Diffuse panbronchiolitis in a patient with common variable immunodeficiency: a casual association or a pathogenetic correlation?

Diffuse panbronchiolitis (DPB) is an idiopathic inflammatory disease that seems to have an immunological pathogenesis and that causes a severe progressive suppurative and obstructive respiratory disorder. Common variable immunodeficiency (CVID) is the most common serious primary immunodeficiency and it is often associated with respiratory diseases. Herein, we describe a case of DPB in a 41-year-old man affected by CVID. We examined the patient's lungs, focusing on the characteristics of the inflammatory cells and of the foamy macrophagic nodules typical of DPB. Immunohistochemical typing of the lymphocytic infiltrate showed that B-cells were almost absent, matching the immunological profile of CVID. The case described is the first case reported in the literature of DPB in a patient affected by CVID. Moreover it seems to confirm the correlation between an immunodeficiency status and the development of DPB and provides more information on the accumulation of nodules of foamy macrophages in DPB

Clinical and molecular characterization of patients affected by Beckwith-Wiedemann spectrum conceived through assisted reproduction techniques

The prevalence of Beckwith-Wiedemann spectrum (BWSp) is tenfold increased in children conceived through assisted reproductive techniques (ART). More than 90% of ART-BWSp patients reported so far display imprinting center 2 loss-of-methylations (IC2-LoM), versus 50% of naturally conceived BWSp patients. We describe a cohort of 74 ART-BWSp patients comparing their features with a cohort of naturally conceived BWSp patients, with the ART-BWSp patients previously described in literature, and with the general population of children born from ART. We found that the distribution of UPD(11)pat was not significantly different in ART and naturally conceived patients. We observed 68.9% of IC2-LoM and 16.2% of mosaic UPD(11)pat in our ART cohort, that strongly differ from the figure reported in other cohorts so far. Since UPD(11)pat likely results from post-fertilization recombination events, our findings allows to hypothesize that more complex molecular mechanisms, besides methylation disturbances, may underlie BWSp increased risk in ART pregnancies. Moreover, comparing the clinical features of ART and non-ART BWSp patients, we found that ART-BWSp patients might have a milder phenotype. Finally, our data show a progressive increase in the prevalence of BWSp over time, paralleling that of ART usage in the last decades

Spectrum of mutations in Italian patients with familial hypercholesterolemia: New results from the LIPIGEN study

Background Familial hypercholesterolemia (FH) is an autosomal dominant disease characterized by elevated plasma levels of LDL-cholesterol that confers an increased risk of premature atherosclerotic cardiovascular disease. Early identification and treatment of FH patients can improve prognosis and reduce the burden of cardiovascular mortality. Aim of this study was to perform the mutational analysis of FH patients identified through a collaboration of 20 Lipid Clinics in Italy (LIPIGEN Study). Methods We recruited 1592 individuals with a clinical diagnosis of definite or probable FH according to the Dutch Lipid Clinic Network criteria. We performed a parallel sequencing of the major candidate genes for monogenic hypercholesterolemia (LDLR, APOB, PCSK9, APOE, LDLRAP1, STAP1). Results A total of 213 variants were detected in 1076 subjects. About 90% of them had a pathogenic or likely pathogenic variants. More than 94% of patients carried pathogenic variants in LDLR gene, 27 of which were novel. Pathogenic variants in APOB and PCSK9 were exceedingly rare. We found 4 true homozygotes and 5 putative compound heterozygotes for pathogenic variants in LDLR gene, as well as 5 double heterozygotes for LDLR/APOB pathogenic variants. Two patients were homozygous for pathogenic variants in LDLRAP1 gene resulting in autosomal recessive hypercholesterolemia. One patient was found to be heterozygous for the ApoE variant p.(Leu167del), known to confer an FH phenotype. Conclusions This study shows the molecular characteristics of the FH patients identified in Italy over the last two years. Full phenotypic characterization of these patients and cascade screening of family members is now in progress

Familial hypercholesterolemia: The Italian Atherosclerosis Society Network (LIPIGEN)

BACKGROUND AND AIMS: Primary dyslipidemias are a heterogeneous group of disorders characterized by abnormal levels of circulating lipoproteins. Among them, familial hypercholesterolemia is the most common lipid disorder that predisposes for premature cardiovascular disease. We set up an Italian nationwide network aimed at facilitating the clinical and genetic diagnosis of genetic dyslipidemias named LIPIGEN (LIpid TransPort Disorders Italian GEnetic Network). METHODS: Observational, multicenter, retrospective and prospective study involving about 40 Italian clinical centers. Genetic testing of the appropriate candidate genes at one of six molecular diagnostic laboratories serving as nationwide DNA diagnostic centers. RESULTS AND CONCLUSIONS: From 2012 to October 2016, available biochemical and clinical information of 3480 subjects with familial hypercholesterolemia identified according to the Dutch Lipid Clinic Network (DLCN) score were included in the database and genetic analysis was performed in 97.8% of subjects, with a mutation detection rate of 92.0% in patients with DLCN score 656. The establishment of the LIPIGEN network will have important effects on clinical management and it will improve the overall identification and treatment of primary dyslipidemias in Italy

