Home Use of Mechanical Insufflation/Exsufflation in Adult Patients in Western Switzerland.

BACKGROUND: Mechanical insufflation/exsufflation (MI-E) devices are often prescribed to patients with inefficient cough and recurrent infections, but their use in the home setting is not well characterized. OBJECTIVE: The objective of this study was to report a real-life experience and identify factors that are associated with home MI-E use in adult patients. METHODS: This is a cross-sectional observational study of adult subjects with neurological disease using MI-E at home for more than 3 months. RESULTS: A total of 43 patients were included. Median age (interquartile range) was 48 (31-64) years. The most common diagnosis was muscular dystrophy (n = 15), followed by multiple sclerosis (n = 7) and amyotrophic lateral sclerosis (n = 7). 24 subjects (56%) reported using the MI-E at least once weekly. Based on device data downloads, the median objective use was 23% of days analysed (approximately 2 times per week). The vast majority (94%) of all participants reported using the device at least daily during an infectious episode, while 62% reported having used the device in emergency situations such as bronchoaspiration. Reported use correlated well with objective use (r = 0.82). Most subjects reported an improvement in their respiratory health (64%) and were satisfied with the device (78%). Higher reported and objective use were associated with increased symptoms (p = 0.001) and higher satisfaction with the device (p = 0.008). We found no association between frequency of use and baseline cough peak flow (CPF), bulbar impairment, non-invasive ventilation use, living environment, or supervised administration. CONCLUSION: Regular home MI-E use was associated with greater symptom burden and overall satisfaction with the device and was not influenced by baseline CPF. Patients without substantial bronchorrhea might not use the MI-E regularly but might still need to use the device at home during acute events. Therefore, familiarity with the MI-E via appropriate and repeated practical training is crucial.

[Phage therapy for respiratory infections]. / Phagothérapie pour traiter les infections respiratoires.

The crisis of antibiotic resistance represents a global public health challenge, affecting particularly patients with respiratory infections. The use of (bacterio)phages for the treatment of bacterial infections (phage therapy) seems safe but its effectiveness has not yet been proven by controlled clinical trials. Nevertheless, phage therapy is regaining interest, encouraged by published cases treated successfully with personalized phage combinations as well as significant advances at a preclinical level. Standardized approaches in phage production and treatment administration, as well as future translational studies, are needed to improve our understanding and explore the potential of phage therapy.

La crise de l'antibiorésistance représente un enjeu considérable en santé publique, touchant particulièrement les patients avec des infections respiratoires. L'utilisation des (bactério)phages pour le traitement des infections bactériennes semble sécuritaire mais son efficacité n'a pas encore été formellement démontrée dans des essais cliniques contrôlés. La phagothérapie regagne de l'intérêt comme traitement personnalisé pour les patients qui ne répondent pas aux traitements standards, comme en témoignent les multiples cas publiés ainsi que des découvertes significatives au niveau préclinique. Des approches standardisées concernant la production et l'administration des phages ainsi que des études translationnelles sont nécessaires afin d'améliorer notre compréhension et d'explorer le potentiel de la phagothérapie.

Long-term outcome, clinical course and treatment approaches of paediatric langerhans cell histiocytosis: A greek reference centre report.

AIM: Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia with diverse clinical behaviour. In this article, we studied the clinical course, management and long-term outcomes of a paediatric cohort treated by our reference centre. METHODS: We retrospectively studied 66 children with LCH, consecutively diagnosed by a Greek reference centre from 1974 to 2020. RESULTS: The patients had a median age of 3.9 (range 0.0-15.9) years, 39 and 6 patients were diagnosed with unifocal or multifocal single system disease and 14 and 7 had multisystem disease with or without risk organ involvement. No late occurrence of clinical neurodegenerative disease or diabetes insipidus were observed at a median follow-up period of 4.1 (range 0.5-27.7) years. The 10-year event-free survival and overall survival were 65.0% and 90.3% and improved significantly over a 45-year period. Survival was superior in single system than multisystem cases. BRAF V600E mutation was found in 8/14 tested patients. Reactivation occurred in 12/66 patients (18.2%); 11 achieved remission and one patient died after a second relapse. CONCLUSION: LCH survival rates significantly increased in our cohort over time. Reactivation occurred in 18.2% patients, but no late neurodegeneration was found. The prognostic value of single system disease status vs. multisystem LCH was confirmed.

