Management of Severe Asthma in Eosinophilic Granulomatosis with Polyangiitis with Interleukin-5-Targeted Therapies: Current Status and Report of Two Cases

Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic disorder characterized by peripheral eosinophilia, severe eosinophilic asthma, sinusitis, transient pulmonary infiltrates, and features of medium/small-vessel vasculitis. EGPA belongs to the group of anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitides, although only 30 to 40% of patients display ANCA positivity, which is mainly of myeloperoxidase (MPO) specificity. Particularly, ANCA-positive patients typically show vasculitic features. Interleukin (IL)-5 has been demonstrated to play a crucial role in determining eosinophilic airway inflammation in EGPA patients. Specifically, maturation, activation, and survival of eosinophils especially depend on IL-5 availability. Therefore, blocking IL-5 biological activity may be a rewarding strategy for control of eosinophilic inflammation. Several monoclonal antibodies with the ability to interfere with the biological activity of IL-5 have been developed, namely, mepolizumab, reslizumab, and benralizumab. Here, we discuss the role of these drugs in the management of severe eosinophilic asthma in the context of EGPA and report the outcome of two EGPA patients with severe eosinophilic asthma treated at our outpatient clinic

Neutron diffraction in gemology: Single-crystal diffraction study of brazilianite, NaAl3(PO4)(2)(OH)(4)

The chemical composition and the crystal structure of a gem-quality brazilianite from the Telírio pegmatite, near Linópolis, Minas Gerais, Brazil, [NaAl3(PO4)2(OH)4, a = 11.2448(5) Å, b = 10.1539(6) Å, c = 7.1031(3) Å, β = 97.351(4)°, V = 804.36(7) Å3, space group P21/n, Z = 4], have been reinvestigated by means of electron microprobe analysis in wavelength-dispersive mode, single-crystal X-ray and neutron diffraction. The chemical analysis shows that brazilianite from Telírio Claim approaches almost ideal composition. The neutron anisotropic structural refinement was performed with final agreement index R1 = 0.0290 for 211 refined parameters and 2844 unique reflections with Fo > 4σ(Fo), the X-ray refinement led to R1 = 0.0325 for 169 refined parameters and 2430 unique reflections with Fo > 4σ(Fo). The building-block units of the brazilianite structure consist of chains of edge-sharing AlO4(OH)2 and AlO3(OH)3 octahedra. Chains are connected, via corner-sharing, by P-tetrahedra to form a three-dimensional framework, with Na atoms located in distorted cavities running along [100]. Five independent H sites were located, here labeled as H(1), H(2a), H(2b), H(3), and H(4). The configuration of the OH groups, along with the complex hydrogen-bonding scheme, are now well defined. The O-H distances corrected for "riding motion" range between ~0.992 and ~1.010 Å, the O···O distances between ~2.67 and ~2.93 Å, and the O-H···O angles between ~151° and ~174°. The H(2a) and H(2b) are only ~1.37 Å apart and mutually exclusive (both with site occupancy factor of 50%). The differences between the crystal structure of brazilianite and wardite [ideally NaAl3(PO4)2(OH)4·2H2O] are discussed. This work fulfills the need for accurate crystal-chemical data for this gem mineral

Performance of a protein extracted from potatoes for fining of white musts

In this study, the potentiality of Patatin (P), a protein extracted from potato, as must fining agent was investigated on musts obtained from two South Italy grape cultivars (Falanghina and Greco). Besides P, fining agents as bentonite (B) and potassium caseinate (C) were assayed at different concentrations. The rate of sedimentation, the decline of turbidity during time, the absorbance at 420 nm, the GRP (grape reaction products) and hydroxycinnamic acids (HCA) concentrations were determined. The comparative trials showed that P is a suitable fining agent to prevent browning and decrease haze during must settling because its effect on grape phenolics, brown pigments and turbidity is comparable and/or better than that detected for C. Its use as single fining agent or in combination with B depends on must characteristics

Combined photodynamic therapy and intravitreal bevacizumab for idiopathic polypoidal choroidal vasculopathy: one-year follow-up

Abstract OBJECTIVE: To report the efficacy and safety of combined photodynamic therapy (PDT) and intravitreal bevacizumab (IVB) injection in the treatment of idiopathic polypoidal choroidal vasculopathy (IPCV). MATERIAL AND METHODS: A prospective case series of 10 eyes of 10 consecutive patients affected by IPCV with subfoveal involvement. PDT plus IVB (1.25 mg/0.05 mL) injection two weeks later was performed in all patients. Two adjunctive injections of bevacizumab were scheduled at four and eight weeks after the initial treatment. Best-corrected visual acuity (BCVA), fluorescein and indocyanine green angiographies, and optical coherence tomography were obtained at baseline, and at one, three, six, nine, and 12 months. RESULTS: The combined treatment led to an improvement of both neurosensory detachment and pigmented epithelial detachment in all eyes, with a decrease of exudation and regression of macular thickness, which remained stable to the end of follow-up. However, BCVA remained stable over the 12 months of follow-up. CONCLUSION: These findings demonstrate that PDT/IVB combined therapy is able to achieve morphologic stabilization of the IPCV lesion, through a rapid decrease of macular thickness and regression of the size of polypoidal vascular lesion

