Secondary pneumomediastinum in COVID-19 patient: A case managed with VV-ECMO.

Air leak syndrome, including pneumomediastinum (PM), pneumopericardium, pneumothorax, or subcutaneous emphysema, is primarily caused by chest trauma, cardiothoracic surgery, esophageal perforation, and mechanical ventilation. Secondary pneumomediastinum (SP) is a rare complication, with a much lower incidence reported in patients with coronavirus disease 2019 (COVID-19). Our patient was a 44-year-old nonsmoker male with a previous history of obesity (Body Mass Index [BMI] 35 kg/m2), hyperthyroidism, hypokinetic cardiopathy and atrial fibrillation in treatment with flecainide, who presented to the emergency department with 6 days of fever, cough, dyspnea, and respiratory distress. The COVID-19 diagnosis was confirmed based on a polymerase chain reaction (PCR) test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). After initiation of mechanical ventilation, a chest computed tomography (CT) on the first day revealed bilateral multifocal ground-glass opacities, consolidation and an extensive SP and pneumoperitoneum. Our therapeutic strategy was initiation of veno-venous extracorporeal membrane oxygenation (VV-ECMO) as a bridge to recovery after positioning 2 drains (mediastinal and pleural), for both oxygenation and carbon dioxide clearance, to allow protective and ultra-protective ventilation to limit ventilator-induced lung injury (VILI) and the intensity of mechanical power for lung recovery. After another chest CT scan which showed a clear reduction of the PM, 2 pronation and neuromuscular relaxation cycles were also required, with improvement of gas exchange and respiratory mechanics. On the 15th day, lung function recovered and the patient was then weaned from VV-ECMO, and ultimately made a good recovery and was discharged. In conclusion, SP may be a reflection of extensive alveolar damage and should be considered as a potential predictive factor for adverse outcome in critically ill SARS-CoV2 patients.

Anaphylaxis in elderly people.

PURPOSE OF REVIEW: Anaphylaxis is common in old-age adults but is insufficiently understood by physicians, and may be underdiagnosed. This review discusses the specificities of anaphylaxis in this age group and stresses the importance of adrenaline in its management. RECENT FINDINGS: Data from the European Anaphylaxis Registry on elderly patients is a major finding. Other findings include the prevention of possible anaphylactic reactions in coronavirus disease 2019 vaccination as well as some new epidemiologic data. SUMMARY: The most common risk factors are hymenoptera venom and food and drug allergy. Cardiovascular symptoms are the most important ones to reverse in old-age adults, especially due to the multiple comorbidities. Anaphylaxis in old-age adults has a more severe outcome than in younger ones. Polypharmacy is a specific factor to be considered. The Airway, Breathing, Circulation, Disability, Exposure (ABCDE) algorithm is applicable in all clinical emergencies for immediate assessment and treatment, and should be considered for all patients. Adrenaline is the mainstay of the management of the condition. There are no absolute contraindications to the prescription of self-injectable adrenaline in elderly individuals at risk of anaphylaxis.

Delirium incidence and risk factors in patients undergoing non-invasive ventilation for acute respiratory failure: a multicenter observational trial.

BACKGROUND: Noninvasive ventilation (NIV) still has high failure rate when used for de novo acute respiratory failure (ARF). Delirium may impact the outcome, however data regarding its incidence, timing of occurrence and clinical predictors in this subset of patients are scarce. METHODS: Consecutive patients with de novo ARF subjected to NIV were recruited in 10 Italian Respiratory Intensive Care Units (RICUs) and Intensive Care Units (ICUs). Demographics and clinical features, including tolerance to interface and NIV setting were recorded on admission and during stay, whereas delirium onset and type was assessed by the Confusion Assessment Method for ICU (CAM-ICU)-7 scale and Richmond Agitation Sedation Scale (RASS) twice/per day up to a week. The association between clinical variables and the occurrence of delirium and its influence on NIV failure and other clinical outcomes were analyzed. RESULTS: Thirty-two out of 90 enrolled patients (36%) developed delirium over seven days upon admission; median time to onset was 48 hours (24-60). Older age (OR=2.7 [1.9-9], P=0.01), the presence of cancer OR=3.7 [2-5.4], P=0.002), sepsis (OR=1.7 [1.1-3.4], P=0.01), SOFA Score (OR=1.8 [1.1-3.1], P=0.01), low tolerance to interface (OR=3.2 [2.1-5], P=0.002), use of helmet (OR=1.9 [1.2-4.3] P=0.04), and higher PRE-DELIRIC (OR=3.5 [1.3-15], P=0.03) and BORG (OR=1.7 [1.1-4.6], P=0.02] scores were significantly associated with delirium. Delirium had high risk for NIV failure (HR=3.5 95% CI: [1.4-8.6], P=0.0002) and it significantly associated with longer RICU/ICU stay and higher mortality. CONCLUSIONS: Delirium onset in acute hypoxic patients undergoing NIV is frequent and negatively affects the outcome. Multiple related clinical factors should be addressed early on admission to prevent the delirium-related risk of NIV failure in these patients.

