Lymphangioleiomyomatosis, multifocal micronodular pneumocyte hyperplasia, and sarcoidosis : More pathological findings in the same chest CT, or a single pathological pathway?

Background: Autoimmune hepatitis/primary biliary cirrhosis overlap syndrome, lymphangioleiomyomatosis/tuberous sclerosis complex (LAM-TSC), and sarcoidosis are three rare diseases. Here we present, to the best of our knowledge, the first description of a patient with the coexistence of these three diseases. Case presentation: A 47-year-old woman affected by LAM-TSC and primary biliary cirrosis/autoimmune hepatitis overlap syndrome. During her follow up a high resolution chest CT scan (HRTC) confirmed the presence of both multiple cysts and micronodular opacities consistent with multifocal micronodular pneumocytes hyperlasia (MMPH), and revealed multiple hilar-mediastinal symmetrical lymphadenopathies suggestive of sarcoidosis. Simultaneously, subcutaneous nodules appeared on her forearm bilaterally. Cutaneous biopsy showed granulomatous dermatitis with sarcoid-like granulomas. A diagnosis of stage I pulmonary sarcoidosis was made. No treatment for sarcoidosis was initiated since the patient had neither systemic involvement, nor respiratory impairment. Conclusions: The presence of more than one rare disease should challenge the concept of a potential common underlying mechanism, since the a priori probability of the concomitant presence of different conditions with different pathogenic mechanisms - especially if rare diseases - is low. We speculate that the dysregulation of the pathway involving mTOR and MAPK and their interaction might play a role in the pathogenesis of other diseases, including sarcoidosis

Efficacy of Benralizumab in severe asthma in real life and focus on nasal polyposis

Introduction: Severe asthma occurs in 5–10% of asthmatic patients, with nasal polyposis as one of the most frequent comorbidity. Benralizumab was recently marketed, thus we could analyse its effects in real-life in severe asthma, and compare the effects of the drug in patients with and without polyposis. Methods: Patients with severe asthma, receiving Benralizumab were enrolled in Italian asthma centres. The efficacy criteria for asthma (exacerbation rate, oral corticosteroid intake, hospitalizations, pulmonary function, exhaled nitric oxide) were evaluated at baseline and after 24 weeks of treatment. Patients were then sub-analysed according to the presence/absence of nasal polyposis. Results: Fifty-nine patients with severe uncontrolled asthma (21 males, age range 32–78) and treated with benralizumab for at least 24 weeks has been evaluated, showing significant improvements in asthma-related outcomes, except for pulmonary function and exhaled nitric oxide. This included a reduction in the sino-nasal outcome-22 score versus baseline of 13.7 points (p = .0037) in the 34 patients with nasal polyposis. Anosmia disappeared in 31% patients (p = .0034). When comparing the groups with and without nasal polyposis, a similar reduction of exacerbations was seen, with a greater reduction of the steroid dependence in patients with polyposis (−72% vs −53%; p < .0001), whereas lung function was significantly more improved (12% vs 34%, p = .0064) without polyposis patients. Conclusions: Benralizumab, after 6 months of treatment, confirmed its efficacy in severe asthma, and also in nasal polyposis, which is the most frequent comorbidity. The efficacy of Benralizumab in reducing steroid dependence was even higher in patients with polyposis

Women with TSC : Relationship between Clinical, Lung Function and Radiological Features in a Genotyped Population Investigated for Lymphangioleiomyomatosis

The advent of pharmacological therapies for lymphangioleiomyomatosis (LAM) has made early diagnosis important in women with tuberous sclerosis complex (TSC), although the lifelong cumulative radiation exposure caused by chest computer tomography (CT) should not be underestimated. We retrospectively investigated, in a cohort of TSC outpatients of San Paolo Hospital (Milan, Italy) 1) the role of pulmonary function tests (PFTs) for LAM diagnosis, 2) the association between LAM and other features of TSC (e.g. demography, extrapulmonary manifestations, genetic mutations, etc.), and 3) the characteristics of patients with multifocal micronodular pneumocyte hyperplasia (MMPH). Eighty-six women underwent chest CT scan; pulmonary involvement was found in 66 patients (77%; 49% LAM with or without MMPH, and 28% MMPH alone). LAM patients were older, with a higher rate of pneumothorax, presented more frequently with renal and hepatic angiomyolipomas, and tended to have a TSC2 mutation profile. PFTs, assessed in 64% of women unaffected by cognitive impairments, revealed a lower lung diffusion capacity in LAM patients. In multivariate analysis, age, but not PFTs, resulted independently associated with LAM diagnosis. Patients with MMPH alone did not show specific clinical, functional or genetic features. A mild respiratory impairment was most common in LAM-TSC patients: In conclusions, PFTs, even if indicated to assess impairment in lung function, are feasible in a limited number of patients, and are not significantly useful for LAM diagnosis in women with TSC

Continuous population-level monitoring of SARS-CoV-2 seroprevalence in a large European metropolitan region.

