Search

Objective: To evaluate whether the addition of colchicine to standard of care (SOC) results in better outcomes in hospitalized patients with COVID-19. Design: This interventional, multicenter, randomized, phase 2 study, evaluated colchicine 1.5 mg/day added to SOC in hospitalized COVID-19 patients (COLVID-19 trial) and 227 patients were recruited. The primary outcome was the rate of critical disease in 30 days defined as need of mechanical ventilation, intensive care unit (ICU), or death. Results: 152 non-anti-SARS-CoV-2-vaccinated patients (colchicine vs controls: 77vs75, mean age 69.1±13.1 vs 67.9±15 years, 39% vs 33.3% females, respectively) were analyzed. There was no difference in co-primary end-points between patients treated with colchicine compared to controls (mechanical ventilation 5.2% vs 4%, ICU 1.3% vs 5.3%, death 9.1% vs 6.7%, overall 11 (14.3%) vs 10 (13.3%) patients, P=ns, respectively). Mean time to discharge was similar (colchicine vs controls 14.1±10.4 vs 14.7±8.1 days). Older age (>60 years, P=0.025), P/F40 U/L (P60 years) patients with comorbidities are characterized by worse outcome.

In this study, quantitative monitoring of low-frequency (20 kHz) and high-frequency (355 kHz) ultrasound-induced inactivation of Kunitz (KTI) and Bowman-Birk inhibitor (BBI) using RP-HPLC was achieved, and its consistency with a traditional TI activity assay was verified. The effect of TI concentration, ultrasonic frequency, power density and pH on inactivation kinetics of KTI and BBI was explored. Results showed that the pseudo-first-order kinetic rate constants of KTI and BBI were decreased by over 60% when the initial TI concentration was increased from 100 mg/L to 1000 mg/L. Also, the amounts of inactivated KTI and BBI were increased by around 4-fold at the higher TI concentration of 1000 mg/L (20 kHz, 1.71 W/mL and pH 4). The colloidal environment and ultrasonic conditions influenced the secondary and tertiary structure and particle size of TIs in LF-induced inactivation. In comparison, the abovementioned conditions affected the oxidation of methionine and the conformational change of TIs in HF-induced inactivation.

the relationship between physical exercise and gut microbiota has opened new therapeutic frontiers for many inflammatory diseases. However, there is still a lot of uncertainty about how to administer exercise.to review the literature to bridge this gap and examine the relationship between cardiorespiratory fitness (CRF) and microbiota.systematic review.studies involving humans who undergoing exercise programmes of any lengths, intensities, and types were included. The research was carried out through PubMed, Scopus, and Web of Science.the primary outcome was change in gut microbiota composition (α and β-diversity), while the secondary outcome was the CRF level.the 15 studies included (all with PEDro scale=5) used aerobic training alone or combined with resistance exercises. In general, exercise has shown positive effects on the microbiota, influencing the faecal count of some bacterial phyla (in particular Bacteroidetes, Firmicutes, and Proteobacteria), with a weak tendency towards proportionality in relation to training duration and intensity. However, the evidence supporting the exercise effects on the gut microbiota and the relationship with CRF are of low quality.despite the weak evidence in favour of the effects of the practice of physical exercise on the intestinal microbiota, there are still many aspects that need to be explored. In particular, future studies shall have higher quality and methodological rigour, standardize the methods for outcome assessment, and determine type and thresholds of interventions intensity and duration.

