Myxoid glioneuronal tumor: Histopathologic, neuroradiologic, and molecular features in a single center series.

BACKGROUND: Myxoid glioneuronal tumor (MGT) is a benign glioneuronal neoplasm recently introduced in the World Health Organization (WHO) classification of the central nervous system (CNS) tumors. MGTs are typically located in the septum pellucidum, foramen of Monro or periventricular white matter of the lateral ventricle. They were previously diagnosed as dysembryoplastic neuroepithelial tumors (DNT), showing histological features almost indistinguishable from classical cortical DNT. Despite that, MGTs have been associated with a specific dinucleotide substitution at codon 385 in the platelet-derived growth factor receptor alpha (PDGFRA) gene, replacing a lysine residue with either leucine or isoleucine (p. LysK385Leu/Iso). This genetic variation has never been described in any other CNS tumor. MATERIALS AND METHODS: Thirty-one consecutive tumors, previously diagnosed as DNTs at the Meyer Children's Hospital IRCCS between January 2010 and June 2021 were collected for a comprehensive study of their clinical, imaging, pathological features, and molecular profile. RESULTS: In six out of the thirty-one tumors we had previously diagnosed as DNTs, we identified the recurrent dinucleotide mutation in the PDGFRA. All six tumors were typically located within the periventricular white matter of the lateral ventricle and in the septum pellucidum. We then renamed these lesions as MGT, according to the latest WHO CNS classification. In all patients we observed an indolent clinical course, without recurrence. CONCLUSION: MGT represent a rare but distinct group of neoplasm with a typical molecular profiling, a characteristic localization, and a relative indolent clinical course.

Characteristics of viral pneumonia in the COVID-19 era: an update.

Influenza virus, rhinovirus, and adenovirus frequently cause viral pneumonia, an important cause of morbidity and mortality especially in the extreme ages of life. During the last two decades, three outbreaks of coronavirus-associated pneumonia, namely Severe Acute Respiratory Syndrome, Middle-East Respiratory Syndrome, and the ongoing Coronavirus Infectious Disease-2019 (COVID-19) were reported. The rate of diagnosis of viral pneumonia is increasingly approaching 60% among children identified as having community-acquired pneumonia (CAP). Clinical presentation ranges from mild to severe pneumonitis complicated by respiratory failure in severe cases. The most vulnerable patients, the elderly and those living with cancer, report a relevant mortality rate. No clinical characteristics can be useful to conclusively distinguish the different etiology of viral pneumonia. However, accessory symptoms, such as anosmia or ageusia together with respiratory symptoms suggest COVID-19. An etiologic-based treatment of viral pneumonia is possible in a small percentage of cases only. Neuraminidase inhibitors have been proven to reduce the need for ventilatory support and mortality rate while only a few data support the large-scale use of other antivirals. A low-middle dose of dexamethasone and heparin seems to be effective in COVID-19 patients, but data regarding their possible efficacy in viral pneumonia caused by other viruses are conflicting. In conclusion, viral pneumonia is a relevant cause of CAP, whose interest is increasing due to the current COVID-19 outbreak. To set up a therapeutic approach is difficult because of the low number of active molecules and the conflicting data bearing supportive treatments such as steroids.

Isolation, proliferation and characterization of endometrial canine stem cells.