[Covid-19 respiratory sequelae : Screening and management]. / Séquelles respiratoires liées au Covid-19 : dépistage et prise en charge.

Infection with SARS-CoV-2 can affect multiple organ systems with variable severity and is known to frequently have a major impact on the respiratory system. Symptoms may persist for several months after infection, and are associated with a reduction of lung function, diminished exercise capacity and anomalies on chest CT. Guidelines on the post-acute care of patients with SARS-CoV-2 are now available. Pulmonary rehabilitation plays a central role in the recovery of exercise capacity, notably in severe cases. The role of specific therapies, such as corticosteroids, anti-fibrotics and lung transplantation remains uncertain and needs to be evaluated on a case-by-case basis.

L'infection à SARS-CoV-2 conduit à une atteinte multisystémique de gravité variable, fréquemment avec un impact majeur sur le système respiratoire. Les symptômes peuvent persister plusieurs mois après l'infection initiale. Ils sont parfois associés à une diminution des fonctions pulmonaires et de la capacité à l'effort, ainsi qu'à des anomalies au CT-scan thoracique. Il existe actuellement des recommandations de suivi et de prise en charge des patients atteints par le Covid-19 pour la phase postaiguë. La réhabilitation pulmonaire joue un rôle central dans la récupération de la capacité d'effort, surtout dans les formes sévères. La place des traitements spécifiques des atteintes pulmonaires, notamment les corticostéroïdes, les antifibrotiques et la transplantation, reste encore incertaine et doit être considérée au cas par cas.

Immunotherapy-Induced Airway Disease: A New Pattern of Lung Toxicity of Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICIs) have been shown to improve overall and progression-free survival in various cancers but have been associated with various immune-related adverse events (IRAEs), including interstitial lung disease, especially organizing pneumonia. We report 2 cases of isolated severe airway disease attributable to ICIs, a rarely reported pattern of lung toxicity. The first patient received nivolumab with or without ipilimumab in a randomized double-blind trial for locoregional metastatic melanoma. The second patient was treated with nivolumab for lung adenocarcinoma. An IRAE was suspected in both cases due to a temporal relationship between ICI initiation and symptom onset. ICIs were stopped, and high-dose prednisone, inhaled corticosteroids, and bronchodilators were administered, allowing a rapid clinical and functional improvement in Patient 1. In Patient 2, despite prolonged high-dose prednisone, only a stabilization of forced expiratory volume in 1 s could be achieved, and the disease course was complicated by respiratory infections resulting in further loss of lung function. The patient died 1 year later due to progression of metastatic disease. These 2 cases suggest that pulmonary IRAEs secondary to ICIs may present as isolated bronchitis or bronchiolitis, with variable outcomes following ICI withdrawal and systemic corticosteroids.

Expression of phosphatase and tensin homologue in imprint smears of endometrial carcinoma.

OBJECTIVE: The aims of this study were to determine the expression of phosphatase and tensin homologue (PTEN) in endometrial adenocarcinomas (as a potential prognostic indicator before treatment) in imprint smears and to correlate the results with clinicopathological parameters of primary untreated endometrial cancer patients. METHODS: A total of 126 patients with endometrial carcinoma were evaluated with samples freshly resected after a total abdominal hysterectomy during a 29-month period. The expression of PTEN was assessed by immunocytochemistry. RESULTS: In total, 102 cases were type I and 24 type II endometrial adenocarcinomas. High expression of PTEN was more frequent in type I (42/102) compared to type II (6/24) adenocarcinomas, to less advanced and aggressive clinical stage (stage I: 41/79, stage II: 5/13, stage III: 2/19, stage IV: 1/15) as well as in low grade (grade 1: 26/42, grade 2: 20/57) compared to high-grade (grade 3: 8/27) carcinomas. The nonaffected lymph nodes showed high expression of PTEN (in 43.3%) than the affected lymph nodes (in 5.9%). Also, in 45 out of 74 cases with myometrial invasion <50%, there was positive expression of PTEN in contrast to 12 out of 52 cases with depth of myometrial invasion >50%. CONCLUSIONS: Immunocytochemical findings from PTEN stain, in addition to cytomorphological features, appeared to be a useful marker in the diagnosis and in the postoperative prognosis of endometrial carcinoma in endometrial cytology with imprint smears and that high PTEN expression is related to morphological features of less aggressiveness tumours.