Objective To evaluate the diagnostic accuracy of anticarbamylated protein antibodies (CarP), alone and in combination with traditional biomarkers (rheumatoid factor [RF] and anticitrullinated peptide antibodies [ACPA]), in established rheumatoid arthritis (RA). Methods A commercially available enzyme‐linked immunosorbent assay (ELISA) kit was used to assess CarP concentrations in serum samples of 200 established RA and 206 controls (115 healthy donors and 55 patients with other rheumatic diseases). Main outcome measures were sensitivity, specificity, and area under the curve (AUC; 95% confidence interval [CI]). Difference in accuracy was evaluated by comparison of the respective AUCs. Results A serum CarP cut‐off of 1.47 ng/ml or more differentiated patients with RA from controls with 30% sensitivity, 97.1% specificity, and good accuracy (AUC[95%CI] = 0.83[0.79‐0.86], P < 0.0001). However, it showed moderate diagnostic accuracy in seronegative RA patients: sensitivity 17.9%, specificity 96.9%, and AUC (95% CI) = 0.69 (0.63‐0.75). The diagnostic accuracy of CarP_ACPA and CarP_RF combinations was significantly superior to that of ACPA and RF alone (P < 0.0001 and P = 0.015, respectively), but not to that of ACPA_RF combination (P = 0.089) In addition, the CarP_ACPA_RF combination did not improve the diagnostic accuracy of the ACPA_RF combination (AUC mean difference [95% CI] = 0.006 [−0.001 to 0.015], P = 0.10). The number of positive autoantibodies (0, 1, 2, or 3) was not significantly associated with moderate‐severe disease (Disease Activity Score‐28 [DAS‐28] > 3.2) in adjusted multiple regression analysis. Conclusion CarP has good diagnostic accuracy in established RA but not in seronegative RA. The addition of CarP to ACPA and RF alone or in combination does not significantly enhance the diagnostic accuracy of ACPA_RF combination.

Background:Brain-injured patients frequently require tracheostomy, but no technique has been shown to be the gold standard for these patients. We developed and introduced into standard clinical practice an innovative bedside translaryngeal tracheostomy (TLT) technique aided by suspension laryngoscopy (modified TLT). During this procedure, the endotracheal tube is left in place until the airway is secured with the new tracheostomy. This study assessed the clinical impact of this technique in brain-injured patients.Materials and Methods:This is a retrospective analysis of prospectively collected data from adult brain-injured patients who had undergone modified TLT during the period spanning from January 2010 to December 2016 at the Neurointensive care unit, San Gerardo Hospital (Monza, Italy). The incidence of intraprocedural complications, including episodes of intracranial hypertension (intracranial pressure [ICP] >20 mm Hg), was documented. Neurological, ventilatory, and hemodynamic parameters were retrieved before, during, and after the procedure. Risk factors for complications and intracranial hypertension were assessed by univariate logistic analysis. Data are presented as n (%) and median (interquartile range) for categorical and continuous variables, respectively.Results:A total of 199 consecutive brain-injured patients receiving modified TLT were included. An overall 52% male individuals who were 66 (54 to 74) years old and who had an admission Glasgow Coma Scale of 7 (6 to 10) were included in the cohort. Intracerebral hemorrhage (30%) was the most frequent diagnosis. Neurointensivists performed 130 (65%) of the procedures. Patients underwent tracheostomy 10 (7 to 13) days after intensive care unit admission. Short (ie, 20 mm Hg were observed in 11 cases. Overall, the procedure was associated with an increase in ICP from 7 (4 to 10) to 12 (7 to 18) mm Hg (P

We read with great interest the letter by Kawada in which the studies assessing colchicine as a treatment for COVID-19 were reviewed.1 Given its known inhibitory effect on NACHT-LRRPYD-containing protein 3 inflammasome2 and its possible antiviral properties,2 colchicine was hypothesised as a candidate therapy for COVID-19 since the very beginning of the pandemic.3 4 To the best of our knowledge, our observational retrospective study5 reported on the largest number of patients with COVID-19 treated with colchicine (122 consecutive patients), and they were compared with a control group treated with the Standard of Care (SoC, 140 consecutive patients).5 Kawada underlined the effectiveness of colchicine in reducing mortality and the need for non-invasive ventilation, as shown by different studies.5–7 After the hospital discharge, we observed additional deaths in patients treated with colchicine and in those treated with SoC (p=0.25). The long-term analysis of our cohort confirmed the original description of improved survival for patients treated with colchicine (mortality rate at 270 days: colchicine 20% vs SoC 44%; p=0.0001). We would like to point out the statement by Kawada reporting that ferritin and arterial oxygen tension (or pressure) (PaO2 …