Effective public health measures against SARS-CoV-2 require granular knowledge of population-level immune responses. We developed a Tripartite Automated Blood Immunoassay (TRABI) to assess the IgG response against three SARS-CoV-2 proteins. We used TRABI for continuous seromonitoring of hospital patients and blood donors (n = 72'250) in the canton of Zurich from December 2019 to December 2020 (pre-vaccine period). We found that antibodies waned with a half-life of 75 days, whereas the cumulative incidence rose from 2.3% in June 2020 to 12.2% in mid-December 2020. A follow-up health survey indicated that about 10% of patients infected with wildtype SARS-CoV-2 sustained some symptoms at least twelve months post COVID-19. Crucially, we found no evidence of a difference in long-term complications between those whose infection was symptomatic and those with asymptomatic acute infection. The cohort of asymptomatic SARS-CoV-2-infected subjects represents a resource for the study of chronic and possibly unexpected sequelae

Mobilise-D insights to estimate real-world walking speed in multiple conditions with a wearable device

This study aimed to validate a wearable device’s walking speed estimation pipeline, considering complexity, speed, and walking bout duration. The goal was to provide recommendations on the use of wearable devices for real-world mobility analysis. Participants with Parkinson’s Disease, Multiple Sclerosis, Proximal Femoral Fracture, Chronic Obstructive Pulmonary Disease, Congestive Heart Failure, and healthy older adults (n = 97) were monitored in the laboratory and the real-world (2.5 h), using a lower back wearable device. Two walking speed estimation pipelines were validated across 4408/1298 (2.5 h/laboratory) detected walking bouts, compared to 4620/1365 bouts detected by a multi-sensor reference system. In the laboratory, the mean absolute error (MAE) and mean relative error (MRE) for walking speed estimation ranged from 0.06 to 0.12 m/s and − 2.1 to 14.4%, with ICCs (Intraclass correlation coefficients) between good (0.79) and excellent (0.91). Real-world MAE ranged from 0.09 to 0.13, MARE from 1.3 to 22.7%, with ICCs indicating moderate (0.57) to good (0.88) agreement. Lower errors were observed for cohorts without major gait impairments, less complex tasks, and longer walking bouts. The analytical pipelines demonstrated moderate to good accuracy in estimating walking speed. Accuracy depended on confounding factors, emphasizing the need for robust technical validation before clinical application. Trial registration: ISRCTN – 12246987

The reciprocal link between sleep and immune responses

Good sleep is necessary for both physical and mental health; sleep and immune responses are reciprocally and closely linked. Sleep loss impairs the immune response, while, on the other hand, the immune response, activated for instance by an infection, alters sleep. Sleep alterations induced by immune activation are mediated by cytokines such as interleukin-1. In the past, it was thought that cytokines were produced only by the immune system, and active only there as signaling molecules. Today it is clear that IL-1 and other cytokines are present and active in the healthy brain, where they physiologically interact with the brain circuits and the neurotransmitter systems (for instance the serotonergic, GABAergic, and cholinergic systems) that control sleep. These interactions are altered by immune response, and, as a result, non-rapid eye move- ment (NREM) sleep is increased and fragmented, whereas rapid eye movements (REM) sleep is inhibited

Effects of the new, non benzodiazepine, anxiolytic drug buspirone on the serotonergic system

The effects of the new, non benzodiazepine, anxiolytic drug buspirone and its metabolite 1-(2-pyrimidinyl)-piperazine (1-PP) were studied on the serotonergic system by in vivo voltammetry. This technique, in association with carbon fiber microelectrodes, chronically implanted in the hippocampus, caudate nucleus and nucleus accumbens of freely moving rats, continuously recorded 5-hydroxy-indoleacetic acid (5HIAA), the serotonin metabolite, in the extracellular space. The administration of buspirone (10 mg/kg i.p.) induced a decrease in 5HIAA in the hippocampus but not in the caudate nucleus and nucleus accumbens. This effect lasted about 150 min; 1-PP was found to be ineffective. The regional specificity of buspirone suggests a role for hippocampal serotonin in anxiety

EFFECT OF BUSPIRONE AND ITS METABOLITE 1-(2-PYRIMYDINYL)-PIPERAZINE ON HIPPOCAMPAL SEROTONINERGIC SYSTEM, STUDIED IN FREELY MOVING RATS

The effects of the anxiolytic drug buspirone and its metabolite 1-(2-pyrimidinyl)-piperazine (1PP) were studied on the serotoninergic system in the hippocampus of freely moving rats. Pulse voltammetry was used in association with chronically implanted carbon fiber microelectrodes to record 5HIAA, the serotonin metabolite in the extracellular space, almost continuously. Buspirone, 2.5 mg/kg i.p. was ineffective, but the dose of 10 mg/kg lowered 5HIAA between about 45 and 150 min; the same decrease was obtained with 40 mg/kg. This effect can be explained by an agonistic action on 5HT1 A receptors. The metabolite 1PP, which displays \u3b12 adrenoceptor blocking properties, either had no effect or raised extracellular 5HIAA, depending on the dose (1.5 or 6 mg/kg). The rapid metabolization of buspirone to 1PP can thus explain the short time course of the drug effect. Pretreatment with 1PP could only partially prevent buspirone's effect on the serotoninergic system