Disappointing long-term results of the artificial anal sphincter for faecal incontinence

Faecal incontinence can severely affect quality of life, but as it has no influence on life expectancy, the long-term efficacy of any treatment must be taken into account.Most reports on new treatments for faecal incontinence describe short-term results and are rarely followed by a later review of the same group of patients; the few long-term reviews of traditional surgery are disappointing. The authors evaluated long-term outcome after implantation of an artificial bowel sphincter (ABS) (ActiconTM Neosphincter ABS; American Medical System, Minnetonka, Minnesota, USA) to determine whether the results tend to worsen with time. In the present study, obstructed defaecation was a frequent problem that led several patients to deactivate the pump. Together with the manometric findings of low anal canal resting pressure, even with the device activated, this suggests that the ABSmay function as a passive obstacle to the passage of faeces in the long term, like Thiersch’s sling, rather than as a dynamic sphincter. Furthermore, the ABS, like any foreign matter placed in the human body, may displace or erode, either to the rectum or to the perineum. Overall, the present study shows that the results of anal sphincter replacement using an ABS dynamic prosthesis deteriorate with time and that the long-term results may not be as good as reported previously

COVID-19 and arrhythmia: The factors associated and the role of myocardial electrical impulse propagation. An observational study based on cardiac telemetric monitoring

BACKGROUND: The heart is commonly involved in COVID-19, and rhythm disorders have been largely reported. OBJECTIVE: To evaluate the association of some non-cardiac and cardiac comorbidities and QT dispersion with arrhythmias and their impact on outcomes in hospitalized patients with COVID-19. METHODS: Each patient underwent cardiac telemetry monitoring through the entire hospitalization period, laboratory analyses, 12-lead ECG, and lung imaging examination. Patients with arrhythmia were divided into three groups (bradyarrhythmias, tachyarrhythmias, and tachy- and bradyarrhythmias). RESULTS: Two-hundred patients completed the study (males, 123; mean age, 70.1 years); of these, 80 patients (40%) exhibited rhythm disorders on telemetry. Patients with arrhythmia were older (p < 0.0001), had a greater number of comorbidities (p < 0.0001), higher values of creatinine (p = 0.007), B-type natriuretic peptide (p < 0.0001), troponin (p < 0.0001), C-reactive protein (p = 0.01), ferritin (p = 0.001), D-dimer (p < 0.0001), procalcitonin (p = 0.0008), QT interval (p = 0.002), QTc interval (p = 0.04), and QTc dispersion (p = 0.01), and lower values of sodium (p = 0.03), magnesium (p = 0.04), glomerular filtration rate (p < 0.0001), and hemoglobin (p = 0.008) as compared to patients without arrhythmia. By comparing the three subgroups of patients, no significant differences were found. At multivariate analysis, age [odds ratio (OR) = 1.14 (95% CI: 1.07–1.22); p = 0.0004], coronary artery disease [OR = 12.7 (95% CI: 2.38–68.01); p = 0.005], and circulating troponin [OR = 1.05 (95% CI: 1.003–1.10); p = 0.04] represented risk factors independently associated with arrhythmia. All-cause in-hospital mortality was ∼40-fold higher among patients with arrhythmia [OR = 39.66 (95% CI: 5.20–302.51); p = 0.0004]. CONCLUSION: Arrhythmias are associated with aging, coronary artery disease, subtle myocardial injury, hyperinflammatory status, coagulative unbalance, and prolonged QTc dispersion in patients with COVID-19, and confer a worse in-hospital prognosis. Given its usefulness, routinary use of cardiac telemetry should be encouraged in COVID wards

GWAS-associated Variants, Non-genetic Factors, and Transient Transcriptome in Multiple Sclerosis Etiopathogenesis: a Colocalization Analysis [preprint]

A clinically actionable understanding of multiple sclerosis (MS) etiology goes through GWAS interpretation, prompting research on new gene regulatory models. Our previous works on these topics suggested a stochastic etiologic model where small-scale random perturbations could eventually reach a threshold for MS onset and progression. A new sequencing technology has mapped the transient transcriptome (TT), including intergenic RNAs, and antisense intronic RNAs. Through a rigorous colocalization analysis, here we show that genomic regions coding for the TT were significantly enriched for both MS-associated GWAS variants, and DNA binding sites for molecular transducers mediating putative, non-genetic, etiopathogenetic factors for MS (e.g., vitamin D deficiency, Epstein Barr virus latent infection, B cell dysfunction). These results suggest a model whereby TT-coding regions are hotspots of convergence between genetic ad non-genetic factors of risk/protection for MS (and plausibly for other complex disorders). Our colocalization analysis also provides a freely available data resource at www.mscoloc.com for future research on transcriptional regulation in MS

