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Background The role of neuromuscular blocking agents (NMBAs) in coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS) is not fully elucidated. Therefore, we aimed to investigate in COVID-19 patients with moderate-to-severe ARDS the impact of early use of NMBAs on 90-day mortality, through propensity score (PS) matching analysis. Methods We analyzed a convenience sample of patients with COVID-19 and moderate-to-severe ARDS, admitted to 244 intensive care units within the COVID-19 Critical Care Consortium, from February 1, 2020, through October 31, 2021. Patients undergoing at least 2 days and up to 3 consecutive days of NMBAs (NMBA treatment), within 48 h from commencement of IMV were compared with subjects who did not receive NMBAs or only upon commencement of IMV (control). The primary objective in the PS-matched cohort was comparison between groups in 90-day in-hospital mortality, assessed through Cox proportional hazard modeling. Secondary objectives were comparisons in the numbers of ventilator-free days (VFD) between day 1 and day 28 and between day 1 and 90 through competing risk regression. Results Data from 1953 patients were included. After propensity score matching, 210 cases from each group were well matched. In the PS-matched cohort, mean (± SD) age was 60.3 ± 13.2 years and 296 (70.5%) were male and the most common comorbidities were hypertension (56.9%), obesity (41.1%), and diabetes (30.0%). The unadjusted hazard ratio (HR) for death at 90 days in the NMBA treatment vs control group was 1.12 (95% CI 0.79, 1.59, p = 0.534). After adjustment for smoking habit and critical therapeutic covariates, the HR was 1.07 (95% CI 0.72, 1.61, p = 0.729). At 28 days, VFD were 16 (IQR 0–25) and 25 (IQR 7–26) in the NMBA treatment and control groups, respectively (sub-hazard ratio 0.82, 95% CI 0.67, 1.00, p = 0.055). At 90 days, VFD were 77 (IQR 0–87) and 87 (IQR 0–88) (sub-hazard ratio 0.86 (95% CI 0.69, 1.07; p = 0.177). Conclusions In patients with COVID-19 and moderate-to-severe ARDS, short course of NMBA treatment, applied early, did not significantly improve 90-day mortality and VFD. In the absence of definitive data from clinical trials, NMBAs should be indicated cautiously in this setting.

Prospective assessment of non-reactivity to local anaesthetics is a frequent reason for allergy consultation.To investigate the clinical profiles of subjects referred for allergy evaluation; to prospectively reduce the frequency of evaluation by assessing the persistence, during clinical use, of non-reactivity to contaminant/additive-free mepivacaine; and to determine the usefulness of a diagnostic protocol involving patch testing.In a prospective study, 198 consecutive patients underwent collection of clinical data, skin prick tests and patch tests using allergens/antigens relevant for the investigation, and an intradermal/subcutaneous challenge procedure using contaminant/additive-free mepivacaine, as appropriate. Patients were followed up for 3 years for assessment of non-reactivity persistence using the same diagnostic protocol.Only one-third of the patients had a history of previous adverse local anaesthetic reactions. Absence of sensitization to contaminant/additive-free mepivacaine persisted in all subjects completing the follow-up. Controlled challenge with mepivacaine was negative in 196 patients with both negative specific skin prick tests and patch tests but it was eventful in two subjects with positive specific patch tests. A few subjects displayed positive skin prick tests and/or patch tests for latex and/or additives.A few patients had a relevant history for potential local anaesthetic-induced adverse reactions. Upon assessment of absence of sensitization and reactivity, contaminant/additive-free mepivacaine could safely be given for as long as 3 years. The patch testing was shown to be useful and safe for prediction of challenge outcomes. True allergic reactions to contaminant/additive-free mepivacaine were not observed in our patient series.