A case of hypersensitivity pneumonitis in a worker exposed to terephthalic acid in the production of polyethylene terephthalate

Occupational hypersensitivity pneumonitis (OHP) is an interstitial lung disease caused by sensitization to an inhaled antigen. Polyethylene terephthalate (PET) is mainly used for disposable beverage bottles. A clinical case of hypersensitivity pneumonitis (HP) in a 66-year-old patient in the follow-up as a worker formerly exposed to asbestos is presented. At the first visit in 2012 a diagnosis of asbestosis and pleural plaques was formulated. In 2017 the high resolution computed tomography was performed demonstrating a slight progression of the pulmonary fibrosis, while physical examinations revealed inspiratory crackles on auscultation, and lung function tests showed a decreased diffusing capacity for carbon monoxide. The radiological and histological pictures were compatible with HP. From 1992 to 2013 the patient worked in a chemical company that produced PET for disposable beverage bottles. A diagnosis of OHP was made, and the most likely causative agents were terephthalic acid and dimethyl terephthalate. To the best of the authors’ knowledge, this is the first report of an OHP case in PET production

Durum Wheat Bread with a Potentially High Health Value through the Addition of Durum Wheat Thin Bran or Barley Flour

The enrichment of semolina bread with prebiotic ingredients such as β-glucans may exert health-promoting effects. This work presents the results of a general recipe development aimed at improving the nutritional value of bakery products. In this study, increasing amounts (0%, 2%, 5%, 7%, and 10%) of thin bran or barley flour were added into re-milled durum wheat semolina to prepare breads. The technological quality of doughs and breads was investigated. In general, the Farinograph water absorption of flour and dough stability increased with increasing inclusion levels of barley flour or thin bran (up to 73.23% and 18.75 min, respectively), contrarily to the increase of dough development time only in barley inclusion (4.55 min). At the same time, the softening index decreased for almost all of these, except for 2% of thin bran or barley flour inclusion. At Mixograph, mixing time increased (up to 5.13 min) whilst the peak height decreased. The specific volume and hardness of loaf differently decreased for almost all thesis (ranges 12.6–24.0% and 39.4–45.5%, respectively). The other quality parameters remained unchanged compared with semolina bread. After baking, β-glucan levels increased differently at all the inclusion levels (2.35-fold, on average). The breadcrumb color was deep brown, while the crust became lighter in color. The breads contain β-glucans even at low percentages of barley/bran inclusions while maintaining their technological performance. In conclusion, the results show an interesting potential of barley flour or thin bran as ingredients in breadmaking to increase the β-glucans daily intake, but further investigations are needed to achieve improved quality features

Type II congenital pulmonary airway malformation associated with intralobar pulmonary sequestration: report of a case and review of classification criteria

Pulmonary congenital abnormalities are rare disorders including congenital pulmonary airway malformations (CPAM) and pulmonary sequestration (PS). CPAM is a lesion characterized by the presence of anomalous bronchiolar or acinar structures, variable in size, either cystic or not cystic. PS is generally defined as nonfunctioning lung tissue that is not in normal continuity with the tracheobronchial tree and that derives its blood supply from systemic vessels. We describe a case of a baby girl with a very rare association between CPAM type 2 and intralobar pulmonary sequestration (IPS) focusing on the cystic lesions typical of CPAM and on the lymphatic and blood vessels. The cells lining the cysts often were positive for D2-40 (oncofetal protein M2A). Lymphatic endothelial cells, positive for D2-40, were widely present in the lung parenchyma and dilated lymphatic vessels were present also in the inter-alveolar septa. Moreover, we discuss the pathogenesis of CPAM and its classification criteria

Rheumatoid nodule and combined pulmonary carcinoma: topographic correlations; a case report and review of the literature

An association between rheumatoid arthritis (RA) and malignancies has been ascertained and patients with RA appear to be at higher risk of lymphoma and lung cancer. The higher risk of the latter malignancy may be related to rheumatoid interstitial lung disease and immunosuppressive therapies. Herein we illustrate the case of a 59-year-old male smoker affected by RA and treated with cortisone, methotrexate and TNF-α antagonists, who underwent right lower lobectomy for a nodular lesion. On microscopic examination, the lesion consisted of two distinct areas: a central area of fibrinoid necrosis, bordered by histiocytes in a palisaded arrangement, lymphocytes and a 0.4 cm thick peripheral area constituted by a combined small cell anaplastic carcinoma, adenocarcinoma and squamous cell carcinoma. The combination of three histotypes is very rare in such a small tumour. In our case, it may be hypothesized that synchronous, heterogeneous mutations occurred in different type of committed cells or in stem cells, due to the production of cytokines by RA nodule histiocytes and lymphocytes, which are contiguous to the carcinomatous area. Since few studies have evaluated the topographic correlation between tumors and rheumatoid lung lesions, further morphological and molecular studies are needed to clarify this association and the pathogenetic relationship between RA and cancer of the lung