Non-tuberculous mycobacterial diseases in children

Non-tuberculous mycobacteria (NTMs) are ubiquitous and opportunistic emerging bacteria with the potential to colonize and eventually infect either immunocompromised or immunocompetent individuals. In the last three decades, the prevalence of disease caused by NTMs has increased in several countries. The increased prevalence of NTM infection can be explained by an ageing population with rising comorbidities, HIV infection, the common use of immunosuppressive drugs, and improved diagnostic methods. The aim of this review is to demonstrate the clinical relevance of NTMs in children, describing their features and manifestations, diagnostic tools, and therapeutic approaches. We collected data from the literature about NTM infections in young patients over the past five years (2014–2019) using the keywords “non-tuberculous”, “mycobacteria”, “paediatric”, “NTM”, “cystic fibrosis”, and “children”. Recent literature points out that NTMs are ubiquitous, with several species including both those that are pathogens for humans and those that are not. This means that, if a mycobacterium is isolated from a patient’s specimen, we have to distinguish between a simple colonization and an NTM-related disease. The start of treatment depends on many factors that are necessary to consider, such as clinical and imaging features, patient comorbidity and immunocompetence, drug adverse effects, and compliance with a very long therapy that can last many months. Due to the increasing prevalence and clinical relevance of NTMs, guidelines for their optimal management, especially in the presence of chronic underlying disease, are urgently needed

An Atypical Presentation of Primary Hyperparathyroidism in an Adolescent: A Case Report of Hypercalcaemia and Neuropsychiatric Symptoms Due to a Mediastinal Parathyroid Adenoma

Psychiatric disorders are rare clinical manifestations of hypercalcaemia in the pediatric population, are relatively more frequent during adolescence and are often overlooked in cases of severe hypercalcaemia. We described the case of a 17-year-old girl affected by anorexia nervosa, depression and self-harm with incidental detection of moderate hypercalcaemia. Clinical, laboratory and instrumental tests demonstrated that hypercalcaemia was secondary to primary hyperparathyroidism (PHPT) due to a mediastinal parathyroid adenoma in the thymic parenchyma. After parathyroidectomy with robot-assisted surgery, we observed the restoration of calcium and PTH levels in addition to an improvement in psychiatric symptoms. This case demonstrates that serum calcium concentration should be evaluated in adolescents with neurobehavioural symptoms and in cases of hypercalcaemia PHPT should be excluded. Surgery represents the cornerstone of the management of PHPT and may contribute to improving quality of life and psychological function in these patients. However, the complexity of neurological involvement in cases of hypercalcaemia due to PHPT requires further investigations to establish the real impact of this condition on the neurocognitive sphere

An unusual dysphagia for solids in a 17-year-old girl due to a lusoria artery: A case report and review of the literature

Background: Dysphagia is a condition that can have many underlying causes, often different between adults and children and its early diagnosis is crucial especially during childhood and adolescence, given the importance of proper nutritional intake to ensure adequate growth and development. Case report: We described the case of a 17-year-old girl reporting dysphagia for solids for approximately one month. No symptoms were previously referred. Oesophagogastroduodenoscopy was performed, detecting an image of ab extrinseco compression at the level of the mid-cervical oesophagus. An upper gastrointestinal tract radiography confirmed an oesophageal impression above the arch of the aorta suggestive of vascular abnormality. Computed tomography angiography and three-dimensional reconstruction techniques showed the presence of a lusoria artery that originated from the medial margin of the descending aorta and crossed the trachea and oesophagus posteriorly to the distal third. The lusoria artery was transected via a left thoracotomy and re-implanted into the right common carotid artery with complete symptom resolution. Conclusions: Dysphagia lusoria is an impairment of swallowing due to compression from an aberrant right subclavian artery. The diagnosis is always difficult, as the symptoms are often nonspecific. It is imperative to accurately identify and properly manage dysphagia in pediatric age and this is only possible with an anamnestic, clinical and instrumental process that takes into account an adequate differential diagnosis

Coronavirus infections in children: From SARS and MERS to COVID-19, a narrative review of epidemiological and clinical features

Emerging and re-emerging viruses represent an important challenge for global public health. In the 1960s, coronaviruses (CoVs) were recognized as disease agents in humans. In only two decades, three strains of CoVs have crossed species barriers rapidly emerging as human pathogens resulting in life-threaten-ing disease with a pandemic potential: severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002, Middle-East respiratory syndrome coronavirus (MERS-CoV) in 2012 and the recently emerged SARS-CoV-2. This narrative review aims to provide a comprehensive overview of epidemiological, pathogenic and clinical features, along with diagnosis and treatment, of the ongoing epidemic of new coronavirus disease 2019 (COVID-19) in the pediatric population in comparison to the first two previous deadly coronavirus outbreaks, SARS and MERS. Literature analysis showed that SARS-CoV, MERS-CoV and SARS-CoV-2 infections seem to affect children less commonly and less severely as compared with adults. Since children are usually asymptomatic, they are often not tested, leading to an underestimate of the true numbers infected. Most of the documented infections belong to family clusters, so the importance of children in transmitting the virus remains uncertain. Like in SARS and MERS infection, there is the possibility that children are not an important reservoir for novel CoVs and this may have important implications for school attendance. While waiting for an effective against SARS-CoV-2, further prevalence studies in paediatric age are needed, in order to clarify the role of children in different age groups in the spread of the infection. (www.actabiomedica.it)