Ascariasis in a 75-year-old man with small bowel volvulus: a case report

Background: Ascaris lumbricoides and Ascaris suum are the most common soil-transmitted helminths of humans and pigs, respectively. The zoonotic potential of A. suum has been a matter of debate for decades. This study was aimed to present a case of human ascariasis caused by A. suum in southern Italy. Case presentation: A 75-year-old man presented to the department of surgery in Avellino (southern Italy) complaining of abdominal pain and vomiting. Physical examination revealed bloating and abdominal tenderness. A computed tomography scan showed air-fluid levels and small bowel distension. During exploratory laparotomy a small bowel volvulus with mesenteritis was evident and surprisingly an intraluminal worm was detected. The worm was removed with a small enterotomy and identified as an adult female of A. suum based on morphological and molecular analysis. Faecal examination revealed the presence of unfertilized Ascaris eggs with an intensity of 16 eggs per gram (EPG) of faeces. The patient was treated with mebendanzole 100 mg twice a day for 3 days. The post-operative course was regular with re-alimentation after 3 days and discharge after 12 days. Conclusions: This report shows as A. suum can function as a relevant agent of human zoonosis. Therefore, in patients with bowel obstruction with no evident aetiology a helminthic infestation should be considered for an accurate diagnosis, especially in patients living in rural areas.Fil: Romano, Giovanni. Frieri-Criscuoli Hospital; ItaliaFil: Pepe, Paola. Università degli Studi di Napoli Federico II; ItaliaFil: Cavallero, Serena. Università di Roma; ItaliaFil: Cociancic, Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Estudios Parasitológicos y de Vectores. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Estudios Parasitológicos y de Vectores; ArgentinaFil: Di Libero, Lorenzo. Frieri-Criscuoli Hospital; ItaliaFil: Grande, Giovanni. Frieri-Criscuoli Hospital; ItaliaFil: Cringoli, Giuseppe. Università degli Studi di Napoli Federico II; ItaliaFil: D'Amelio, Stefano. Università di Roma; ItaliaFil: Rinaldi, Laura. Università degli Studi di Napoli Federico II; Itali

Dyskurs (post)konwencjonalnej tożsamości wobec merkantylistycznej natury globalizującego się świata

In this article I described the idea of globalization, but I abandoned a strictly scientific analysis and treated the subject more contemplatively. I described not only the process, but also the values (connected with the culture of instant gratification, globalization and the cultural homogenization) and the orientation connected with it (consumerism, commoditization of human life) which shape the surrounding reality as well as ourselves. The question of identity, which is constantly shaping, is significant in this context. It is, just as globalization, fluid, unspecified and ambivalent. I endeavour to prove the hypotheses by adducing sociological, cultural and philosophical classic writers. The very last ones – fairly unexpectedly – become crucial to me and they let me analyse the human nature in postmodern reality holistically

Prediction of SARS-CoV-2-Related Lung Inflammation Spreading by V:ERITAS (Vanvitelli Early Recognition of Inflamed Thoracic Areas Spreading)

Background Coronavirus disease 2019 (COVID-19) can be complicated by interstitial pneu-monia, possibly leading to severe acute respiratory failure and death. Because of variable evolution ranging from asymptomatic cases to the need for invasive ventilation, COVID-19 outcomes cannot be precisely predicted on admission. The aim of this study was to provide a simple tool able to predict the outcome of COVID-19 pneumonia on admission to a low-intensity ward in order to better plan management strategies for these patients. Methods The clinical records of 123 eligible patients were reviewed. The following variables were analyzed on admission: chest computed tomography severity score (CTSS), PaO2/FiO2 ratio, lactate dehydrogenase (LDH), neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio, C-reactive protein (CRP), fibrinogen, D-dimer, aspartate aminotransferase (AST), alanine aminotransferase, alkaline phosphatase, and albumin. The main outcome was the intensity of respiratory support (RS). To simplify the statistical analysis, patients were split into two main groups: those requiring no or low/moderate oxygen support (group 1); and those needing subintensive/intensive RS up to mechanical ventilation (group 2). Results The RS intensity was significantly associated with higher CTSS and NLR scores; lower PaO2/FiO2 ratios; and higher serum levels of LDH, CRP, D-dimer, and AST. After multivariate logistic regression and ROC curve analysis, CTSS and LDH were shown to be the best predictors of respiratory function worsening. Conclusions Two easy-to-obtain parameters (CTSS and LDH) were able to reliably predict a worse evolution of COVID-19 pneumonia with values of &gt;7 and &gt;328 U/L, respectively