We thank Della-Torre et al for their interest on our report on the retrospective, case-control observational study with colchicine in patients hospitalised for severe COVID-19,1 and for rising the really crucial issue of the timing of the therapeutic intervention with anti-inflammatory therapies in this disease.2 Our observations should be interpreted in the scenario of the uncontrolled epidemic that, during March and April 2020, overwhelmed the health system in Lombardy, Italy, with rapid shortage of intensive care unit beds. As pointed out by the authors in other papers, after this period, the severity of the COVID-19 progressively decreased, in parallel with the exhaustion of the epidemic.3 4 The COVID-19 related mortality observed in our study (27.5% in the overall cohort of 262 consecutive cases; 36.4% in the standard of care group, and 15.8% in …

ObjectivesThe outbreak of COVID-19 posed the issue of urgently identifying treatment strategies. Colchicine was considered for this purpose based on well-recognised anti-inflammatory effects and potential antiviral properties. In the present study, colchicine was proposed to patients with COVID-19, and its effects compared with ‘standard-of-care’ (SoC).MethodsIn the public hospital of Esine, northern Italy, 140 consecutive inpatients, with virologically and radiographically confirmed COVID-19 admitted in the period 5–19 March 2020, were treated with ‘SoC’ (hydroxychloroquine and/or intravenous dexamethasone; and/or lopinavir/ritonavir). They were compared with 122 consecutive inpatients, admitted between 19 March and 5 April 2020, treated with colchicine (1 mg/day) and SoC (antiviral drugs were stopped before colchicine, due to potential interaction).ResultsPatients treated with colchicine had a better survival rate as compared with SoC at 21 days of follow-up (84.2% (SE=3.3%)vs63.6% (SE=4.1%), p=0.001). Cox proportional hazards regression survival analysis showed that a lower risk of death was independently associated with colchicine treatment (HR=0.151 (95% CI 0.062 to 0.368), pConclusionThis proof-of-concept study may support the rationale of use of colchicine for the treatment of COVID-19. Efficacy and safety must be determined in controlled clinical trials.

Photocatalysis is an advanced oxidation process which can be used for water purification. Studies on Plug Flow Reactor (PFR) and Continuous Stirred Tank Reactor (CSTR) systems are imperative if photocatalysis is to be used in large-scale applications. Between them, the CSTR system is an obvious choice for studies, because a series of CSTRs is equivalent to a PFR. However, a CSTR often imposes the use of fixed-bed reactors, which dramatically reduces the efficiency of the process. In this work, a dispersed photocatalyst system was combined with CSTR in order to develop an efficient system for continuous operation. We have overcome the problems of filter blockage, the need for premixing and catalyst retrieval at the end of the reaction using micron-sized photocatalyst powder and short sonication time carried out every 30 minutes. Two model pollutants (metanil yellow and rhodamine B) were used for the degradation studies. Variables such as flow-rate, pollutant, and catalyst concentration were also investigated to evaluate the CSTR performance. The results showed that the CSTR system could lead to an increase in degradation of up to 110%, compared to a batch system, and to a continuous operation longer than 42 h without filter blockage or deactivation of the catalyst.

In the past few decades, several studies have used nanoparticles for photocatalytic reactions. For practical applications, the use of nanomaterials may not be advantageous due to the difficulties in removing them from processed liquids, and they also pose possible health risks. We have developed a procedure that uses chitosan to convert nanosized photocatalysts into micron sized materials without losing their efficiency or surface area. Additionally, the synthetic method offers the possibility of adding functionality like macroporosity and doping carbon or gold nanoparticles. The synthesis involves ultrasonic emulsification of tetradecane in an aqueous chitosan solution containing photocatalytic nanoparticles. Tetradecane-core chitosan/photocatalyst composite-shelled microspheres were produced during the ultrasonic emulsification process. Calcination of these microspheres resulted in the formation of carbon doped micron-sized photocatalytic particles with macroporous structure. Detailed characterisations were carried out using dynamic light scattering, zeta potential, SEM, TEM, BET, XRD and XPS measurements. A possible mechanism for the formation of micron-sized photocatalytic particles is proposed. The photocatalytic efficiencies of synthesised microparticles and their reusability through filtration were evaluated and compared with that of starting nanomaterials using two organic dyes as model pollutants. One of the catalysts (gold doped photocatalyst) was also tested for H2S gas removal by adsorption. The regeneration of the adsorbent was also achieved after room temperature photocatalysis. The results indicate that the synthetic procedure can be used to produce macroscale photocatalysts with a size range of 10–20 μm as efficient as the starting nanopowders (size range of 20–50 nm).

