified those that, according to legal indication and licenses in Italy, were treated with pentameric IgM plus antibiotics (Group A) or with antibiotics alone (Group B). The following parameters were evaluated: blood gas analysis, lactate, CRP, procalcitonin, endotoxin activity, liver and renal function, coagulation and blood cell count at different time points (every 48 h for at least 7 days). Differences between groups were analyzed using Fisher's exact test or a chi-square test for categorical variables. A Mann-Whitney U test or Kruskal-Wallis test were instead been performed to compare continuous variables. Univariate and multivariate analysis were also performed. RESULTS: Over a period of 30 months, 24 patients were enrolled in Group A and 20 patients in Group B. In those subjects, no statistical differences were found in terms of bacterial or fungal infection isolates, when detected in a blood culture test, or according to inflammatory index, a score, lactate levels and mortality rate. A 48 h response was statistically more frequent in Group B than in Group A, while no differences were found in other clinical and laboratory evaluations. CONCLUSIONS: Based on our results, the use of pentameric IgM does not seem to give any clinical advantages in preventing sepsis after major abdominal surgery.

Deep Neck Infections: Decisional Algorithm for Patients with Multiple Spaces Involvement.

BACKGROUND: Deep Neck Infections (DNIs) spread along fascial planes and involve neck spaces. Recently, their incidence has decreased due to the introduction of antibiotics; nevertheless, complications related to DNIs are often life-threatening. OBJECTIVE: The purpose of this article is focused on the identification of predisposing factors of these complications, as well as on the development of a reliable therapeutic algorithm. METHODS: Sixty patients with DNIs were enrolled from 2006 to 2019 for a retrospective study. The exclusion criteria for the present study were cellulitis, small abscesses responding to empiric or specific antibiotic therapy, or involvement of only one deep neck space. During the analysis, the following parameters of interest have been evaluated: gender, age, site of origin, pathways of spread, comorbidities, clinical features, bacteriology data, type of surgical approach required, complications, duration of hospitalization and mortality rate. On admission, microbial swab analysis was performed. RESULTS: Diabetes Mellitus (DM), Chronic Obstructive Pulmonary Disease (COPD), iron deficiency anemia and the involvement of multiple spaces have been associated with a significantly higher risk of developing complications. Most of our patients had polymicrobial infections. All patients underwent surgical drainage. The complication rate had occurred in 56.6% of patients, while death in 18.3%. CONCLUSION: DNIs represent a medical and surgical emergency with potentially serious complications; thus, avoidance of diagnostic delay is mandatory. Our preliminary data suggest the importance of evaluating the extent of infections because the involvement of multiple spaces requires timely surgery due to the higher risk of complications and mortality.

Tonic modulation of GABA release by nicotinic acetylcholine receptors in layer V of the murine prefrontal cortex.

By regulating the neocortical excitability, nicotinic acetylcholine receptors (nAChRs) control vigilance and cognition and are implicated in epileptogenesis. Modulation of gamma-aminobutyric acid (GABA) release often accompanies these processes. We studied how nAChRs regulate GABAergic transmission in the murine neocortex with immunocytochemical and patch-clamp methods. The cholinergic fibers densely innervated the somatosensory, visual, motor, and prefrontal cortices (PFC). Laminar distribution was broadly homogeneous, especially in the PFC. The cholinergic terminals were often adjacent to the soma and dendrites of GABAergic interneurons, but well-differentiated synapses were rare. Tonically applied nicotine (1-100 microM) increased the frequency of spontaneous GABAergic inhibitory postsynaptic currents (IPSCs) on pyramidal neurons in PFC layer V. The contribution of nAChR types was assessed by using 1 microM dihydro-beta-erythroidine (DHbetaE), to block heteromeric nAChRs, and 10 nM methyllycaconitine (MLA), to block homomeric nAChRs. Both inhibitors antagonized the effect of nicotine on IPSCs, suggesting that mixed nAChR types control pyramidal neuron inhibition in layer V. To determine whether nAChRs are expressed on basket cells' terminals, we studied miniature IPSCs (mIPSCs). These were revealed using 0.5 microM tetrodotoxin and 50 microM Cd(2+) to isolate the GABAergic terminals from the action potential drive. The nicotinic stimulation of mIPSCs was antagonized by DHbetaE, but not MLA, indicating that heteromeric nAChRs prevail in GABAergic terminals. Immunocytochemistry confirmed the expression of nAChRs on basket cells' somata and terminals. Finally, when the ionotropic glutamatergic transmission was blocked, nicotine partially inhibited the IPSCs, an effect counteracted by both DHbetaE and MLA. Therefore, a fraction of nAChRs are capable of activating GABAergic interneurons that in turn inhibit other GABAergic interneurons, thereby reducing the IPSCs. We conclude that heteromeric nAChRs control GABA release presynaptically, whereas mixed nAChRs regulate both excitation and inhibition of interneurons, the balance depending on the overall glutamatergic drive.