SUMMARY Primary windpipe tumour is extremely rare. Squamous cell carcinoma is the most common malignant form, especially in smokers. The radiological appearance of these neoplasms can be classified as intra-luminal, wall-thickening, exophytic form; the majority of the lesions are obstructive in nature and then tend to extra-luminal invasion. This tumour is usually diagnosed late on account of delayed specific symptoms: haemoptysis, dyspnoea, coughing, hoarseness, stridor. Surgery, followed by adjuvant radiotherapy, is the treatment of choice; primary radiotherapy, in inoperable cases, can represent a curative management option. A case of primary tracheal cancer is described and a review of the literature is presented.

Cervicofacial actinomycosis is the most common clinical form of actinomycosis. This bacterial infection is rare. Diagnosis is difficult, often it is definitive only after surgical excision of the cervicofacial mass. Personal experience is reported concerning two cases of cervicoactinomycosis. Diagnosis, in both cases, has been based on histological findings, not on clinical symptoms. A review of the literature shows that mainly males are affected by this condition and, in fact, both patients described here are males. Symptoms of acute infection were absent. Both patients denied any history of oromaxillofacial trauma or recent dental extraction or oral manipulations. Imaging techniques – ultrasonography and computerized tomography – were not effective in making the diagnosis, in either of these patients. Furthermore, fine needle aspiration cytology did not provide a definitive diagnosis. Both patients underwent surgical excision of the mass. Penicillin was the drug of choice in post-operative long-term treatment (one month). In one of the two men, intravenous steroids were administered. As in several reports in the literature, the definitive diagnosis was histological and not clinical.

Laryngocele is a rare, benign dilatation of the laryngeal saccule that may extend internally into the airway or externally through the thyrohyoid membrane. Many laryngoceles are asymptomatic; sometimes they may cause a cough, hoarseness, stridor, sore throat and may present as a swelling on one or both sides of the neck. Laryngocele may be associated with supraglottic squamous cell carcinoma. Computed tomography scan is the most effective imaging method for diagnosis. Surgery is the treatment of choice. A case of large mixed laryngocele in a 75-year-old male is described together with surgical management and follow-up. A review of the literature is also presented.

Since the large multicenter DIG trial has shown no effects of digitalis on the all-cause mortality of patients with chronic heart failure (HF), the broad prescription of this drug in patients with HF appears to be at the very least, questionable. The aims of this study were: to analyze prescription patterns of digitalis, from 1995 to 2000, in a large group of outpatients with HF; to analyze the independent predictors of digitalis prescription and to evaluate the impact of the results of the DIG trial on the prescription rate of this drug.From 1995 to 2000, 11 070 HF outpatients (mean age 64 +/- 12 years, ejection fraction 35 +/- 12%) were enrolled in a large Italian database.Out of 11 070 patients, 7198 (65%) were treated with digitalis. At multivariate analysis, the following variables were independently associated with digitalis prescription; atrial fibrillation (odds ratio [OR] 3.3, 95% confidence interval [CI] 2.9-3.8), ejection fraction30% (OR 1.7, 95% CI 1.5-1.9), NYHA class III-IV vs II-III (OR 1.3, 95% CI 1.2-1.5), admission for HF during the previous year (OR 1.4, 95% CI 1.2-1.5). After the publication of the DIG trial, there was a significant reduction in the rate of digitalis prescription: the percentage of patients taking digitalis fell from 68% in 1996-1997 to 61% in 1998-1999 (p0.001).Over 60% of Italian outpatients with HF were treated with digitalis; as expected, patients with a low ejection fraction, atrial fibrillation and in a more advanced stage of HF are more likely to receive this drug. Finally, after the publication of the DIG trial, the rate of digitalis prescription significantly decreased.