[Noninvasive ventilation for chronic hypercapnic respiratory failure]. / Rôle de la ventilation non invasive dans l'insuffisance respiratoire hypercapnique chronique.

Chronic hypercapnic respiratory failure is essentially a ventilatory failure. Noninvasive ventilation (NIV ) reduces the work of breathing, improves pulmonary compliance and alveolar ventilation, corrects gas exchange disorders and improves dyspnoea. However, treatment efficacy depends on the underlying pathology, on correct timing and on patient compliance. In this context, the principal role of the primary care physician is to search for, at every visit of at risk patients, signs and symptoms of ventilatory failure and to refer the patient to a respiratory care specialist. He also plays a role in the follow up of patients under noninvasive ventilation for the detection of clinical parameters suggesting NIV failure.

L'insuffisance respiratoire hypercapnique chronique est essentiellement une défaillance ventilatoire. La ventilation non invasive (VNI) diminue le travail des muscles respiratoires, augmente la compliance thoracique, améliorant ainsi la dyspnée et les troubles des échanges gazeux. Toutefois, l'efficacité du traitement dépend de la pathologie sous-jacente, du bon timing d'initiation et de la compliance du patient. Dans ce contexte, le rôle principal du médecin de premier recours consiste à rechercher, lors de chaque visite médicale de patients à risque, des signes et symptômes de défaillance ventilatoire qui nécessitent de référer le patient à un pneumologue. Son rôle est aussi important dans le suivi des patients ventilés pour la détection précoce des paramètres cliniques suggérant un échec de VNI.

Allergic bronchopulmonary aspergillosis as an initial manifestation of cystic fibrosis: Diagnostic and therapeutic implications in the era of CFTR modulators.

Allergic bronchopulmonary aspergillosis (ABPA) results from complex hypersensitivity reactions to Aspergillus fumigatus, which often occur in patients with asthma, cystic fibrosis (CF), or CF transmembrane conductance regulator (CFTR)-related disorders. Genetic predisposition, particularly variants of the CFTR gene, probably plays a significant role in the development of ABPA. We present the case of a 20-year-old male with ABPA and bronchiectasis that was initially misdiagnosed as a result of normal sweat chloride values and negative first-level genetic testing results. Comprehensive CFTR gene sequencing revealed 2 pathogenic variants, R347H and D1152H, which together with the clinical phenotype and functional tests, supported the diagnosis of CF. Treatment with elexacaftor/tezacaftor/ivacaftor resulted in significant clinical and functional improvement, including a marked decrease in total IgE levels, suggesting a potential role for CFTR modulators in controlling ABPA. This case illustrates the evolving understanding of CF as a spectrum of disorders in which CFTR dysfunction may manifest subtly and variably, necessitating a high index of suspicion and a comprehensive diagnostic approach to ensure timely treatment in the era of highly effective CFTR modulators.

Giant Juvenile Fibroadenoma: Case Report and Review of the Literature.

Fibroadenomas are common benign breast tumors. Fibroadenomas that exceed 5 cm in diameter, weigh more than 500 g, or replace more than four-fifths of the breast are characterized as giant. A fibroadenoma diagnosed in patients during childhood or adolescence is characterized as juvenile. An extensive PubMed search of the literature in English up until August 2022 was performed. In addition, a rare case of a gigantic fibroadenoma in an 11-year-old premenarchal girl who was referred to our adolescent gynecology center is presented here. Eighty-seven cases of giant juvenile fibroadenomas have been reported in the literature along with our case. Patients with giant juvenile fibroadenoma presented at a mean age of 13.92 years and usually after menarche. Juvenile fibroadenomas are usually unilateral, occurring either in the right or the left breast; the majority of them are diagnosed when they are already more than 10 cm in size, and they are most frequently treated with total lump excision. Differential diagnosis includes phyllodes tumors and pseudo-angiomatous stromal hyperplasia. Conservative management is feasible, but surgical excision is recommended to patients with suspicious imaging features or when the mass grows rapidly.

