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Spontaneous pneumomediastinum (SPM) is a rare clinical entity that concerns mainly young adults. We report 13 cases (11 males/2 females) of SPM. The average age was 31 ± 0.85 years. The most common precipitating factor was asthma attack. The onset symptoms were mainly chest pain (11 cases). Synchronous pneumothorax was found in 5 cases and it was bilateral in 2 patients. The evolution was marked by the spontaneous resorption. SMP is an underrecognized cause of chest pain in young adults. Chest radiography is usually sufficient for the diagnosis, and further diagnostic procedures are generally not necessary. The prognosis is often favorable.

Therapeutic nucleic acids (TNAs) comprise an alternative to conventional drugs for cancer therapy. Recently, stable nucleic acid lipid particles (SNALPs) have been explored to deliver TNA efficiently and safely both in vitro and in vivo. Small interfering RNA (siRNA) and messenger RNA (mRNA) based drugs have been suggested for a wide range of pathologies, and their respective lipid nanoparticle (LNP) formulations have been optimised using a Design of Experiments (DoE) approach. However, it is uncertain as to whether data obtained from DoE using simple experimental outputs can be used to generate a general heuristic for delivery of diverse TNA both in vitro and in vivo. Using plasmid DNA (pDNA), for which limited DoE optimisation has been performed, and siRNA to represent the two extremities of the TNA spectrum in terms of size and biological requirements, we performed a comparative DoE for both molecules and assessed the predictive qualities of the model both in vitro and in vivo. By producing a minimum run of 24 SNALP formulations with different lipid compositions incorporating either pDNA or siRNA, DoE models were successfully established for predicting the effect of individual lipid composition on particle size, TNA encapsulation and transfection both in vitro and in vivo. The results showed that the particle size, and in vitro and in vivo transfection efficiency of both pDNA and siRNA SNALP formulations were affected by lipid compositions. The encapsulation efficiency of pDNA SNALPs but not siRNA SNALPs was affected by the lipid composition. Notably, the optimal lipid compositions of SNALPs for pDNA/siRNA delivery were not identical. Furthermore, in vitro transfection efficiency could not be used to predict promising LNP candidates in vivo. The DoE approach described in this study may provide a method for comprehensive optimisation of LNPs for various applications. The model and optimal formulation described in this study can serve as a foundation from which to develop other novel NA containing LNPs for multiple applications such as NA based vaccines, cancer immunotherapies and other TNA therapies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Rational: Tumor immunogenic cell death (ICD), induced by certain chemotherapeutic drugs such as doxorubicin (Dox), is a form of apoptosis potentiating a protective immune response. One of the hallmarks of ICD is the translocation of calreticulin to the cell surface acting as an 'eat me' signal. This manuscript describes the development of a stable nucleic acid-lipid particles (SNALPs) formulation for the simultaneous delivery of ICD inducing drug (Dox) with small interfering RNA (siRNA) knocking down CD47 (siCD47), the dominant 'don't eat me' marker, for synergistic enhancement of ICD. Methods: SNALPs loaded with Dox or siCD47 either mono or combinatory platforms were prepared by ethanol injection method. The proposed systems were characterized for particle size, surface charge, entrapment efficiency and in vitro drug release. The ability of the SNALPs to preserve the siRNA integrity in presence of serum and RNAse were assessed over 48 h. The in vitro cellular uptake and gene silencing of the prepared SNALPs was assessed in CT26 cells. The immunological responses of the SNALPs were defined in vitro in terms of surface calreticulin expression and macrophage-mediated phagocytosis induction. In vivo therapeutic studies were performed in CT26 bearing mice where the therapeutic outcomes were expressed as tumor volume, expression of CD4 and CD8 as well as in vivo silencing. Results: The optimized SNALPs had a particle size 122 ±6 nm and an entrapment efficiency > 65% for both siRNA and Dox with improved serum stability. SNALPs were able to improve siRNA and Dox uptake in CT26 cells with enhanced cytotoxicity. siCD47 SNALPs were able to knockdown CD47 by approximately 70% with no interference from the presence of Dox. The siCD47 and Dox combination SNALPs were able to induce surface calreticulin expression leading to a synergistic effect on macrophage-mediated phagocytosis of treated cells. In a tumor challenge model, 50% of mice receiving siCD47 and Dox containing SNALPs were able to clear the tumor, while the remaining animals showed significantly lower tumor burden as compared to either monotreatment. Conclusion: Therefore, the combination of siCD47 and Dox in a particulate system showed potent anti-tumor activity which merits further investigation in future clinical studies., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Introduction: the use of invasive mechanical ventilation (IMV) in acute exacerbations of chronic obstructive pulmonary disease (AECOPD) constitutes a negative turning point in the progression of the disease. The purpose of this study is to determine factors predicting the need for IMV in AECOPD., Methods: we conducted a retrospective study by reviewing the medical records of patients with AECOPD hospitalized in our Department over a 18-year period (2000-2017). We compared 2 groups: G1: patients with AECOPD undergoing at least one IMV and G2: patients who had never undergone IMV following AECOPD., Results: the study included 1152 patients with COPD: 133 in the G1 group (11.5%), and 1019 in the G2 group (88.5%). G1 patients were more symptomatic (p < 0.001), with more severe bronchial obstruction (p < 0.001). G1 patients had more exacerbations (p < 0.001), more hospitalizations and a higher need for non-invasive ventilation (NIV) (p < 0.001). Similarly, G1 patients more often developed chronic respiratory failure (p < 0.001) and had significantly lower survival rates. Independent risk factors associated with IMV were hypercapnia and decreased pH (in patients with severe AECOPD), a history of NIV, and chronic respiratory failure (CRF)., Conclusion: respiratory function impairment, the severity of exacerbation and the need for NIV in a previous episode are factors predicting the need for IMV and poor outcomes., Competing Interests: Les auteurs ne déclarent aucun conflit d´intérêts., (Copyright: Lobna Loued et al.)