Upper maxillary cysts are a chapter in otorhinolaryngological pathology which have been relatively neglected by the Literature. The reason for this most likely lies in the difficulty in producing a nosographic picture of these pathologies which border on other surgical fields (dentistry, maxillofacial surgery), and because they show significant clinical and etiopathogenic polymorphism. The elements that characterize upper maxillary cysts as a separate clinical entity are basically their cystic nature and origin within the upper maxillary bone, although they can expand widely within the medio-facial region (nasal vestibule, oral vestibule, nasolabial region, palate, maxillary sinus). After having reviewed the various classification schemes proposed over the years, and briefly examining the main clinical and etiopathogenic characteristics and principles for surgical treatment, the present work offers a surgical case study, together with the related iconography. Moreover this work does not neglect embryogenic considerations which are indispensable for the study of some of these pathologies. In this manner the results for 35 surgical procedures on upper maxillary cysts performed from 1989 to 1996 are presented and classified following the Cudennec classification module (1991). This study shows the variety of possible clinical manifestations for these pathologies. Such a variety makes correct diagnosis imperative--today facilitated by modern imaging techniques--and requires diversifying the surgical approach, conditioned not only by the site, extension and nature of the specific lesion, but also by the related symptoms. The significant progress in surgical techniques has made increasingly functional surgery possible and led to the abandonment of such conventional radical techniques as the Caldwell-Luc procedure. Moreover, CT and NMR have provided good image definition, specifying precisely the limits and extensions and, in most cases, facilitating diagnosis of the nature of the disorder with direct and indirect signs of the cystic nature of the lesions whenever the clinical data proves inadequate.

Evaluate the correlations between unstimulated salivary flow, pH and level of S. mutans, analysed through real time PCR, in caries-free and caries-active children.Thirty healthy children were divided into 2 groups: test group (DMFT/dmft ≥ 3 and at least 1 active caries lesion) and control group (DMFT/dmft=0). Un-stimulated saliva was collected, pH was measured and S. mutans and total bacterial amount were evaluated with real-time PCR analysis.Unstimulated salivary flow in the test group was significantly lower (p = 0.0269) compared to group control. The level of S. mutans was higher in the test group (p = 0.176), and an inverse correlation was recorded between total bacterial amount and un-stimulated salivary flow (p = 0.063). In the control group a positive relationship was found between total bacterial amount and S. mutans (p = 0.045) and an inverse correlation between pH and S. mutans (p = 0.088). A t-test and a linear regression analysis were performed.A higher salivary flow and an increased salivary pH seem to represent protective factors against caries in children, while high levels of S. mutans are correlated with caries active lesions. Caries risk assessment should be performed considering all parameters involved in the development of the disease.

Background— Recent studies indicate that T-cell activation may play an important role in the pathophysiology of acute coronary syndromes (ACS). However, although those studies detected T-cell expansion in peripheral blood cells, demonstration of specific T-cell expansion within the plaque of patients with ACS is lacking. The present study aims to address whether a specific, immune-driven T-lymphocyte recruitment occurs within the unstable plaque of patients with ACS. Methods and Results— We simultaneously examined the T-cell repertoire using CDR3 size analysis both in coronary plaques (obtained by directional atherectomy) and in peripheral blood of patients with either ACS (n=11) or chronic stable angina (n=10). Unstable plaques showed a 10-fold increase in T-cell content by quantitative PCR. Using spectratyping analysis, we found several specific T-cell clonotype expansions only in unstable plaque from each patient with ACS, indicating a specific, antigen-driven recruitment of T cells within unstable lesions. Conclusions— For the first time, T-cell repertoire was investigated directly into coronary plaques; using this approach, we demonstrate that coronary plaque instability in the setting of ACS is associated with immune-driven T-cell recruitment, specifically within the plaque.

A subgroup of thymoma patients is affected by severe immunodeficiency clinically resembling an HIV infection (Good syndrome). These individuals are characterized by B lymphopenia with B-lymphopoiesis deficiency. To investigate the pathogenesis of this unique condition, we studied the T-cell repertoire in blood and bone marrow samples by heterogeneity length analysis of CDR3 beta variable regions of the T-cell receptor (spectratyping). While no alterations were found in the peripheral blood, we detected an oligoclonal population of beta variable 8 (BV8) CD8(+) T cells in 5 of 5 bone marrow samples. No lymphocyte expansions were found in the bone marrow of 2 thymoma patients with normal B-cell counts, 2 healthy donors, and 3 patients with diseases unrelated to thymoma. These data suggest that an immune response toward an unknown antigen is taking place in the bone marrow of B-lymphopenic thymoma patients. We propose that BV8 CD8(+) T cells may play a role in the pathogenesis of this immunodeficiency syndrome.