In the last decade, progenitor cells isolated from dissociated endometrial tissue have been the subject of many studies in several animal species. Recently, endometrial cells showing characteristics of mesenchymal stem cells (MSC) have been demonstrated in human, pig and cow uterine tissue samples. The aim of this study was the isolation and characterization of stromal cells from the endometrium of healthy bitches, a tissue that after elective surgery is routinely discarded. Multipotent stromal cells could be isolated from all bitches enrolled in the study (n = 7). The multipotency of cells was demonstrated by their capacity to differentiate into adipocytic, osteocytic and chondrocytic lineages. Clonogenicity and cell proliferation ability were also tested. Furthermore, gene expression analysis by RT-PCR was used to compare the expression of a set of genes (CD44, CD29, CD34, CD45, CD90, CD13, CD133, CD73, CD31 CD105, Oct4) with adipose tissue-derived MSC. Stromal cells isolated from uterine endometrium showed similar morphology, ability of subculture and plasticity, and also expressed a panel of genes comparable with adipose tissue-derived MSC. These data suggest that endometrial stromal cells fulfil the basic criteria proposed by the "Mesenchymal and Tissue Stem Cell Committee of the International Society for Cellular Therapy" for the identification of mesenchymal stem cells. Although endometrial mesenchymal stem cells (EnMSC) showed a lower replicative ability in comparison with adipose tissue-derived MSC, they could be considered a cell therapeutic agent alternative to adipose tissue or bone marrow-derived MSC in dog.

Blood and sputum biomarkers in COPD and asthma: a review.

Chronic obstructive pulmonary disease (COPD) and asthma are lung inflammatory diseases that represent major public health problems. The primary, and often unique, method to evaluate lung function is spirometry, which reflects disease severity rather than disease activity. Moreover, its measurements strictly depend on patient's compliance, physician's expertise and data interpretation. The limitations of clinical history and pulmonary function tests have encouraged focusing on new possible tracers of diseases. The increase of the inflammatory response in the lungs represents an early pathological event, so biological markers related to inflammation may play key roles in earlier diagnosis, evaluation of functional impairment and prognosis. Biomarkers are measurable indicators associated with the presence and/or severity of a biological or pathogenic process, which may predict functional impairment, prognosis and response to therapy. The traditional approach based on invasive techniques (bronchoalveolar lavage and biopsies) may be replaced, at least in part, by using less invasive methods to collect specimens (sputum and blood), in which biomarkers could be measured. Proteomics, by the association between different protein profiles and pathogenic processes, is gaining an important role in pulmonary medicine allowing a more precise discrimination between patients with different outcomes and response to therapy. The aim of this review was to evaluate the use of biomarkers of airway inflammation in the context of both research and clinical practice.

A new method to evaluate the residual activity in patients undergoing (131)I thyroid therapy.

The radioiodine administration is a standard therapeutic approach to both benign thyroid diseases, such as hyperthyroidism, and carcinomas. The high administered (131)I activities are of radiation protection concern, due to relevant patient residual contamination. The aim of this work was to develop a new procedure based on external radiometric surveys and on a mathematical model in order to estimate the (131)I activity in patients undergoing hyperthyroidism radioiodine therapy. In the first stage of this study, a suitable detector was chosen and its response vs. activity was characterized. The experimental verification was performed measuring the ambient dose equivalent rate from patients receiving radioiodine administration. The results confirm the reliability of the proposed method, as shown by the slight differences between the administered activities and the ones calculated from external measurements. Furthermore, the same procedure was applied to detect the percentage residual activity in patients at two preset time intervals: 4 hours and 4 days after the radioiodine administration. The obtained results clearly highlight that the method can ensure a level of reliability compatible with the radiation protection purposes.

High prevalence of gluten sensitivity in a cohort of patients with undifferentiated connective tissue disease.