Introduction: smoking is the leading risk factor for chronic obstructive pulmonary disease (COPD). Disease evolution is characterized by the occurrence of acute exacerbations (AE). The purpose of our study is to assess the effect of intensity of smoking intoxication (in packs-years (PAs)) on the different severity parameters of AE in smoking patients with COPD treated in hospital., Methods: we conducted a retrospective, monocentric study of 685 smoking patients with COPD who had been hospitalized at least once for an AE between 1990 and 2017. Patients were divided into 2 groups (G1: < 30PA, and G2: ≥ 30PA). The different severity parameters of COPD AE were compared between the two groups., Results: the average age of our patients was 66 years. There were no significant differences between the two groups with respect to the severity of biologic inflammatory syndrome, length of stay in hospital and antibiotic treatment duration. G2 was characterized by lower PaO2 levels during AE (G1: 63.5, G2: 59.3, p: 0.007), longer length of stay in the emergency department (p < 0,001), increased use of non-invasive ventilation (p: < 0.001) and invasive ventilation (p: 0,008). G2 had more EA/year (G1: 2.06. G2: 2.72/patient/year, p: 0.001) with a shorter mean time for severe AE (p: 0.038). Conclusion: the intensity of smoking intoxication has a negative impact on several severity parameters of severe COPD EAs. Hence the role of smoking cessation in preventing this disease and its complications., Competing Interests: Les auteurs ne déclarent aucun conflit d´intérêts., (Copyright: Ahmed Ben Saad et al.)