Brain hemodynamic intermediate phenotype links Vitamin B12 to cognitive profile of healthy and mild cognitive impaired subjects

Vitamin B12, folate, and homocysteine are implicated in pivotal neurodegenerative mechanisms and partake in elders' mental decline. Findings on the association between vitamin-related biochemistry and cognitive abilities suggest that the structural and functional properties of the brain may represent an intermediate biomarker linking vitamin concentrations to cognition. Despite this, no previous study directly investigated whether vitamin B12, folate, and homocysteine levels are sufficient to explain individual neuropsychological profiles or, alternatively, whether the activity of brain regions modulated by these compounds better predicts cognition in elders. Here, we measured the relationship between vitamin blood concentrations, scores at seventeen neuropsychological tests, and brain activity of sixty-five elders spanning from normal to Mild Cognitive Impairment. We then evaluated whether task-related brain responses represent an intermediate phenotype, providing a better prediction of subjects' neuropsychological scores, as compared to the one obtained considering blood biochemistry only. We found that the hemodynamic activity of the right dorsal anterior cingulate cortex was positively associated (p value < 0 05 cluster corrected) with vitamin B12 concentrations, suggesting that elders with higher B12 levels had a more pronounced recruitment of this salience network region. Crucially, the activity of this area significantly predicted subjects' visual search and attention abilities (p value = 0 0023), whereas B12 levels per se failed to do so. Our results demonstrate that the relationship between blood biochemistry and elders' cognitive abilities is revealed when brain activity is included into the equation, thus highlighting the role of brain imaging as intermediate phenotype.Vitamin B12, folate, and homocysteine are implicated in pivotal neurodegenerative mechanisms and partake in elders' mental decline. Findings on the association between vitamin-related biochemistry and cognitive abilities suggest that the structural and functional properties of the brain may represent an intermediate biomarker linking vitamin concentrations to cognition. Despite this, no previous study directly investigated whether vitamin B12, folate, and homocysteine levels are sufficient to explain individual neuropsychological profiles or, alternatively, whether the activity of brain regions modulated by these compounds better predicts cognition in elders. Here, we measured the relationship between vitamin blood concentrations, scores at seventeen neuropsychological tests, and brain activity of sixty-five elders spanning from normal to Mild Cognitive Impairment. We then evaluated whether task-related brain responses represent an intermediate phenotype, providing a better prediction of subjects' neuropsychological scores, as compared to the one obtained considering blood biochemistry only. We found that the hemodynamic activity of the right dorsal anterior cingulate cortex was positively associated (p value < 0 05 cluster corrected) with vitamin B12 concentrations, suggesting that elders with higher B12 levels had a more pronounced recruitment of this salience network region. Crucially, the activity of this area significantly predicted subjects' visual search and attention abilities (p value = 0 0023), whereas B12 levels per se failed to do so. Our results demonstrate that the relationship between blood biochemistry and elders' cognitive abilities is revealed when brain activity is included into the equation, thus highlighting the role of brain imaging as intermediate phenotype

Randomized trial on the effects of a combined physical/cognitive training in aged MCI subjects: the Train the Brain study

Age-related cognitive impairment and dementia are an increasing societal burden. Epidemiological studies indicate that lifestyle factors, e.g. physical, cognitive and social activities, correlate with reduced dementia risk; moreover, positive effects on cognition of physical/cognitive training have been found in cognitively unimpaired elders. Less is known about effectiveness and action mechanisms of physical/cognitive training in elders already suffering from Mild Cognitive Impairment (MCI), a population at high risk for dementia. We assessed in 113 MCI subjects aged 65-89 years, the efficacy of combined physical-cognitive training on cognitive decline, Gray Matter (GM) volume loss and Cerebral Blood Flow (CBF) in hippocampus and parahippocampal areas, and on brain-blood-oxygenation-level-dependent (BOLD) activity elicited by a cognitive task, measured by ADAS-Cog scale, Magnetic Resonance Imaging (MRI), Arterial Spin Labeling (ASL) and fMRI, respectively, before and after 7 months of training vs. usual life. Cognitive status significantly decreased in MCI-no training and significantly increased in MCI-training subjects; training increased parahippocampal CBF, but no effect on GM volume loss was evident; BOLD activity increase, indicative of neural efficiency decline, was found only in MCI-no training subjects. These results show that a non pharmacological, multicomponent intervention improves cognitive status and indicators of brain health in MCI subjects