OBJECTIVES: The aim of this study was to investigate if co-morbid conditions as hepatitis C virus infection and celiac disease may be associated to undifferentiated connective tissue disease. METHODS: We studied retrospectively and prospectively 52 patients with diagnosis of undifferentiated connective tissue disease, subdivided, according to Vaz criteria, in systemic lupus erythematosus, systemic sclerosis and Sjögren's syndrome-like subgroups. Serological markers of celiac disease as anti-gliadin, anti-endomysium and anti-tissue transglutaminase antibodies were investigated. An esophagogastroduodenoscopy with duodenal biopsy and histological examination was proposed to patients with positive celiac disease serology. In addition antibodies directed to hepatitis C virus and total IgA-antibodies were investigated. RESULTS: Six patients (11,5%) were positive for celiac disease serological tests although two of them were asymptomatic. Four patients underwent an esophagogastroduodenoscopy, showing total or subtotal villous atrophy at duodenal biopsies. Hepatitis C virus serology was negative in all patients and none had IgA deficiency. 83% of celiac patients showed a scleroderma-like phenotype. We observed a statistically higher incidence of autoimmune symptoms in patients with gluten sensitivity. Fatigue and myalgia regressed early after the beginning of gluten-free diet. CONCLUSIONS: In our cohort of patients the prevalence of celiac disease was higher than that reported in the general population. We believe that all patients with diagnosis of undifferentiated connective tissue disease, especially those with a systemic sclerosis-like presentation, should be investigated for celiac disease, even in absence of gastrointestinal symptoms. Gluten-free diet should be early recommended to all patients having undifferentiated connective tissue disease and gluten sensitivity.

Focal dysplasia of the cerebral cortex and infantile spasms associated with somatic 1q21.1-q44 duplication including the AKT3 gene.

Somatic and germline duplications or activating mutations of AKT3 have been reported in patients with hemimegalencephaly and megalencephaly. We performed array comparative genomic hybridization on brain tissue and blood in 16 consecutive patients with symptomatic epilepsy due to focal or multilobar malformations of cortical development who underwent surgical treatment of epilepsy. One patient with infantile spasms and a dysplastic left frontal lobe harboured a somatic trisomy of the 1q21.1-q44 chromosomal region, encompassing the AKT3 gene, in the dysplastic brain tissue but not in blood and saliva. Histopathology revealed severe cortical dyslamination, a thin cortex in the premotor area with microgyri and microsulci, immature neurons with disoriented dendrites and areas of cortical heterotopia in the sub-cortical white matter. These cytoarchitectural changes are close to those defining type Ib focal cortical dysplasia. Immunohistochemistry in brain specimens showed hyperactivation of the PI3K/AKT/mTOR pathway. These findings indicate that AKT3 upregulation may cause focal malformations of cortical development. There appears to be an etiologic continuum between hemimegalencephaly and focal cortical dysplastic lesions. The extent of brain malformations due to AKT3 upregulation may be related to the embryonic stage when the post-zygotic gene alteration occurs.

Comparative safety profiles of intravitreal bevacizumab, ranibizumab and pegaptanib: the analysis of the WHO database of adverse drug reactions.

PURPOSE: The purpose of this study is to conduct a comparative analysis of the suspected adverse drug reactions (ADRs) associated with intravitreal bevacizumab, ranibizumab and pegaptanib in the WHO database in order to have a real-life information on these drugs, which now is only based on data coming from clinical trials. METHODS: ADR reports for intravitreal use of bevacizumab, ranibizumab and pegaptanib from January 2002 to December 2012 were selected from the WHO-VigiBase. Reporting odds ratio (ROR) with confidence interval of 95 % and p value was calculated. The analysis was performed for drug-reaction pairs. The Medical Dictionary for Regulatory Activities (MedDRA) terminology for ADRs was used. RESULTS: The analysis was performed on 3180 reports corresponding to 7753 drug-reaction pairs. Significant RORs for endophthalmitis and uveitis (1.90, 95 % confidence interval (CI) 1.48-2.43, and 10.62, 6.62-17.05, respectively) were retrieved for bevacizumab, and cerebrovascular accident and myocardial infarction produced significant ROR (1.54, 1.14-2.10 and 1.73, 1.18-2.53, respectively) for ranibizumab. Pegaptanib was significantly associated with visual impairment (1.98, 1.12-3.5, p = 0.02), nausea (3.29, 1.57-6.86, p < 0.001), vomiting (2.91, 1.2-7.07, p = 0.01) and drug hypersensitivity (8.75, 3.1-24.66, p < 0.001). CONCLUSIONS: Our data showed an elevated disproportionality for cardiovascular ADRs in patients treated with ranibizumab and for infective ocular reactions in those treated with bevacizumab. No relevant safety issues were identified for pegaptanib. These findings suggest bevacizumab as a suitable choice for AMD therapy due to its effectiveness similar to that of ranibizumab, its favourable safety profile and for its lower cost.