Sudden Sensorineural Hearing Loss in Mild COVID-19: Case Series and Analysis of the Literature.

BACKGROUND: There is growing evidence of otoneurological involvement of SARS-CoV-2, such as tinnitus and balance disorders and smell and taste disorders, but HL in COVID-19 patients has still been marginally studied. Investigating the role of SARS-CoV-2 as an aetiological factor of Sudden Sensorineural Hearing Loss (SSNHL) may offer the opportunity to address treatment strategies to maximize clinical recovery and avoid side effects. METHODS AND RESULTS: For this purpose, we will present case studies of five patients who experienced SSNHL during COVID-19. Patients were selected from COVID-19 positive adult subjects with mild clinical presentation, admitted to the outpatient Ear Nose and Throat Department of Cardarelli Hospital due to the onset of SSNHL during the infection. All underwent a complete audio-vestibular investigation before and after SSNHL treatment protocol. Each patient is described with a detailed analysis. CONCLUSIONS: SSNHL could be an occasional symptom of COVID-19, even in mild manifestations of the disease. Our experience leads us to underline the value of promptly recognizing and addressing this and other uncommon symptoms, giving patients the opportunity to receive early treatment.

SARS-CoV-2 in Urine May Predict a Severe Evolution of COVID-19.

We hypothesized that the spread of SARS-CoV-2 in urine during a severe COVID-19 infection may be the expression of the worsening disease evolution. Therefore, the aim of this study was to verify if the COVID-19 disease severity is related to the viral presence in urine samples. We evaluated the clinical evolution in acute COVID-19 patients admitted in the sub-intensive care and intensive care units between 28 of December 2020 and 15th of February 2021 and being positive for SARS-CoV-2 RNA in the respiratory tract, including repeated endotracheal aspirates (ETA), sputum, nasopharyngeal swabs (NPS) and urine. We found that those subjects with SARS-COV-2 in the urine at admittance (8 out of 60 eligible patients) had a more severe disease than those with negative SARS-CoV-2 in urine. Further, they showed an increase in fibrinogen and (C-reactive Protein) CRP serum levels, requiring mechanic ventilation. Of those with positive SARS-CoV-2 in the urine, 50% died. According to our preliminary results, it seems that the presence of SARS-CoV-2 in the urine characterizes patients with a more severe disease and is also related to a higher death rate.

Our Experience on Temporal Bone Fractures: Retrospective Analysis of 141 Cases.

Temporal bone fractures are a common lesion of the base of the skull. The diagnosis and management of temporal bone fractures require a multidisciplinary approach. Variable clinical presentations may arise from such fractures, ranging from an asymptomatic course to very serious consequences. The aim of this study was to report our experience with a series of patients with temporal bone fractures and to propose a diagnostic/therapeutic algorithm. This study enrolled 141 patients, 96 (68.1%) males and 45 (31.9%) females, ranging in age from 20 to 60 (average age: 39 ± 4.1 years), with temporal bone fractures who were referred to Cardarelli Hospital between 2006 and 2018. The present paper presents a classification of temporal bone fractures and typical clinical sequelae and provides an illustration of their prognosis and treatment.

Diagnosis of benign paroxysmal positional vertigo in Emergency Department: Our experience.

The Benign Paroxysmal Positional Vertigo (BPPV) represents the first cause of peripheral vertigo in populations and it is determined by a displacement of otoconial fragments within the semicircular canals. Following the patient's head movements, these fragments, moving by inertia, incorrectly stimulate the canals generating vertigo. The BPPV is diagnosable by observing the nystagmus that is generated in the patient following the Dix-Hallpike maneuver used for BPPV diagnosis of vertical semi-circular canal, and, following the supine head yaw test used for lateral semi-circular canal. Correctly identifying the origin of this specific peripheral vertigo, would mean to obtain a faster diagnosis and an immediate resolution of the problem for the patient. In this context, this study aims to identify precise training activities, aimed at the application of specific diagnostic maneuverers for algorithm decisions in support of medical personnel. The evaluations reported in this study refer to the data collected in the Emergency Department of the Cardarelli Hospital of Naples. The results obtained, over a six-month observation period, highlighted the advantages of the proposed procedures in terms of costs, time and number of BPPV diagnoses.

