Clinical Management of COPD in a Real-World Setting. A Big Data Analysis

ObjectiveThe aim of this study was to evaluate the quality of diagnosis and treatment of COPD using Big Data methodology on the Savana Manager 2.1 clinical platform.Materials and methodsA total of 59,369 patients with a diagnosis of COPD were included from a population of 1,219,749 adults over 40 years of age.ResultsIn total, 78% were men. Spirometry data were available for only 26,453 (43.5%) subjects. Disease severity was classified in 18,172 patients: 4396 mild, 7100 moderate, and 6676 severe, although only 27%, 34%, and 28%, respectively, presented obstructive spirometry. The clinical management of COPD is mainly the responsibility of the primary care and pulmonology departments, while internal medicine and, to a lesser extent, geriatrics also participate. Drug treatment was based on bronchodilators and inhaled corticosteroids (ICS). A marked decline in the use of long-acting beta-2 agonists (LABA) in monotherapy and a slight reduction in ICS/LABA combinations, associated with a long-acting anticholinergic (LAMA) in 74% of cases, were observed. All-cause in-hospital mortality among the overall population was 5.6% compared to 1% of the general population older than 40 years. In total, 35% were admitted to hospital, with an average stay of 6.6 days and an in-hospital mortality rate in this group of 10.74%.DiscussionThis study identifies the main features of an unselected COPD population and the main errors made in the management of the disease.     

Serum IgG Profiling of Toddlers Reveals a Subgroup with Elevated Seropositive Antibodies to Viruses Correlating with Increased Vaccine and Autoantigen Responses

Purpose

The human antibody repertoire forms in response to infections, the microbiome, vaccinations, and environmental exposures. The specificity of such antibody responses was compared among a cohort of toddlers to identify differences between seropositive versus seronegative responses.

Methods

An assessment of the serum IgM and IgG antibody reactivities in 197 toddlers of 1- and 2-years of age was performed with a microfluidic array containing 110 distinct antigens. Longitudinal profiling was done from years 1 to 2. Seropositivity to RNA and DNA viruses; bacteria; live attenuated, inactive, and subunit vaccines; and autoantigens was compared. A stratification was developed based on quantitative variations in the IgG responses. Clinical presentations and previously known genetic risk alleles for various immune system conditions were investigated in relation to IgG responses.

Results

IgG reactivities stratified toddlers into low, moderate, and high responder groups. The high group (17%) had elevated IgG responses to multiple RNA and DNA viruses (e.g., respiratory syncytial virus, Epstein-Barr virus, adenovirus, Coxsackievirus) and this correlated with increased responses to live attenuated viral vaccines and certain autoantigens. This high group was more likely to be associated with gestational diabetes and an older age. Genetic analyses identified polymorphisms in the IL2RB, TNFSF4, and INS genes in two high responder individuals that were associated with their elevated cytokine levels and clinical history of eczema and asthma.

Conclusion

Serum IgG profiling of toddlers reveals correlations between the magnitude of the antibody responses towards viruses, live attenuated vaccines, and certain autoantigens. A low responder group had much weaker responses overall, including against vaccines. The serum antibody screen also identifies individuals with IgG responses to less common infections (West Nile virus, parvovirus, tuberculosis). The characterization of the antibody responses in combination with the identification of genetic risk alleles provides an opportunity to identify children with increased risk of clinical disease.

     

In Vivo Uptake of Rare Earth Metals by Triple-Negative Breast Cancer Cells

Rare earth metals (REM) are a group of 17 chemical elements in the periodic table, namely scandium (Sc), yttrium (Y) and the lanthanides. In relation to atomic volume and geological behavior, the lanthanides are further subdivided into light, medium and heavy REM. They find many applications in the technological field; however, their impact on the human health is still conflicting and, for many aspects, unknown. During a research program carried on 113 cases of female breast cancer, immunohistochemically categorized in Her2-positive (29 cases), Her2-negative (57 cases) and triple negative (27 cases), aimed to evaluate the role of environmental particulate in carcinogenesis by elemental microanalysis, for the first time in literature we have detected a REM uptake, in detail europium (Eu), dysprosium (Dy) and praseodymium (Pr), inside the neoplastic cells belonging to a single triple negative breast cancer. Curiously, the woman affected by this form of malignancy had worked in the ceramic industry, a well-known source of REM, during her life, and she was the one and only patient of our series to be dedicated to this activity. The medical repercussions of our findings are here discussed: in fact, a REM detection in only 1 of 113 examined cases seems to exclude active roles in breast carcinogenesis and discloses new possibilities for therapeutic developments in triple negative breast cancer.     