Macrophages commit postnatal endothelium-derived progenitors to angiogenesis and restrict endothelial to mesenchymal transition during muscle regeneration.

The damage of the skeletal muscle prompts a complex and coordinated response that involves the interactions of many different cell populations and promotes inflammation, vascular remodeling and finally muscle regeneration. Muscle disorders exist in which the irreversible loss of tissue integrity and function is linked to defective neo-angiogenesis with persistence of tissue necrosis and inflammation. Here we show that macrophages (MPs) are necessary for efficient vascular remodeling in the injured muscle. In particular, MPs sustain the differentiation of endothelial-derived progenitors to contribute to neo-capillary formation, by secreting pro-angiogenic growth factors. When phagocyte infiltration is compromised endothelial-derived progenitors undergo a significant endothelial to mesenchymal transition (EndoMT), possibly triggered by the activation of transforming growth factor-ß/bone morphogenetic protein signaling, collagen accumulates and the muscle is replaced by fibrotic tissue. Our findings provide new insights in EndoMT in the adult skeletal muscle, and suggest that endothelial cells in the skeletal muscle may represent a new target for therapeutic intervention in fibrotic diseases.

Allogeneic adipose tissue-derived mesenchymal stem cells in combination with platelet rich plasma are safe and effective in the therapy of superficial digital flexor tendonitis in the horse.

Overstrain tendonitis are common pathologies in the sport horses. Therapeutic approaches to tendon healing do not always result in a satisfactory anatomical and functional repair, and healed tendon is often characterized by functional impairment and high risk of reinjury. Recently, mesenchymal stem cells (MSCs) and platelet rich plasma (PRP) have been proposed as novel therapeutic treatments to improve the tendon repair process. MSCs are multipotent, easy to culture and being originated from adult donors do not pose ethical issues. To date, autologous MSCs have been investigated mainly in the treatment of large bone defects, cardiovascular diseases, osteogenesis imperfecta and orthopaedic injuries both in human and veterinary medicine. The clinical applications in which autologous MSCs can be used are limited because patient-specific tissue collection and cell expansion require time. For clinical applications in which MSCs should be used right away, it would be more practical to use cells collected from a donor, expanded in vitro and banked to be readily available when needed. However, there are concerns over the safety and the efficacy of allogeneic MSCs. The safety and efficacy of a therapy based on the use of allogeneic adipose tissue-derived mesenchymal stem cells (ASCs) associated to platelet rich plasma (PRP) were evaluated in 19 horses affected by acute or subacute overstrain superficial digital flexor tendonitis (SDFT). The application of allogeneic ASCs neither raised clinical sign of acute or chronic adverse tissue reactions, nor the formation of abnormal tissue in the long-term. After a follow-up of 24 months, 89.5% horses returned to their previous level of competition, while the reinjury rate was 10.5%, comparable to those recently reported for SDFT treated with autologous bone marrow derived MSCs. This study suggests that the association between allogeneic ASCs and PRP can be considered a safe and effective strategy for the treatment of SDF tendonitis in the horse.

Splenic marginal zone lymphoma in a HIV-1 infected patient: evidence favouring a pathogenetic role of HIV-1 itself in the lymphomagenesis.

A rare case of splenic marginal zone lymphoma (SMZL) in a human immunodeficiency virus (HIV)-1 infected patient is described. As an association between SMZL and viral infections has been reported, the presence of the hepatitis C virus and HIV-1 genomes was evaluated. Only HIV-1 DNA levels were detected in enriched splenic B lymphocytes, suggesting a HIV-1 involvement in lymphomagenesis.

A woman with a solitary pulmonary nodule: is it a lung cancer?