Background The main clinical associations of anti-PM/Scl in Systemic Sclerosis (SSc) include calcinosis, joint and muscle involvement, interstitial lung disease (ILD), and, possibly, scleroderma renal crisis (1,2). A possible association of anti-PM/Scl with cancer was reported in single-centre SSc series (2,3), but was never analysed in large multicentre studies. Moreover, the characteristics of malignancies, in particular their temporal association with the onset of SSc, were not explored. Objectives To evaluate the association of anti-PM/Scl with malignancies in a large, international, multicentre cohort. Methods 16 EUSTAR centres provided data on anti-PM/Scl+ SSc patients in their cohorts (cases), and on anti-PM/Scl-negative controls, matched for sex, age at onset (±5 years), cutaneous subset, and disease duration (±24 months). Only SSc patients with age >16 years at disease onset were included in this analysis. Anti-RNA Polymerase3+ patients were not included in controls, given the known association with synchronous cancer. Malignancies diagnosed between 2 years before and after the onset of SSc were defined as “synchronous to the onset of SSc”. Results 123 anti-PM/Scl+ SSc patients and 160 matched anti-PM-Scl- controls (28% anti-Topoisomerase I, 40% anti-centromere, 32% others) were compared (Table 1): anti-Pm/Scl+ patients had a higher prevalence of myositis (p Conclusion: in this EUSTAR multicentre case control-study, the association of anti-Pm/Scl with malignancies in SSc patients could not be confirmed. Patients with older age at SSc onset seems to be at higher risk for synchronous malignancies, regardless the autoantibody status. References [1] Lazzaroni MG, et al. Ann Rheum Dis2018; 77:(Suppl 2),421-422. [2] Bruni C, et al. Rheumatology (Oxford). 2017;56:317-8. [3] Bernal-Bello D, et al. Autoimmun Rev2017;16:461-8. Acknowledgement Authors would like to thank GILS (Gruppo Italiano Lotta Sclerodermia) for the grant to support this project Disclosure of Interests Maria Grazia Lazzaroni: None declared, Stefania Zingarelli: None declared, Jeska de Vries-Bouwstra: None declared, Eric Hachulla Consultant for: Received consulting fees or other remuneration from Actelion, GSK, Pfizer, and Bayer, Elisabetta Zanatta: None declared, Simone Barsotti: None declared, Marie-Elise Truchetet: None declared, Giacomo De Luca Speakers bureau: Pfeizer, Sobi, Vanessa Smith: None declared, Ellen De Langhe: None declared, Roger Hesselstrand: None declared, Francesca Ingegnoli: None declared, Cristian Caimmi: None declared, Silvia Bellando Randone: None declared, Enrico Colombo: None declared, Angela Ceribelli: None declared, Franco Franceschini: None declared, Yannick Allanore Grant/research support from: Inventiva, F Hoffman La-Roche, Sanofi, BMS, Pfizer, Consultant for: Actelion, Bayer, BMS, Boehringer, Roche, Sanofi, Paolo Airo: None declared

Diagnosis of postenteritic reactive arthritis (ReA) is a challenge and might have a broad range of differential diagnoses. A 50-year-old man was referred to our attention because of persistent inflammatory low back pain and asymmetric oligoarthritis. The clinical history was positive for diarrhoea in the previous 3 months. Inflammatory bowel disease, Whipple and celiac diseases were carefully excluded. In addition, serology, stool cultures, biopsies from the upper gastrointestinal tract yielded negative results for infections. A presumptive diagnosis of ReA was done and a non-steroidal anti-inflammatory drug trial prescribed. Persistence of symptoms prompted us for a second look of the colon. Biopsy collected from the terminal ileum were cultured and surprisingly colonies of Hafnia alvei, a rod-shaped Enterobacteriaceae, were detected. Treatment with ciprofloxacin leads to fast symptoms resolution. Although enterocolitis from H. alvei has been rarely reported, the culture of intestinal specimens might be recommended in the work-up of patients with suspected postenteritic ReA.