Successful pregnancy in a cystic fibrosis patient with a severe impairment of lung function receiving Elexacaftor-Tezacaftor-Ivacaftor.

Before the arrival of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulators women with CF and impaired lung function were experiencing a high risk of complications and mortality during and the years after pregnancy. The arrival of the highly efficient CFTR modulator, Elexacaftor-Tezacaftor-Ivacaftor (ETI) resulted in an improvement of lung function, quality of life and fertility. Here we report a case of successful pregnancy and uncomplicated delivery for a CF patient with severely impaired lung function receiving ETI prior to conception.

Phage therapy for pulmonary infections: lessons from clinical experiences and key considerations.

Lower respiratory tract infections lead to significant morbidity and mortality. They are increasingly caused by multidrug-resistant pathogens, notably in individuals with cystic fibrosis, hospital-acquired pneumonia and lung transplantation. The use of bacteriophages (phages) to treat bacterial infections is gaining growing attention, with numerous published cases of compassionate treatment over the last few years. Although the use of phages appears safe, the lack of standardisation, the significant heterogeneity of published studies and the paucity of robust efficacy data, alongside regulatory hurdles arising from the existing pharmaceutical legislation, are just some of the challenges phage therapy has to overcome. In this review, we discuss the lessons learned from recent clinical experiences of phage therapy for the treatment of pulmonary infections. We review the key aspects, opportunities and challenges of phage therapy regarding formulations and administration routes, interactions with antibiotics and the immune system, and phage resistance. Building upon the current knowledge base, future pre-clinical studies using emerging technologies and carefully designed clinical trials are expected to enhance our understanding and explore the therapeutic potential of phage therapy.

Expression of cyclooxygenase-2 in imprint smears of endometrial carcinoma.

BACKGROUND: Worldwide, endometrial carcinoma is one of the most frequently diagnosed cancers among women and a considerable cause of death. The aims of this study were to determine the expression of cyclooxygenase-2 (COX-2) in endometrial adenocarcinoma in imprint smears as an alternative technique and to correlate the results with clinicopathologic parameters of primary untreated endometrial cancer patients. METHODS: One hundred twenty-six patients with endometrial carcinoma were evaluated with samples freshly resected after a total abdominal hysterectomy during a 29-month period. The cytologic imprint smears were obtained by touching the cut surface of cancer tissues and the expression of COX-2 was assessed by immunocytochemistry. RESULTS: The positive expression of COX-2 in malignant cells, was accompanied by morphologic features of more aggressiveness (pathogenetic type II, advanced clinical stage, mainly high grade, deep myometrial involvement >1/2) tumors and the affected from the disease lymph nodes cases showed higher positivity (41.2%) than the non-affected (13.4%). CONCLUSION: Immunocytochemical findings from COX-2 stain in cancer cells could be a predictor of prognosis in most cases in endometrial cytology with imprint smears. Furthermore, positive expression of COX-2 in cancer cells was related to morphologic features of more aggressiveness tumors.

Malignant pleural effusion from papillary thyroid carcinoma diagnosed by pleural effusion cytology: A case report.

Papillary thyroid carcinoma (PTC) is by far the most common thyroid malignancy (over 85%) of all the thyroid cancers. It has excellent prognosis and 10-year survival rate in most of the cases (95%). Most of the tumors are indolent and do not recur or metastasize after removal. However, widespread metastases to lung, skeleton, central nervous system and, occasionally, other organs may be observed. In rare instances, this disease may metastasize to the pleura and manifest as a malignant pleural effusion (MPE) and portend poor prognosis. This article reports the cytomorphologic and immunocytochemical findings of a female patient with a symptomatic pleural effusion resulting from PTC metastatic to the pleura. Pleural fluid cytology revealed abundant papillary clusters with relatively nuclear pleomorphism, intranuclear cytoplasmic inclusions and nuclear grooves, small and distinct nucleoli as well as small discrete vacuoles. Psammoma bodies were not seen. Immunocytochemical staining was positive for TGB, EMA, Ber-EP4, CK19, and negative for TTF-1. Metastasis of PTC to pleural fluid is extremely rare and diagnosing the disease by cytology is challenging and requires medical expertise as well as knowledge of clinical context and immunocytochemical staining. Additionally, a cytologic diagnosis of MPE due to PTC provides important treatment information and plays an important role in prognosis.