Pharmacological characterisation of CR6086, a potent prostaglandin E2 receptor 4 antagonist, as a new potential disease-modifying anti-rheumatic drug.

BACKGROUND: Prostaglandin E2 (PGE2) acts via its EP4 receptor as a cytokine amplifier (e.g., interleukin [IL]-6) and induces the differentiation and expansion of inflammatory T-helper (Th) lymphocytes. These mechanisms play a key role in the onset and progression of rheumatoid arthritis (RA). We present the pharmacological characterisation of CR6086, a novel EP4 receptor antagonist, and provide evidence for its potential as a disease-modifying anti-rheumatic drug (DMARD). METHODS: CR6086 affinity and pharmacodynamics were studied in EP4-expressing HEK293 cells by radioligand binding and cyclic adenosine monophosphate (cAMP) production, respectively. In immune cells, IL-6 and vascular endothelial growth factor (VEGF) expression were analysed by RT-PCR, and IL-23 and IL-17 release were measured by enzyme-linked immunosorbent assay (ELISA). In collagen-induced arthritis (CIA) models, rats or mice were immunised with bovine collagen type II. Drugs were administered orally (etanercept and methotrexate intraperitoneally) starting at disease onset. Arthritis progression was evaluated by oedema, clinical score and histopathology. Anti-collagen II immunoglobulin G antibodies were measured by ELISA. RESULTS: CR6086 showed selectivity and high affinity for the human EP4 receptor (Ki = 16.6 nM) and functioned as a pure antagonist (half-maximal inhibitory concentration, 22 nM) on PGE2-stimulated cAMP production. In models of human immune cells in culture, CR6086 reduced key cytokine players of RA (IL-6 and VEGF expression in macrophages, IL-23 release from dendritic cells, IL-17 release from Th17 cells). In the CIA model of RA in rats and mice, CR6086 significantly improved all features of arthritis: severity, histology, inflammation and pain. In rats, CR6086 was better than the selective cyclooxygenase-2 inhibitor rofecoxib and at least as effective as the Janus kinase inhibitor tofacitinib. In mice, CR6086 and the biologic DMARD etanercept were highly effective, whereas the non-steroidal anti-inflammatory drug naproxen was ineffective. Importantly, in a study of CR6086/methotrexate, combined treatment greatly improved the effect of a fully immunosuppressive dose of methotrexate. CONCLUSIONS: CR6086 is a novel, potent EP4 antagonist showing favourable immunomodulatory properties, striking DMARD effects in rodents, and anti-inflammatory activity targeted to immune-mediated inflammatory diseases and distinct from the general effects of cyclooxygenase inhibitors. These results support the clinical development of CR6086, both as a stand-alone DMARD and as a combination therapy with methotrexate. The proof-of-concept trial in patients with RA is ongoing.

Interleukin-10 and tumor necrosis factor-alpha: model of immunomodulation in multiple sclerosis.

OBJECTIVES: The mechanisms involved in the pathogenesis of relapsing-remitting multiple sclerosis are still unclear. The aim of the present study was to evaluate both cerebrospinal fluid (CSF) CD4+ CD7+ T cells and peripheral blood (PB) interleukin-10 (IL-10) as well as tumor necrosis-alpha (TNF-alpha) levels in patients with definite multiple sclerosis of the relapsing-remitting type. METHODS: To assess the above-mentioned cytokine levels we performed our test by the means of ELI-spot assay; the T-helper cell subset was assayed using flow cytometry. RESULTS: PB IL-10 levels of multiple sclerosis (MS) patients in remission were significantly (p<0.001) higher than in MS patients in the active phase. There was significant and increased evidence of TNF-alpha levels only in the MS patients in the active phase. CD4+ CD7+ T cells, characterized by a preferential Th1-like cytokine profile, were detectable only in seven patients in the active phase without evidence of a statistical significance with respect to cytokine levels. CONCLUSION: The data indicate that the production of different cytokines characterized the expression of relapsing-remitting MS. The data also suggest that is it possible to control MS using the regulatory cytokine balance.