The term congenital hypopigmentary disorders refers to a wide group of heterogeneous hereditary diseases, clinically characterized by inborn pigmentary defects of the iris, hair, and/or skin. They include Gray Hair Syndromes (GHSs), a rare group of autosomal recessive genodermatosis hallmarked by inborn silvery gray hair. GHSs encompass Griscelli, Chediak–Higashi, Elejalde, and Cross syndromes, which are all characterized by a broad spectrum of severe multisystem disorders, including neurological, ocular, skeletal, and immune system impairment. In this manuscript, we describe in detail the clinical, trichoscopic, and genetic features of a rare case of Griscelli syndrome; moreover, we provide an overview of all the GHSs known to date. Our report highlights how an accurate clinical examination with noninvasive methods, like trichoscopy, may play a crucial rule in diagnosis of rare and potentially lethal genetic syndromes such as Griscelli syndrome, in which timely diagnosis and therapy may modify the clinical course, quality of life, and likelihood of survival.

Congenital sensorineural hearing loss may occur in association with inborn pigmentary defects of the iris, hair, and skin. These conditions, named auditory-pigmentary disorders (APDs), represent extremely heterogeneous hereditary diseases, including Waardenburg syndromes, oculocutaneous albinism, Tietz syndrome, and piebaldism. APDs are part of the neurocristopathies, a group of congenital multisystem disorders caused by an altered development of the neural crest cells, multipotent progenitors of a wide variety of different lineages, including those differentiating into peripheral nervous system glial cells and melanocytes. We report on clinical and genetic findings of two monozygotic twins from a large Albanian family who showed a complex phenotype featured by sensorineural congenital deafness, severe neuropsychiatric impairment, and inborn pigmentary defects of hair and skin. The genetic analyzes identified, in both probands, an unreported co-occurrence of a new heterozygous germline pathogenic variant (c.2484 + 5G > T splicing mutation) in the KIT gene, consistent with the diagnosis of piebaldism, and a heterozygous deletion at chromosome 15q13.3, responsible for the neuropsychiatric impairment. This case represents the first worldwide report of dual locus inherited syndrome in piebald patients affected by a complex auditory-pigmentary multisystem phenotype. Here we also synthesize the clinical and genetic findings of all known neurocristopathies characterized by a hypopigmentary congenital disorder.

Primary carcinoid tumors of the skin are exceptional, with only ten cases reported from 1975 to date. We describe a case of a 66-year-old woman with a primary cutaneous carcinoid developed on the scalp. The tumor was completely excised and clinical investigations as well as diagnostic studies failed to reveal internal primary site, neither at the time of the excision, neither during follow-up. Nevertheless, 7 years after the surgical excision, she developed a recurrence of the lesion on the same site. To the best of our knowledge, this is the first report of a primary relapsing carcinoid of the skin described up to now. Interestingly, the tumour expresses estroprogestinic receptors.

The authors present a surgical procedure to remove two contiguous cutaneous lesions using a single transposition flap and suture line without an evident scar. This method is useful when rhomboid surgical exeresis could not represent the best choice to obtain an optimum aesthetic result.

A sustainable, reagent-less and one-pot ultrasonic methodology has been developed to transform amorphous tannic acid into regularly shaped crystalline ellagic acid particles. Multiple and consecutive reactions have been performed on tannic acid, in aqueous solution without the addition of any external reagent. The size, morphology and bio-activity of ellagic acid micro-nanocrystals can be finely tuned by choosing appropriate ultrasonic parameters.