Heart-hand syndrome

Heart–hand syndromes show substantial clinical and genetic heterogeneity. The unusual case of a patient with a heart–hand syndrome consisting of preaxial polydactylia, postaxial syndactylia, parachute mitral valve, mild subaortic stenosis, and double outlet right ventricle is presented and discussed. The importance of distinguishing Holt–Oram syndrome from its phenocopies and other heart–hand syndromes is underlined.     

Clonality and specificity of cryoglobulins associated with HCV: pathophysiological implications

Background/Aims: Hepatitis C virus (HCV) infection plays a central role in the pathogenesis of mixed cryoglobulinemia through molecular mechanisms which remain to be elucidated. The aim of this study was to investigate the role of antibody responses to HCV in the pathogenesis of cryoglobulinemia through characterization of the anti-HCV specificity and immunochemical characteristics of the immunoglobulins involved in cryoprecipitation.Methods: Sera from 50 consecutive patients with chronic HCV infection (RNA positive) were screened for the presence of cryoglobulins. The two major components of cryoprecipitates, IgM rheumatoid factors and IgG, were separated by high performance liquid chromatography and analyzed for immunochemical composition by immunoblotting and antibody specificity by ELISA and immunoblotting using recombinant HCV proteins and synthetic peptides as antigens.Results: Cryoprecipitates were observed in 27 patients and characterized by immunofixation: 13 (48%) were classified as type II and 14 (52%) as type III. Monoclonal immunoglobulins were detected by immunoblotting in 20 cryoprecipitates: IgM in 14 samples and IgG in 14, which a clear preponderance of IgG3 (). Specificity studies on sera and purified IgM and IgG fractions from cryoprecipitates revealed enrichment in cryoglobulins, predominantly polyclonal IgG1, reactive with the HCV structural proteins, whereas specificities for nonstructural viral proteins were relatively less represented compared to whole serum. No restricted pattern of fine specificity was observed. IgG3 subclass was apparently not involved in HCV nucleoprotein binding.Conclusions: Our findings do not support a direct link between monoclonal cryoglobulins and immune response to HCV. According to the proposed pathogenetic model, HCV infection can induce the formation of cryoprecipitable rheumatoid factors, sustain their production, and eventually lead to monoclonal B-cell expansion through several cooperative mechanisms.     

Increased synthesis and production of prostaglandin E2 by monocytes from drug addicts with AIDS

We analysed the production of prostaglandin E2 (PGE2) by monocytes in 11 drug addicts with AIDS and opportunistic infections and in 13 controls. In three patients and six controls we isolated the PGE2 fraction from culture supernatants of purified monocytes (greater than 95%) incubated in medium containing (3H) arachidonic acid, using silicic acid columns. In two of three patients PGE2-fraction values (21.9 and 21.6 pmol/g protein) were significantly higher than controls (10 +/- 4). In eight AIDS patients and seven controls, PGE2 levels were determined by high-performance liquid chromatography and radioimmunoassay (HPLC and RIA). In three out of eight patients PGE2 levels were markedly higher (736, 419 and 208 pg/ml) than the mean + 2 s.d. values from controls (73 +/- 51). We tested the effect of PGE2 on the production of interleukin-2 by normal phytohemagglutinin-stimulated peripheral blood lymphocytes (PBL). There was a significant suppression of interleukin-2 production by PGE2 released from AIDS monocytes. PGE2 may be one of the factors involved in the severe immune dysfunction associated with AIDS.     

The impact of the SARS‐CoV‐2 infection,with special reference to the hematological setting

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is a disease known from a few months, caused by a recently arisen virus and, consequently, it is little known. The disease has a benign course in most infected subjects (children and young adults), is often symptomatic in adults over the age of 50 and often serious and life threatening in people with comorbidities and the elderly. The few data published on coronavirus disease‐2019 (COVID‐19) in the blood‐oncology field report a serious clinical presentation, a serious course of the disease, and a high mortality rate, as has also been reported for other cancer contexts. The current strategy for treating patients with SARS‐CoV‐2 includes antivirals that are effective against other viral infections and drugs that can moderate the cytokine storm. There is no specific vaccine and consequently all possible precautions must be taken to prevent SARS‐CoV‐2 infection in the areas of oncology, oncohematology, and bone marrow transplantation. In this reviewer's article, we report the information currently available on SARS‐CoV‐2 infection to help young doctors and hematologists to successfully manage patients with COVID‐19.