CIS controls the functional polarization of GM-CSF-derived macrophages

The cytokine granulocyte-macrophage-colony stimulating factor (GM-CSF) possesses the capacity to differentiate monocytes into macrophages (MØs) with opposing functions, namely, proinflammatory M1-like MØs and immunosuppressive M2-like MØs. Despite the importance of these opposing biological outcomes, the intrinsic mechanism that regulates the functional polarization of MØs under GM-CSF signaling remains elusive. Here, we showed that GM-CSF-induced MØ polarization resulted in the expression of cytokine-inducible SH2-containing protein (CIS) and that CIS deficiency skewed the differentiation of monocytes toward immunosuppressive M2-like MØs. CIS deficiency resulted in hyperactivation of the JAK-STAT5 signaling pathway, consequently promoting downregulation of the transcription factor Interferon Regulatory Factor 8 (IRF8). Loss- and gain-of-function approaches highlighted IRF8 as a critical regulator of the M1-like polarization program. In vivo, CIS deficiency induced the differentiation of M2-like macrophages, which promoted strong Th2 immune responses characterized by the development of severe experimental asthma. Collectively, our results reveal a CIS-modulated mechanism that clarifies the opposing actions of GM-CSF in MØ differentiation and uncovers the role of GM-CSF in controlling allergic inflammation.Shengbo Zhang ... Naiara G. Bediaga ... et al

Long-term beneficial impact of the randomised trial ‘Train the Brain’, a motor/cognitive intervention in mild cognitive impairment people: effects at the 14-month follow-up

No treatment options are currently available to counteract cognitive deficits and/or delay progression towards dementia in older people with mild cognitive impairment (MCI). The ‘Train the Brain’ programme is a combined motor and cognitive intervention previously shown to markedly improve cognitive functions in MCI individuals compared to non-trained MCI controls, as assessed at the end of the 7-month intervention. Here, we extended the previous analyses to include the long-term effects of the intervention and performed a data disaggregation by gender, education and age of the enrolled participants. We report that the beneficial impact on cognitive functions was preserved at the 14-month follow-up, with greater effects in low-educated compared to high-educated individuals, and in women than in men

Effects of combined training on neuropsychiatric symptoms and quality of life in patients with cognitive decline

Background and aims: Cognitive impairments associated with aging and dementia are major sources of neuropsychiatric symptoms (NPs) and deterioration in quality of life (QoL). Preventive measures to both reduce disease and improve QoL in those affected are increasingly targeting individuals with mild cognitive impairment (MCI) at early disease stage. However, NPs and QoL outcomes are too commonly overlooked in intervention trials. The purpose of this study was to test the effects of physical and cognitive training on NPs and QoL in MCI. Methods: Baseline data from an MCI court (N = 93, mean age 74.9 ± 4.7) enrolled in the Train the Brain (TtB) study were collected. Subjects were randomized in two groups: a group participated to a cognitive and physical training program, while the other sticked to usual standard care. Both groups underwent a follow-up re-evaluation after 7 months from baseline. NPs were assessed using the Neuropsychiatric Inventory (NPI) and QoL was assessed using Quality of Life-Alzheimer’s Disease (QOL-AD) scale. Results: After 7 months of training, training group exhibited a significant reduction of NPs and a significant increase in QOL-AD with respect to no-training group (p = 0.0155, p = 0.0013, respectively). Our preliminary results suggest that a combined training can reduce NPs and improve QoL. Conclusions: Measuring QoL outcomes is a potentially important factor in ensuring that a person with cognitive deficits can ‘live well’ with pathology. Future data from non-pharmacological interventions, with a larger sample and a longer follow-up period, could confirm the results and the possible implications for such prevention strategies for early cognitive decline.Background and aims: Cognitive impairments associated with aging and dementia are major sources of neuropsychiatric symptoms (NPs) and deterioration in quality of life (QoL). Preventive measures to both reduce disease and improve QoL in those affected are increasingly targeting individuals with mild cognitive impairment (MCI) at early disease stage. However, NPs and QoL outcomes are too commonly overlooked in intervention trials. The purpose of this study was to test the effects of physical and cognitive training on NPs and QoL in MCI. Methods: Baseline data from an MCI court (N = 93, mean age 74.9 ± 4.7) enrolled in the Train the Brain (TtB) study were collected. Subjects were randomized in two groups: a group participated to a cognitive and physical training program, while the other sticked to usual standard care. Both groups underwent a follow-up re-evaluation after 7 months from baseline. NPs were assessed using the Neuropsychiatric Inventory (NPI) and QoL was assessed using Quality of Life-Alzheimer’s Disease (QOL-AD) scale. Results: After 7 months of training, training group exhibited a significant reduction of NPs and a significant increase in QOL-AD with respect to no-training group (p = 0.0155, p = 0.0013, respectively). Our preliminary results suggest that a combined training can reduce NPs and improve QoL. Conclusions: Measuring QoL outcomes is a potentially important factor in ensuring that a person with cognitive deficits can ‘live well’ with pathology. Future data from non-pharmacological interventions, with a larger sample and a longer follow-up period, could confirm the results and the possible implications for such prevention strategies for early cognitive decline