An oil-in-water emulsion was ultrasonically prepared in aqueous chitosan solutions containing different counterions. Tetradecane was used as the oil phase in order to mimic nonpolar substances used in food processes. Various acids were used to dissolve chitosan, and we found that conjugate bases of the acids used, which act as counterions to neutralize the positive charges of ammonium ions present in the chitosan backbone, played a significant role in controlling the size, size distribution, and stability of chitosan-encapsulated tedradecane emulsion droplets (microspheres). The counterion effect is also found to be strongly dependent upon tetradecane (TD)/chitosan (CS) ratio and ultrasonic power. Key observations are: (i) for a given TD/CS ratio, the size and size distribution decrease when the acid is varied from nitric acid to benzenesulfonic acid at high TD/CS ratio, and the effect becomes less significant at low TD/CS ratio; (ii) for a given acid, the size and size distribution increase with an increase in TD/CS ratio; and (iii) at low TD/CS ratio the size and size distribution are significantly influenced by the viscosity of the system. A possible mechanism for the observed counterion effect is proposed. The role of counterions, solution viscosity, and ultrasonic power in controlling the physical and functional properties of ultrasonically generated chitosan-stabilized tetradecane microspheres is discussed in detail. The key new finding of this study is that it is possible to form stable emulsions without the addition of external emulsifiers and stabilizers, but only using chitosan with different acids to dissolve chitosan. This strategy could be used in the generation of stable food emulsions.

We present a 21-year-old Italian girl with an 8-year history of missed diagnosed prurigo pigmentosa (PP) successfully treated with short monotherapy with minocycline. PP is an inflammatory disease characterized by recurrent pruritic erythematous papules followed by reticular hyperpigmentation usually located on the trunk. About 300 cases of PP have been described mainly in Japan, whereas only few cases have been reported in Italy. This report shows that minocycline is rapidly effective probably through its ability to scavenge reactive oxygen species and to inhibit the chemotaxis and neutrophil function. Other than its ethnic rarity, this case is very interesting because it is the third case of PP in Caucasian patient with prepubescent onset.

Treatment of scalp defects after tumor resection or traumatic events is a challenging problem. Large defects with loss of soft tissue down to the bone require complex reconstructive options, including tissue expansion, local and distal scalp flaps, and free split thickness skin graft. Nonetheless, these techniques are often disfiguring and are limited by the relatively poor elasticity and vascularity of scalp tissues after recurrent resection or previous irradiation. Moreover, comorbid conditions among elderly patients often limit anesthetic tolerance and the use of distant flaps. We report a case of a 75-year-old woman with large tissue loss and bone exposure after Mohs micrographic surgery of basal cell carcinoma of the scalp which was successfully rebuilt through the use of a skin substitute. We describe the uncommon use of a bilayer matrix wound dressing as a single procedure option for the management of full-thickness scalp defects with bone exposure.

BACKGROUND Recent reports have revealed the therapeutic potential of cell-mediated immunity in neoplasms such as cutaneous squamous cell carcinoma (SCC). OBJECTIVES To define the antigenic coexpression of regulatory T cells (Tregs) and plasmacytoid dendritic cells (pDCs) and assess the CD8(+) /Foxp3(+) CD25(+) cell ratio at peritumoral and intratumoral levels in order to investigate a correlation with the aggressiveness of SCC tumours. METHODS We evaluated the content and distribution of Foxp3(+) CD25(+) Treg and CD123(+) pDC infiltration and assessed CD8(+) /Foxp3(+) CD25(+) cell ratio at peritumoral and intratumoral levels in 40 SCCs (20 well-differentiated, G1; and 20 moderately to poorly differentiated, G2-G3) to investigate a correlation with their aggressiveness. We determined the profiles of Tregs and CD123(+) cells; immunostained for CD4, CD8, CD123, interleukin (IL)-1 and transforming growth factor (TGF)-β1; and unequivocally double stained for Foxp3CD25. RESULTS Peritumorally, CD4, CD8 and Foxp3 expression showed no difference between the two groups. CD123(+) cells were fewer in G2-G3 (P = 0·0005), while Foxp3(+) CD25(+) cells were more numerous (P = 0·0005). The Foxp3(+) CD25(+) /Foxp3(+) ratio was higher in G2-G3 cases (P = 0·0005), confirming the trend in this group of activated T lymphocytes towards total Treg Foxp3(+) cells, while the CD8(+) /Foxp3(+) CD25(+) ratio was higher in G1 (P = 0·0005). Intratumorally, CD4(+) and CD8(+) cells infiltrated G2-G3 (P = 0·048) more than G1 (P = 0·004), whereas almost all cells were CD123 negative. Regarding Foxp3CD25, TGF-β1 and IL-10, they were less expressed in G1, whereas they were positive in G2-G3 (P