BACKGROUND: Solitary pulmonary nodules present a real challenge for physicians. Due to the clinical implications and prognosis of a certain diagnosis, it should be pursued with any cost; a clear definition is not always simple and further investigations are often necessary to exclude the possibility of a malignancy. A diagnostic path must be followed and the clinical hypothesis should be reconsidered on the basis of the new information provided by the tests, always keeping in mind their limits! Sometimes only the surgical resection permits a definitive diagnosis. A 68 year-old non-smoker female with a pulmonary solitary nodule highly suspicious to be malignant at the chest CT, performed a FBS with BAL, negative for neoplastic cells and for infective agents, and a CT guided pulmonary biopsy that was inconclusive. The patient underwent then a video-thoracoscopic atypical lung resection that demonstrated the reactive nature of the lesion, definitely excluding the presence of a malignancy.

Necdin enhances muscle reconstitution of dystrophic muscle by vessel-associated progenitors, by promoting cell survival and myogenic differentiation.

Improving stem cell therapy is a major goal for the treatment of muscle diseases, where physiological muscle regeneration is progressively exhausted. Vessel-associated stem cells, such as mesoangioblasts (MABs), appear to be the most promising cell type for the cell therapy for muscular dystrophies and have been shown to significantly contribute to restoration of muscle structure and function in different muscular dystrophy models. Here, we report that melanoma antigen-encoding gene (MAGE) protein necdin enhances muscle differentiation and regeneration by MABs. When necdin is constitutively overexpressed, it accelerates their differentiation and fusion in vitro and it increases their efficacy in reconstituting regenerating myofibres in the α-sarcoglycan dystrophic mouse. Moreover, necdin enhances survival when MABs are exposed to cytotoxic stimuli that mimic the inflammatory dystrophic environment. Taken together, these data demonstrate that overexpression of necdin may be a crucial tool to boost therapeutic applications of MABs in dystrophic muscle.

Human neutrophil peptides sputum levels in symptomatic smokers and COPD patients.

BACKGROUND AND OBJECTIVES: Human Neutrophil Peptides (HNP) are major neutrophils' products which may contribute to the airway inflammation and lung remodelling during chronic obstructive pulmonary disease (COPD). We aimed to assess whether HNP sputum concentrations could be used as indicators of airway inflammation and progression towards pulmonary functional impairment, and correlate with the degree of airways obstruction. MATERIALS AND METHODS: We measured, by ELISA tests, HNP concentrations from 37 symptomatic smokers and 34 COPD patients. All participants underwent pulmonary function tests. Sputum samples were collected at the enrolment, and 6 months after smoking cessation. Differences between groups and correlation coefficients between variables were determined using non parametric tests. RESULTS: Sputum HNP concentrations were higher in COPD patients as compared to symptomatic smokers (14 +/- 1.5 microg/ml vs 1.6 +/- 0.4 microg/ml; p < 0.0001). Among COPD patients HNP concentrations were higher in individuals with severe obstruction than in patients with mild to moderate COPD (19.9 +/- 2.3 microg/ml vs 10.3 +/- 0.8 microg/ml, p = 0.003). A negative correlation was observed between HNP levels and FEV1 (rho = -0.38, p = 0.02), and FEV1/FVC (rho = -0.42, p = 0.01). No differences were found in HNP levels before and after 6 months of smoking withdrawal (1.1 microg/ml +/- 0.3 vs 1.1 microg/ml +/- 0.3 for symptomatic smokers, p = 0.9, and 14.4 microg/ml +/- 1 vs 16 microg/ml +/- 1.1 for COPD, p = 0.6). DISCUSSION: Sputum levels of HNP may represent a marker of severity of functional impairment in COPD. Our data support the hypothesis that HNP may have a role in smoking- and COPD-related lung inflammation.

A thoracic mass infiltrating the chest wall.