Solitary Plasmacytoma of the Mesentery: A Systematic Clinician's Diagnosis.

INTRODUCTION: Plasmacytoma is an uncommon plasma cell neoplasm and its localized form is solitary plasmacytoma of the bone and solitary extramedullary plasmacytoma. Solitary plasmacytoma of the mesentery is extremely rare, reported only in a handful of cases. CASE PRESENTATION: A 47-year-old man with nonspecific abdominal complains was found to have an ill-defined mass on his mesenteric root. Laparoscopic biopsy and stepwise histopathological examination revealed a mesenteric plasmacytoma, and extensive imaging and laboratory investigations led to the diagnosis of the solitary mesenteric plasmacytoma. The patient underwent definitive radiotherapy and remains under remission one year later. DISCUSSION: Plasma cell dyscrasias include a variant of proliferative disease, characterized by clonal expansion of bone marrow plasma cells, producing a massive quantity of monoclonal immunoglobulin called paraprotein or M-protein. Solitary extramedullary plasmacytoma accounts for only 3-5% of all plasma cell neoplasms. Meticulous adherence to the established diagnostic criteria helps the clinician to set the correct, yet very unusual and unexpected diagnosis.

Electrical synapses: a dynamic signaling system that shapes the activity of neuronal networks.

Gap junctions consist of intercellular channels dedicated to providing a direct pathway for ionic and biochemical communication between contacting cells. After an initial burst of publications describing electrical coupling in the brain, gap junctions progressively became less fashionable among neurobiologists, as the consensus was that this form of synaptic transmission would play a minimal role in shaping neuronal activity in higher vertebrates. Several new findings over the last decade (e.g. the implication of connexins in genetic diseases of the nervous system, in processing sensory information and in synchronizing the activity of neuronal networks) have brought gap junctions back into the spotlight. The appearance of gap junctional coupling in the nervous system is developmentally regulated, restricted to distinct cell types and persists after the establishment of chemical synapses, thus suggesting that this form of cell-cell signaling may be functionally interrelated with, rather than alternative to chemical transmission. This review focuses on gap junctions between neurons and summarizes the available data, derived from molecular, biological, electrophysiological, and genetic approaches, that are contributing to a new appreciation of their role in brain function.

Simultaneous drug-eluting and bare-metal stent implantation: long-term clinical outcome and findings of clinically indicated coronary angiography.

BACKGROUND: Simultaneous drug-eluting stent (DES) and bare-metal stent (BMS) implantation is occasionally employed in clinical practice, but its long-term clinical and angiographic outcome is not clear. HYPOTHESIS: We aimed to describe the long-term clinical outcome and the findings of clinically indicated coronary angiography in patients subjected to simultaneous DES and BMS implantation ("hybrid stenting"). METHODS: We identified 236 patients (mean age 62.9 ± 11.4 years, 76.7% men) who had undergone percutaneous coronary intervention with at least 1 DES and 1 BMS. At a median follow-up of 42 months (range, 6-89 months) available in 222 patients, 13 (5.9%) patients died from cardiac causes, 13 (5.9%) experienced nonfatal acute myocardial infarction, and 24 (10.8%) experienced unstable angina. Clinically indicated repeat coronary angiography was performed in 64 patients (28.8%). RESULTS: Thirty-one patients (14%) had target lesion revascularization (TLR). The DES demonstrated lower TLR rates (15.9% vs 36.9%, P = 0.002) and lower late loss (0.44 ± 0.5 mm vs 0.68 ± 0.7 mm, P = 0.009) compared with BMS. Use of DES was independently associated with lower risk for binary restenosis (hazard ratio [HR]: 0.41, 95% confidence interval [CI]: 0.19-0.89, P = 0.03) and TLR (HR: 0.26, 95% CI: 0.12-0.54, P<0.001). CONCLUSIONS: Although a hybrid stenting strategy demonstrates a reasonable long-term prognosis even in high-risk patients, DES have a better angiographic outcome compared with BMS under the influence of common patient-related restenosis risk factors.