Basal cell carcinoma (BCC) is a common skin cancer worldwide. However, BCC of the nipple and areola complex is rare. Men are more affected than women. Most of the cases were treated with simple excision. We report a case of BCC of the right nipple-areola complex in a 75-year-old man, treated with Mohs surgery and simple mastectomy.

Surgical wounds resulting from the excision of cutaneous malignancies or benign neoplasms can be repaired in a number of ways. One alternative, which has been used extensively in our practice, is the purse-string suture. This method offers many advantages respect to the traditional closure. In this cases report we describe four illustrative cases. These cases represent almost all the advantages of the pursestrings suture.

The ultrasonic irradiation of aqueous solution is demonstrated to be a suitable source of initiating radicals for a controlled radical polymerization when conducted in the presence of a thiocarbonylthio-containing reversible addition-fragmentation chain transfer (RAFT) agent. This allows for a highly "green" method of externally regulated/controlled polymerization with a potentially broad scope for polymerizable monomers and/or polymer structures.

Background Endogenous Retroviruses (HERV) are believed to be pathogenic in several autoimmune diseases. Among them, HERV-K viruses have been recently reported to be involved in the pathogenesis of rheumatoid arthritis (RA). Objectives In this study we have explored the role of humoral immune response against HERV-K as a potential pathogenetic mechanism in RA. Methods Four different peptides from the extracellular portion of the env protein of HERV-K (env-su 19–37, env-su 109–26, env-su 164–205, env-su 209–226) were selected by bioinformatic analysis on the basis of their putative immunogenicity. Indirect ELISA was then carried out to quantify antibodies against those peptides on blood samples from RA patients and healthy controls (HC). Differences between the two groups were analysed using the Mann-Whitney rank-sum and chi-square tests. Potential correlations between RA laboratory, clinical descriptors and IgGs levels were explored by bivariate regression analysis. Results Seventy consecutive RA patients and seventy-one HC crossed by age and sex were enrolled in the study. Serum autoantibodies against three out of the four tested peptides, anti HERV-Ksu19–37, HERV-K env-su109–126 and HERV-K env-su205–226, were significantly more prevalent in RA than in HC (19% vs 3%,p=0.0001;9% vs 3%, p=0.0001; and 6% vs 3%, p=0.0001 respectively) (See Fig. 1) Subgroup analysis showed no association between anti-HERV-K peptide humoral response and clinical, serological and clinimetric RA disease descriptors. Conclusions Serum from RA patients in our series significantly reacted against different HERV-K peptides in comparison to the general population suggesting a role for the HERV-K related, secondary antigenic driven immune response in the pathogenesis of RA. Further studies are needed to confirm these results and to explore the role of HERV-K surface peptides as potential therapeutic targets. Disclosure of Interest None declared

Summary Endogenous retroviruses (HERV) are believed to be pathogenic in several autoimmune diseases. Among them, HERV-K viruses have been reported recently to be involved in the pathogenesis of rheumatoid arthritis (RA). In this study we have explored the role of humoral immune response against HERV-K as a potential pathogenetic mechanism in RA. Four different peptides from the extracellular portion of the env protein of HERV-K (env-su19–37, env-su109–126, env-su164–186, env-su209–226) were selected by bioinformatic analysis on the basis of their putative immunogenicity. Indirect enzyme-linked immunosorbent assay (ELISA) was then carried out to quantify antibodies against those peptides on blood samples of 70 consecutive RA patients and 71 healthy controls (HC). Differences between the two groups were analysed using the Mann–Whitney test. Potential correlations between RA laboratory, clinical descriptors and immunoglobulin (Ig)G levels were explored by bivariate regression analysis. Serum autoantibodies against one of four tested peptides of HERV-K (env-su19–37) were significantly higher in RA than in HC (19 versus 3%, P = 0·0025). Subgroup analysis showed no association between anti-HERV-K peptide humoral response and clinical, serological and clinimetric RA disease descriptors. Serum from RA patients in our series reacted significantly against HERV-K env-su19–37 peptide in comparison to the general population suggesting a role for the HERV-K- related, secondary antigenic-driven immune response in the pathogenesis of RA. Further studies are needed to confirm these results and to explore the role of this HERV-K surface peptide as a potential therapeutic target.