OBJECTIVES Oligoclonal T-cell infiltrates have been detected in the skin of patients with early dcSSc. Peripheral T cells from patients with early dcSSc co-cultured with autologous fibroblasts have been found to expand the same T-cell clonotypes found in the affected skin. Here, we characterize oligoclonally expanded T lymphocytes and investigate functional changes occurring in early-dcSSc co-cultured T lymphocytes and fibroblasts. METHODS Peripheral T lymphocytes from five patients with early (

Summary Background Proteinase-activated receptors (PAR)-2 are members of the family of G-protein-coupled receptors activated by proteases. These receptors are widely expressed in several tissues and in virtually all cells involved in rhinitis and asthma. In particular, proteinases activating PAR-2 may affect airway functions and play a role in human diseases. Objective Assessment of the role of PAR-2 in bronchoconstriction, airway responsiveness and immune response after allergic challenge, in rabbits sensitized to Par j 1, the major allergen of Parietaria judaica pollen. Methods Evaluation of antigen challenge in rabbits treated with PAR-2-activating peptide (PAR-2AP) (SLIGRL) or the scrambled peptide LSIGRL or vehicle immediately before allergen exposure measuring airway responsiveness. Characterization of bronchoalveolar lavage (BAL) following histamine challenge and phenotype analysis of cells by flow cytometry and analysis of cytokine production by quantitative PCR. Results PAR-2AP pre-treatment, but not the scrambled peptide, was able to significantly inhibit bronchoconstriction, airway hyper-responsiveness and to modulate the immune response induced by allergic challenge in sensitized rabbits. The phenotype analysis of the cells recovered from BAL showed an increase in RLA-DR-positive cells while RTLA-positive cells were unchanged. IFN-γ and IL-2 production were inhibited, with a concomitant increase in IL-10 of about 10-fold over the control values. Conclusions In this experimental model, PAR-2 modulates bronchoconstriction interfering with antigen challenge-induced immune response in rabbits sensitized and challenged to Par j 1.

Summary In recent years several reports have suggested that T cells may have a role in systemic sclerosis (SSc). The aim of our study was to investigate the dynamics of T cell repertoire in early SSc disease analysing a target organ, the skin, and the peripheral blood. To date, indeed, it is not clear if T cell expansions found in SSc reflect a general activation or result from specific antigen stimulation in the target organs. This is an important point to assess in order to characterize the role of T cells in the development of SSc. To address these questions we studied T cell repertoire by CDR3 length analysis in skin biopsies and peripheral blood obtained from patients affected by SSc and we found that a skewed T cell repertoire was present only in the biopsies. In order to characterize more effectively the meaning of these data, we performed co-cultures using fibroblasts and peripheral blood mononuclear cells (PBMCs) obtained from SSc patients. These experiments showed that same T cell expansions were detectable in the skin of SSc patients and in the cultures of PBMCs and autologous fibroblasts of the patients but not in their peripheral blood. Taken together, these data suggest that fibroblasts trigger specific T cell expansions in the early phase of SSc.