A case of thoracic mass infiltrating the chest wall mimicking a pulmonary invasive neoplasm is reported. Differential diagnosis and characteristic radiological and histological imaging had a decisive role in the case management. Actinomycosis is caused by a gram-positive, filamentous, microaerophilic bacteria. About 15% of the infections caused by Actinomyces involve the thorax. If not promptly diagnosed and treated thoracic actinomycosis may determine contiguous and systemic involvement. Actinomycosis is an anaerobic-to-microaerophilic bacteria and direct identification and isolation are difficult to obtain. In depth discussion diagnostic and therapeutic features are described in this report.

Prevalence of heavy smokers in the year 2000 in the province of Varese, Italy.

BACKGROUND: Knowing the prevalence of heavy smokers (HS) by gender and age is a pre-requisite for bringing into effect public health measures against smoking-related diseases. Smoking prevalence data is available for the Italian Regions, however it is generally unknown for the Italian Provinces. METHODS: In the year 2000 a survey of smoking prevalence was conducted by 47 general practitioners (GPs), by personal interview, in a large sample of the Varese Province population 45-74 years of age (28,034 subjects; 13,528 men, 14,506 women). Each surveyed subject was categorised either as ever HS (current/former smoker of at least 10 pack-years) or as non HS. The information on smoking habit collected by the GPs was anonymously pooled for analysis. Prevalence figures of smoking were tabulated by gender and by 5-year age-strata. RESULTS: In the population 45-74 years of age the percentage of ever HS overall was 22.3% (34.4% of men; 11.0% of women). The prevalence of ever HS in both sexes combined progressively decreased with advancing age, from 23.6% (45-49 year stratum) to 19.5% (70-74 year stratum). Current HS were 24.5% of men and 9.5% of women. CONCLUSIONS: The year 2000 survey on smoking habit, showing 22.3% prevalence of ever HS in age range 45-74 years, is the first conducted in the Varese Province using a large population sample. The data on heavy cigarette smoking presented in this paper, stratified by gender and age, may be used to monitor changes in the smoking habit and in the incidence of smoking-related illnesses at the provincial level.

Osler-Rendu-Weber syndrome: congenital arteriovenous intrapulmonary fistula treated using a percutaneous Amplatzer plug.

Pulmonary arteriovenous fistulas (PAVFs) are rare vascular malformations (PAVMs) of the lung that could lead to severe hypoxiemia due to right-to-left intrapulmonary shunts. They may occur as isolated entities or associated with Osler-Rendu-Weber syndrome or hereditary haemorrhagic telangiectasia (HHT). We report a case of a 70 years old woman with Rendu-Osler-Weber disease and a large arteriovenous malformation involving the left pulmonary artery. We describe the successful transcatheter occlusion of the PAVF using an Amplatzer vascular plug. This work is an attempt to focus the attention on pulmonary arteriovenous malformations and on percutaneous treatment as an alternative to surgery, that consists of a conservative lung resection.

Equine adipose-tissue derived mesenchymal stem cells and platelet concentrates: their association in vitro and in vivo.

Equine mesenchymal stem cells (MSC) are of particular interest both for basic research and for the therapeutic approach to musculoskeletal diseases in the horse. Their multilineage differentiation potential gives them the capability to contribute to the repair of tendon, ligament and bone damage. MSCs are also considered a promising therapeutic aid in allogeneic cell transplantation, since they show low immunogenicity and immunomodulating functions.Adipose tissue-derived adult equine stem cells (AdMSC) can be isolated, expanded in vitro and then inoculated into the damaged tissue, eventually in the presence of a biological scaffold. Here we report our preliminary experience with adipose-derived mesenchymal stem cells in allogeneic cell-therapy of tendonitis in the horse. MSCs, derived from visceral adipose tissue, were grown in the presence of autologous platelet lysate and characterized for their differentiation and growth potential. Expanded AdMSC were inoculated into the damaged tendon after their dispersion in activated platelet-rich plasma (PRP), a biological scaffold that plays an important role in maintaining cells in defect sites and contributes to tissue healing. Fourteen out of sixteen treated horses showed a functional recovery and were able to return to their normal activity.