Introduction. Mycobacterium marinum is a non-tubercular mycobacterium residing in fresh or salt water (in tropical or temperate areas); it is a fish and human pathogen, and in immunocompromised patients can cause severe cutaneous and subcutaneous infections. Case presentation. A 46-year-old white man who underwent immunosuppressive therapy was admitted to our department in May 2016 for skin lesions previously diagnosed as ‘unusual erysipelas’. We rejected the hypothesis of erysipelas, due to the clinical features, and our diagnostic hypotheses were oriented towards sporotrichosis, atypical mycobacteriosis, cutaneous tuberculosis and cutaneous sarcoidosis. Histological examination performed after a skin biopsy was compatible with a diagnosis of sporotrichosis. However, PCR performed on fresh tissue demonstrated the presence of M. marinum. Conclusion. The case reported is interesting for the unusual clinical localization and modality of infection. The patient became infected by contact with contaminated remains or in the sea, in a geographical area not endemic for M. marinum. The previous state of immunosuppression favoured infection; however, the presence of M. marinum in this area suggests a possible tropicalization of the water of the Mediterranean Sea. To our knowledge, this case is the only one reported in the literature with this modality of infection and in that geographical area.

Cryptococcus neoformans is opportunistic encapsulated yeast that represents the most frequent cryptococcal species found in humans. It can cause three types of infections: pulmonary cryptococcosis, cryptococcal meningitis and cutaneous cryptococcosis. Cutaneous cryptococcosis may represent the dissemination of a systemic infection (especially from nervous or pulmonary primary site of infection) or may be the only localization, due to a direct inoculation into the skin, because of a traumatic injury. Primary cutaneous cryptococcosis (PCC) is rare and mainly affects elderly patients, from rural areas, with history of cutaneous injuries and activities predisposing wounds or exposure to bird droppings. Immunosuppression may be a predisponing factor. The most utilized treatment is fluconazole, but often, especially for ulcers or deep wounds; surgery is required for complete tissues repair. Herein, we present a case of PCC in an immunosuppressed patient, with destroying ulcers involving deep tissues, completely resolved after fluconazole treatment, without surgical intervention.

The aim of this study was to determine whether detection of β-HPV gene products, as defined in epidermodysplasia verruciformis skin cancer, could also be observed in lesions from kidney transplant recipients alongside the viral DNA. A total of 111 samples, corresponding to 79 skin lesions abscised from 17 kidney transplant recipients, have been analyzed. The initial PCR analysis demonstrated that β-HPV-DNA was highly present in our tumor series (85%). Using a combination of antibodies raised against the E4 and L1 proteins of the β-genotypes, we were able to visualize productive infection in 4 out of 19 actinic keratoses, and in the pathological borders of 1 out of 14 squamous cell carcinomas and 1 out of 31 basal cell carcinomas. Increased expression of the cellular proliferation marker minichromosome maintenance protein 7 (MCM7), that extended into the upper epithelial layers, was a common feature of all the E4-positive areas, indicating that cells were driven into the cell cycle in areas of productive viral infections. Although the present study does not directly demonstrate a causal role of these viruses, the detection of E4 and L1 positivity in actinic keratosis and the adjacent pathological epithelium of skin cancer, clearly shows that β-HPV are actively replicating in the intraepidermal precursor lesions of kidney transplant recipients and can therefore cooperate with other carcinogenic agents, such as UVB, favoring skin cancer promotion.