Orofacial granulomatosis: Clinical and therapeutic features in an Italian cohort and review of the literature.

BACKGROUND: Orofacial granulomatosis (OFG) is characterized by granulomatous inflammation of the soft tissues of maxillofacial region. We explored OFG patients from 10 different Italian centers and summarized the most recent literature data. METHODS: A review of patients with OFG was carried out. An extensive online literature search was performed to identify studies reporting diagnosis and management of OFG. RESULTS: Thirty-nine patients were recruited between January 2018 and February 2020. Most of them (97.4%) displayed involvement of the lips, and 28.2% suffered from Melkersson-Rosenthal syndrome. Two patients received diagnosis of CD and one patient of sarcoidosis, suggesting secondary OFG. Oral aphthosis and cervical lymphadenopathy were also described. The mean diagnostic delay was 3.4 years. Histological evaluation was performed in 34/39 patients (87.2%); non-caseating granulomas were found in 73.5% of them. Neurological symptoms (28.2%), gastrointestinal symptoms in absence of overt inflammatory bowel disease (IBD) (20.5%), and atopy (35.9%) were also identified. Therapeutic approaches varied among the centers. Steroids (51.3%) were used with good or partial results. Anti-TNF-α and anti-IgE monoclonal antibodies were used in 6 (15.4%) and 1 (2.6%) patients, respectively, with variable results. Surgery was the choice for 2 patients with good response. CONCLUSIONS: OFG is a rare and neglected disease showing multiple clinical phenotypes. While early diagnosis is crucial, management is difficult and highly dependent on the expertise of clinicians due to the lack of international guidelines. There is a need to establish registry databases and address challenges of long-term management.

Tryptase values in anaphylaxis and insect allergy.

PURPOSE OF REVIEW: To recognize the relevance of serum tryptase measurement as a useful tool for the diagnosis of allergic diseases and mast cell disorders. RECENT FINDINGS: Recent data on the role of mast cells and tryptase in allergic and other diseases provide new understanding into the mechanisms and causes of anaphylaxis. SUMMARY: Measurement of transiently elevated tryptase levels shortly after a severe reaction can help elucidate mechanism behind the reaction in identifying mast cell activation. Hymenoptera venom allergy represents an important cause of morbidity and mortality worldwide. Venom allergy is a typical IgE-mediated reaction because of sensitization to one or more allergens of the venom, and accounts for 1.5-34% of all cases of anaphylaxis. There is a preferential association between insect venom allergy and mastocytosis. The diagnosis of a clonal mast cell disease leads to therapeutic consequences concerning the treatment of venom allergy. In conclusion, baseline tryptase levels support the clinical diagnosis of anaphylaxis and mast cell disorders, determine venom immunotherapy treatment and are relevant in deciding on lifelong treatment.

Anaphylactic Reactions After Discontinuation of Hymenoptera Venom Immunotherapy: A Clonal Mast Cell Disorder Should Be Suspected.