Background: We aimed to describe the episodes and trends of admissions for community-acquired Respiratory Infections (RI) over a 12-year period and to assess the impact of Haemophilus influenza type b (Hib) vaccine on RI admissions in children aged up to 3 years., Methods: We conducted a twelve-year retrospective observational study on all community-acquired RI admitted to Fattouma Bourguiba Hospital in Monastir Governorate (Tunisia) from 1 January 2002 to 31 December 2013. RI cases were selected from the Regional Registry of Hospital Morbidity. Data were coded according to ICD-10. To assess the impact of the Hib vaccine, three cohorts were defined based on vaccine status (unvaccinated cohort, first vaccinated cohort (VC) by monovalent form and second VC by pentavalent combination)., Results: Admissions for RI represented 17.6% (CI95%: 17.3-18.1) of all communicable diseases hospitalizations (n = 6 061/34 289). The crude incidence rates (CIR) per 100,000 inh were 24.2 for upper RI (URI) and 77.5 and for Lower RI (LRI) (p < 0.0001). Pneumonias represented 53.9% of LRI. Sex-ratio (male/female) was 1.12 for URI and 1.64 for LRI (p < 0.0001). At admission, the median age was 22 years (IQR: 3-52). Admission for Pneumonia increased significantly during study period (slope 'b' = 5.16; p < 0.0001) especially in children up to 5 years old (slope 'b' = 5.53) and in elderly (slope 'b' = 2.13). Among children up to 3 years old, the CIRs per 100,000 for Hib pneumonia admission were 11.6 in Non-Vaccinated Cohort (NVC), 10.6 in Vaccinated Cohort (VC) by protocol 1 (Hib Vaccine monovalent) and 0.80 in VC by protocol 2 (pentavalent vaccine combination).The relative risk reduction was 99% for protocol 2 (p < 0.001)., Conclusion: Admissions for RI in a  tertiary level hospital were common with an increasing trend. The Hib immunization program, in particular the pentavalent combination, has had a positive impact on the reduction of related acute diseases.

Introduction: bronchial dilations (BDs) seem to have a major role in the natural history of chronic obstructive pulmonary disease (COPD). The purpose of our study was to evaluate the impact of BDs on the severity and progression of COPD as well as on patients' prognosis., Methods: we conducted a retrospective, single-center, analytical study over the period 1995- 2017. The study was based on data from the medical records of patients with COPD who had undergone chest CT scan during the follow-up period. We compared two groups (G) of patients: G1: COPD with BDs; G2: COPD without BDs., Results: our study included 466 patients with COPD. Among them 101 (21.6%) had BDs associated with COPD. G1 patients had lower maximum expiratory volume in the first second (FEV1) (G1: 1.21 L, G2: 1.37 L, p = 0.015), lower forced vital capacity (FVC) (p = 0.014), a lower PaO2 at steady state (p = 0.049), a higher rate of acute exacerbations (AE) per year (G1: 3.31, G2: 2.44, p = 0.001) and a higher rate of hospitalizations in the Intensive Care Unit per year (p = 0.02). G1 patients with AE receiving treatment in hospital had lower PaO2 3) on admission (G1: 60 mmHg, G2: 63.7 mmHg, p = 0.02 G2: 63.7 mmHg, p = 0.023), more elevated carbon dioxide (CO2) levels (p = 0.001) and were characterized by a higher use of non-invasive ventilation (NIV) (p = 0.044) and invasive mechanical ventilation (p = 0.011). G2 patients had better overall survival (p = 0.002)., Conclusion: bronchial dilatations are an indicator of poor prognosis in patients with chronic obstructive pulmonary disease, expecially because of the higher rate and severity of exacerbations, airway obstructions and mortality., Competing Interests: Les auteurs ne déclarent aucuns conflits d'intérêts, (Copyright: Ahmed Ben Saad et al.)