Background: The outcome of patients with nasopharyngeal carcinoma (NPC) presenting as advanced-stage disease or failing conventional radio-chemotherapy is poor. Thus, additional forms of effective, low-toxicity treatment are warranted to improve NPC prognosis. Since NPC is almost universally associated with Epstein– Barr virus (EBV), cellular immunotherapy with EBV-specific cytotoxic T lymphocytes (CTLs) may prove a successful treatment strategy. Patient and methods: A patient with relapsed NPC, refractory to conventional treatments, received salvage adoptive immunotherapy with EBV-specific CTLs reactivated ex vivo from a human leukocyte antigen-identical sibling. EBV-specific immunity, as well as T-cell repertoire in the tumor, before and after immunotherapy, was evaluated. Results: CTL transfer was well tolerated, and a temporary stabilization of disease was obtained. Moreover, notwithstanding the short in-vivo duration of allogeneic CTLs, immunotherapy induced a marked increase of endogenous tumor-infiltrating CD8+ T lymphocytes, and a long-term increase of latent membrane protein 2-specific immunity. Conclusions: Preliminary data obtained in this patient indicate that EBV-specific CTLs are safe, may exert specific killing of NPC tumor cells in vitro, and induce antitumor effect in vivo.

The aim of the present prospective investigation was to study 49 dyspeptic Helicobacter pylori (HP)-positive (HP+) or -negative (HP), CagA+ and CagA- patients with a normal pattern or pure chronic gastritis at initial histology as well as normal features or hyperemic gastropathy at initial endoscopy in a two-year follow up. All the HP+ patients were treated with omeprazole 20 mg twice a day plus amoxicillin 1 g twice a day for two weeks. No substantial change was seen in gastritis in CagA+ patients in whom the infection was not eradicated, and, in contrast, a progressive improvement in 13/14 successfully treated patients was found. At endoscopy, a progressive change to a normal picture was seen in 8 and no change in 6 of 14 patients whose HP infection was eradicated, in contrast a worsening in the 9 HP+ patients who were still infected was observed. In particular, peptic lesions arose in 6 of 21 CagA+ patients in whom the infection was not eradicated. In conclusions, the lack of change in chronic gastritis at histology and the progressive worsening of endoscopic hyperemic gastropathy (with peptic lesions arising in 28,6%) when HP+ CagA+ infection is not eradicated, unlike the progressive improvement of the anatomoclinical condition in the patients whose infection was eradicated, draws attention to the relevance of eradicating HP in CagA+ patients even when no peptic lesion is found at initial endoscopy.

The role of Tetranychus urticae (TU) as an occupational allergen has thus far been investigated only in selected farmer samples.The prevalence of TU-induced sensitization and occupational diseases in a randomized sample of farmers living in a temperate climate area was investigated. Occupational/nonoccupational symptoms, skin prick test (SPT) results with common allergens and TU, specific occupational test results, and greenhouse or open-field sources of TU exposure were assessed. The study design was cross-sectional.The prevalence of positive SPT to TU was 6%. TU-induced allergic/nonallergic complaints accounted for 65% of farmers with challenge-confirmed occupational disease. In all farmers, sensitization to common allergens was a risk factor for both current occupational and nonoccupational complaints, while TU sensitization was a prominent risk factor for occupational complaints. Furthermore, in SPT-positive farmers, only the presence of seasonal occupational complaints was significantly associated with TU sensitization. Common allergen sensitization was a risk factor for development of TU sensitization, which was more frequent in greenhouse than in open-field workers.TU was a common nontraumatic, allergic occupational hazard for farmers. Since occupational seasonal symptoms could be directly related to the presence of TU sensitization, allergy to this mite should be routinely investigated in farmers.

The aim of this study was to assess the protective effect and the safety profile of amifostine in 16 esophageal cancer patients undergoing neoadjuvant chemo-radiation therapy (group A) compared to 21 matched patients (group B), treated with the same schedule without receiving amifostine, and considered as controls. Haematological and extra-haematological toxicity were evaluated according to WHO criteria and considered as result of amifostine activity. The bone marrow toxicity was globally lower in group A than in group B. We recorded 4 cases of mucosities in group B compared to 1 case in group A. amifostine-related side effects were few (2 cases of hypotension and 1 of vomiting), mild, and well controlled. In conclusion, amifostine seems to be effective and safe when used as protective agent also in esophageal cancer.