BACKGROUND: Up to 75% of patients with severe anaphylactic reactions after Hymenoptera sting are at risk of further severe reactions if re-stung. Venom immunotherapy (VIT) is highly effective in protecting individuals with ascertained Hymenoptera venom allergy (HVA) and previous severe reactions. After a 3- to 5-year VIT course, most patients remain protected after VIT discontinuation. Otherwise, a lifelong treatment should be considered in high-risk patients (eg, in mastocytosis). Several case reports evidenced that patients with mastocytosis and HVA, although protected during VIT, can re-experience severe and sometimes fatal reactions after VIT discontinuation. OBJECTIVE: To evaluate whether patients who lost protection after VIT discontinuation may suffer from clonal mast cell disorders. METHODS: The survey describes the characteristics of patients who received a full course of VIT for previous severe reactions and who experienced another severe reaction at re-sting after VIT discontinuation. Those with a Red Española de Mastocitosis score of 2 or more or a serum basal tryptase level of more than 25 ng/mL underwent a hematological workup (bone marrow biopsy, KIT mutation, expression of aberrant CD25) and/or skin biopsy. RESULTS: Nineteen patients (mean age, 56.3 years; 89.5% males) were evaluated. All of them had received at least 4 years of VIT and were protected. After VIT discontinuation they were re-stung and developed, in all but 1 case, severe anaphylactic reactions (12 with loss of consciousness, in the absence of urticaria/angioedema). Eighteen patients (94.7%) had a clonal mast cell disorder, 8 of them with normal tryptase. CONCLUSIONS: Looking at this selected population, we suggest that mastocytosis should be considered in patients developing severe reactions at re-sting after VIT discontinuation and, as a speculation, patients with mastocytosis and HVA should be VIT-treated lifelong.

Clinico-pathological and biomolecular findings in Italian patients with multiple cutaneous neurofibromas.

BACKGROUND: Neurofibroma occurs as isolated or multiple lesions frequently associated with neurofibromatosis type 1 (NF1), a common autosomal dominant disorder affecting 1 in 3500 individuals. It is caused by mutations in the NF1 gene, which comprises 60 exons and is located on chromosome 17q11.2. NF1 is a fully penetrant gene exhibiting a mutation rate some 10-fold higher compared with most other disease genes. As a consequence, a high number of cases (up to 50%) are sporadic. Mutation detection is complex due to the large size of the NF1 gene, the presence of pseudogenes and the great variety of lesions. METHODS: 110 patients with at least two neurofibroma lesions recorded in the files of the Pathology Department of the University of Modena during the period 1999-2010, were included in this study. Through interviews and examination of clinical charts, pedigrees were drawn for all patients who were affected by at least two neurofibromas. We attempted to delineate the clinical features of NF1 and the mutational spectrum in the cohort of 11 NF1 families identified. For each proband, the whole coding sequence and all splice sites were studied for mutations, either by the protein truncation test (PTT), or, more frequently, by denaturing high performance liquid chromatography (DHPLC). Two GIST tumors of NF1 patients were tested for somatic NF1 mutations. RESULTS: NF1 germline mutations were identified in 7 (68%) patients. A novel mutation, c.3457_3460delCTCA in exon 20, was detected in two unrelated patients and was associated with different clinical features. No NF1 somatic mutations were detected in the GIST tumors. A wide phenotypic and genotypic variability was registered, both in the spectrum of skin lesions and visceral neoplasms, even among members of the same family who had different clinical manifestations. A proclivity to multiple tumors arising in the same subject, and a higher tumor burden per family were the most relevant findings observed in patients affected with the NF1 mutation. CONCLUSIONS: We report a novel NF1 mutation and we contribute data for the refinement of the NF1 genotype-phenotype spectrum.

Gastrointestinal stromal tumor and other primary metachronous or synchronous neoplasms as a suspicion criterion for syndromic setting.

Gastrointestinal stromal tumors (GISTs) may be sporadic or inherited. Although KIT and PDGFRA activating mutations are the oncogenic mechanisms in most sporadic and inherited GISTs, a small subset of GISTs are negative for both. Besides the classical Familial GIST Syndrome, GIST can occur as part of multi-neoplastic disease. The present study was designed to analyze the synchronous and metachronous tumors developed among GIST patients assessed by our institution for GIST Syndrome setting recognition. Patients (n=141) with primary GIST (77 men and 64 women) were recruited between 1988 and 2007 and their clinical and pathological records were reviewed. Mutation analysis of KIT, PDGFRA, NF1 and MMR genes was performed on somatic and peripheral blood DNA. GISTs occurred associated with other primary malignancies in 46 of 141 (32.6%) patients. The most common neoplasms were gastrointestinal and genitourinary. A novel exon 6 germline large deletion of NF1 was identified in the NF1/GIST kindred. The development of GIST associated with other neoplasms is common and diagnosis of peculiar benign associated-neoplasms warrants the search for familial cancer susceptibility. In particular, syndromic or familial settings have to be suspected in the presence of neurofibroma or lung chordoma in C-KIT and PDGFRA negative GIST patients.