Haemoptysis is a frequently occurring but sometimes life-threatening condition. Congenital cardiovascular abnormalities are rare causes of haemoptysis. We report a case of a 33-year-old man without any past medical history complaining of haemoptysis with no other associated clinical manifestations. A contrast-enhanced chest computed tomography scan revealed aortic coarctation with dilation of the internal mammary, intercostal and bronchial arteries. He underwent stent placement after balloon angioplasty with favourable outcomes., Learning Points: Adult patients with congenital cardiovascular abnormalities such as aortic coarctation may rarely, due to the high pressure and dilation in the bronchial arteries, present with recurrent haemoptysis as the sole clinical sign.A multidetector computed tomography scan contributes significantly to the aetiological diagnosis of haemoptysis in cases of congenital cardiovascular abnormalities.Interventional procedures such as stenting are currently the preferred approach for the treatment of aortic coarctation in adults, with good outcomes., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests., (© EFIM 2020.)

Introduction: the relationship between computed tomography (CT) scan findings and the risk of recurrence of primary spontaneous pneumothorax (PSP) is controversial. The purpose of this study is to determine the relationship between the Dystrophy Severity Score (DSS) and PSP recurrence after an initial episode., Methods: we conducted a retrospective study including patients admitted to the hospital with PSP (first episode) between 2005-2017. The study population was divided into 2 groups, G1: PSP recurrence, G2: No recurrence. We undertook univariate analysis including various variables such as the DSS score followed by multivariate analysis., Results: eighty-six patients were included in this study. Forty-eight percent of cases had PSP recurrence. Although the DSS score was significantly associated with PSP recurrence (p=0.008), multivariate analysis showed that the presence of bubbles on chest CT scan was the independent risk factor associated with PSP recurrence after a first episode (risk report: 3.26, p < 0.008)., Conclusion: the risk of PSP recurrence is significantly associated with the presence of bubbles on chest CT scan. Further studies are needed for better assessment of the DSS score., Competing Interests: Les auteurs ne déclarent aucun conflit d’intérêts., (© Ahmed Ben Saad et al.)

Introduction: chronic obstructive pulmonary disease (COPD) has been frequently associated with co-morbidities. The purpose of our study is to analyze the impact of co-morbidities on the progression and prognosis of COPD., Methods: we conducted a retrospective study of patients with COPD hospitalized and/or followed up in the Department of Pneumology at the Fattouma Bourguiba University Hospital in Monastir over the period January 2000-December 2017. The patients were initially divided into two groups, the G0 group (isolated COPD) and the G1 group (with at least one comorbidity). Patients in the G1 group were divided in two subgroups: A group (patients with 1-2 co-morbidities) and B group (≥ 3 comorbidities associated). Different parameters of COPD severity were compared between the different groups., Results: a total of 1152 patients with COPD were enrolled. Seventy-nine percent of patients had at least a chronic disease associated with COPD. The presence of at least one co-morbidity was associated with an increase in the number of severe exacerbations (p = 0.004), in the use of Long-term oxygen therapy (p = 0.006) and with reduced survival (p = 0.001). Similarly, a greater number of co-morbidities (≥ 3 co-morbidities) were associated with more severe systemic inflammation, more frequent use of mechanical ventilation or non-invasive ventilation (p=0.04) and reduced survival (p = 0.05)., Conclusion: the presence of co-morbidities in patients with COPD is associated with higher severity and poorer prognosis., Competing Interests: Les auteurs ne déclarent aucun conflit d’intérêts., (© Ahmed Ben Saad et al.)

Introduction: Obesity and asthma are two chronic diseases affecting millions of people around the world. A causal relationship has been suggested. The purpose of our study is to examine the profile in obese people with asthma and to determine the relationship between the different severity parameters in asthma and the degree of obesity., Methods: We conducted a retrospective, monocentric, analytical study involving 450 asthmatics with a body mass index (BMI) ≥ 30 kg/m 2 having follow up visit at less than 6 months. The study was conducted in the Department of Pneumology and Allergology at the Fattouma Bourguiba Hospital in Monastir., Results: The average age at diagnosis was 45±12.8 years. Mean BMI was 34.8±4.2 kg/m 2 . Asthma was well-controlled in 55.3% of patients. Severity criteria were reported in 37.4% of cases. According to GINA 2016, 24.2% of patients received treatment at step 4. Two asthma phenotypes associated with obesity were reported. The first phenotype (52.4%) was characterized by early-onset asthma associated with a higher incidence of allergic disease and manifestations of atopy. The second phenotype (47.6%) was characterized by late onset asthma, commonly occurring in female sex as well as a higher rate of comorbidities and hospitalizations. Patients with class II and III obesity had significant ventilatory deficiency (CVF: p = 0.002 and FEV1: p = 0.007)., Conclusion: Obesity is one of the key factors involved in poor asthma control. Its management, which has not yet been codified, should be multidisciplinary., Competing Interests: Les auteurs ne déclarent aucun conflit d’intérêts., (© Saousen Cheikh Mhamed et al.)

Introduction: Non-small cell lung cancer (NSCLC) is a public health problem that usually affects the elderly. Currently and for some years now, this disease is increasingly affecting the young population. The purpose of this study was to analyze the features of NSCLC in young subjects and to assess survival as well as the various prognostic factors., Methods: We conducted a retrospective study of all patients under the age of 50 years treated in the Department of Pneumology at the Fattouma Bourguiba University Hospital, Monastir for NSCLC. Survival and prognostic factors have been analyzed according to Kaplan Meier method., Results: The average age of patients was 43.8 ± 5.29 years. The most common histological type was lung adenocarcinoma (66.1%). NSCLC was discovered at an advanced or metastatic stage in 79.7% of cases. The median overall survival was 8 ± 0.72 months. Univariate analysis showed that survival was significantly influenced by patients' general status, assessed according to the "Performance Status (PS)" index of the World Health Organization on admission, tumor stage and CRP concentrations. Multivariate analysis was performed, which enabled us to use PS index ≥ 2 and high CRP concentrations as factors of poor prognosis., Conclusion: Despite the therapeutic progress, prognosis in young subjects with NSCLC is poor. Early diagnosis and management can improve survival in these patients., Competing Interests: Les auteurs ne déclarent aucun conflit d’intérêts., (© Samah Joobeur et al.)

Introduction: There is a controversy over the relationship between blood eosinophil count (BEC) and the severity of chronic obstructive pulmonary disease (COPD) exacerbations. The purpose of our study was to determine the relationship between blood eosinophil count and multiple parameters in assessing the severity of serious acute exacerbation (AE) of obstructive pulmonary disease., Methods: We conducted a retrospective monocentric study of hospitalized patients with obstructive pulmonary disease treated between 2005 and 2015. We compared 2 groups of patients: G1(BEC+): BEC ≥ 200 cell/μl (103 cases, 20.4%), G2(BEC-): BEC < 200 cell/μl (403 patients: 79.6%)., Results: A total of 506 subjects with obstructive pulmonary disease were included in the study. No significant difference between the two groups in age, gender, forced expiratory volume in one second (FEV1), and the number of AE/year (BEC+: 2.6, BEC-:2.5 AE/year; p = 0.48) was found. The analysis of the parameters of severity of serious AE showed no difference between the two groups in partial pressure of oxygen PaO2 measured on admission (60.5, 59.2 mmHg; p = 0.26), capnia (p=0.57), pH (p=0.74), C-reactive protein rate (mg/L) (82.7, 81; p = 0.89), leukocytosis (p = 0.36), non-invasive mechanical ventilation (5.8%, 6.5%; p = 0.81), invasive mechanical ventilation (p = 0.5),length of stay in hospital (9.7, 9 days; p = 0.21), mean time to next AECOPD (p = 0.32). Survival at 1 year was comparable between the two groups (94% vs 96%; Log Rank: 0.708)., Conclusion: Increased BEC in patients with COPD does not appear to have a negative effect on patients with severe AE. Despite the recent guidelines recommend to consider blood eosinophil count while making treatment decisions, the role and the prognostic interest of blood eosinophil count in patients with COPD could be population-dependent., Competing Interests: Les auteurs ne déclarent aucun conflit d'intérêts., (© Ahmed Ben Saad et al.)