BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

New peptide nucleic acids for biotechnological applications

In the present study was designed and realized a new similar to the PNA. It is a chiral nucleo-γ-peptide, dabPNA, isomer of the aegPNA unit and characterized by a 2,4-diaminobutyric acid (DABA)-based backbone carrying the carboxymethylated nucleobase on its α amino group. Differently from aegPNA monomers, dabPNA presents a shorter backbone (3C between the nitrogen atom and the carbonyl) and an enhanced distance between the nucleobase and the backbone, i.e. 3 atoms (1N+2C) instead of 2C in aegPNAs. Furthermore, in comparison with ornPNA that binds to RNA forming a stable triplex, daba-based PNA has a methylene group less in the backbone. To achieve dabPNA oligomers, the new monomers tL-dab, tD-dab, aL-dab and aD-dab were synthesized in good yield using suitable protected building blocks and characterized by NMR and ESI-MS techniques. Initially, the homothymine oligomers (tL-dab)12 and (tD-dab)6 were synthesized, using a synthetic strategy that ensured the maintenance of chirality during the coupling steps, and tested for hybridization towards natural nucleic acids. No binding evidence with both DNA (dA12) and RNA (A12) was revealed by CD and UV experiments. Furthermore, the insertion of a single tL-dab unit in the middle or at N-terminus of a homothymine aegPNA chain leads to a decreased binding efficiency to the target DNA in comparison to full aegPNA.Since dabPNAs based on L- and D-DABA don’t bind natural nucleic acids, we explored the possibility that complementary nucleopeptides based on D or L-DABA could bind between themselves. This property would be interesting in order to develop novel DABA-based dendrimeric systems, as new materials, and also to realize new diagnostic tools, as for example new molecular beacon probe. To verify this interesting possibility, the monomers aL-dab and aD-dab were oligomerized to the homoadenine hexamers (aL-dab)6 and (aD,L-dab)6. In order to find the correct combination of chirality suitable for obtaining the binding, also the (tD,L-dab)6 oligomer were realized to perform the hybridization studies. From CD and UV experiments, binding evidence was revealed in the case of the complementary oligomers with alternate chirality, (aD,L-dab)6 and (tD,L-dab)6, even if the stability of the complex formed was not so high (Tm 11°C). Furthermore, some interesting properties relative to the self-complementary oligomer (aL−dab-tD−dab)3 emerged from preliminary DLS experiments that evidenced the formation of multimeric aggregates for this system. These results, together with the high serum stability of the DABA-based oligomers, suggest further studies on dabPNAs as new self-recognizing bio-inspired polymers, with the potentiality to develop new nanomaterials or new biotechnological tools in bioengineering and biomedical applications

dabPna: Design, Synthesis, And Dna Binding Studies

In continuing our research efforts for developing new oligodeoxynucleotide (ODN)-like drugs and diagnostics, we designed diaminobutyric peptide nucleic acids (dabPNAs), nucleopeptides characterized by a diaminobutyric-based building block that is an isomer of the aminoethylglycyl PNA (aegPNA) unit and the acyclic modification of the aminoprolyl PNA (ampPNA) monomer. In this work we present the solid phase synthesis of a dabPNA oligomer and of two aegPNAs containing a single dabPNA unit. A study relative to their binding ability towards DNA is also reported even in comparison with the well known aegPNAs

Current technologies for anti-ENA antibody detection: State-of-the-art of diagnostic immunoassays

Background: Autoantibodies against extractable nuclear antigens (ENA) play a pivotal role in the diagnosis and classification of systemic autoimmune rheumatic diseases (SARD). In recent years, newly developed methods have enabled the simultaneous and quantitative detection of multiple anti-ENA reactivities. However, data regarding the comparability of results obtained using different technologies across different platforms are scarce. In this study we compared eight different immunoassays, commonly used in current laboratory practice for detection of anti-ENA antibodies. Methods: Sixty patients suffering from different SARD, 10 inflammatory arthritis patients (disease controls) and 10 healthy blood donors were included in this comparative study. Sera were collected in 15 centers belonging to the Study Group on Autoimmune Diseases of the Italian Society of Clinical Pathology and Laboratory Medicine. We evaluated the analytical sensitivity, specificity and diagnostic accuracy of each method for antibodies to Sm, RNP, Ro60, Ro52, Scl70, CENP-B and Jo1. Cohen's kappa was used to analyze the agreement among methods. Results: Average agreement among methods was 0.82, ranging from substantial (k = 0.72) to almost perfect (k = 0.92). However, while the specificity was very good for all methods, some differences emerged regarding the analytical sensitivity. Conclusions: Diagnostic performance of current technologies for anti-ENA antibody detection showed good comparability. However, as some differences exist among methods, laboratory scientists and clinicians must be aware of the diagnostic accuracy of the testing method in use

Ultrasonography tight control and monitoring in Crohn's disease during different biological therapies: a multicenter study

Background & Aims: Bowel ultrasonography (BUS) is a noninvasive tool for evaluating bowel activity in Crohn's disease (CD) patients. Aim of our multicenter study was to assess whether BUS helps to monitor intestinal activity improvement/resolution following different biological therapies. Methods: Adult CD patients were prospectively enrolled at 16 sites in Italy. Changes in BUS parameters [i.e. bowel wall thickening (BWT), lesion length, echo pattern, blood flow changes and transmural healing (TH: normalization of all BUS parameters)] were analyzed at baseline and after 3, 6 and 12 months of different biological therapies. Results: One hundred eighty-eight out of 201 CD patients were enrolled and analyzed (116 males [62%]; median age 36 years). Fifty-five percent of patients were treated with adalimumab, 16% with infliximab, 13% with vedolizumab and 16% with ustekinumab. TH rates at 12 months were 27.5% with an NNT of 3.6. TH at 12 months after adalimumab was 26.8%, 37% after infliximab, 27.2% after vedolizumab and 20% after ustekinumab. Mean BWT improvement from baseline was statistically significant at 3 and 12 months (P <.0001). Median Harvey-Bradshaw index, C-reactive protein and fecal calprotectin decreased after 12 months from baseline (P <.0001). Logistic regression analysis showed colonic lesion was associated with a higher risk of TH at 3 months and a greater BWT at baseline was associated with a lower risk of TH at 3 months [P =.03 (OR 0.70, 95% CI 0.50-0.97)] and 12 months [P =.01 (OR 0.58, 95% CI 0.38-0.89)]. At 3 months therapy optimization during the study was the only independent factor associated with a higher risk of no ultrasonographic response [P =.02 (OR 3.34, 95% CI 1.18-9.47)] and at 12 months disease duration [P =.02 (OR 3.03, 95% CI 1.15-7.94)]. Conclusions: Data indicate that BUS is useful to monitor biologics-induced bowel activity improvement/resolution in CD

Management of penile cancer patients during the COVID-19 pandemic: An eUROGEN accelerated Delphi consensus study.

OBJECTIVES To develop an international consensus on managing penile cancer patients during the COVID-19 acute waves. A major concern for patients with penile cancer during the coronavirus disease 2019 (COVID-19) pandemic is how the enforced safety measures will affect their disease management. Delays in diagnosis and treatment initiation may have an impact on the extent of the primary lesion as well as the cancer-specific survival because of the development and progression of inguinal lymph node metastases. MATERIALS AND METHODS A review of the COVID-19 literature was conducted in conjunction with analysis of current international guidelines on the management of penile cancer. Results were presented to an international panel of experts on penile cancer and infection control by a virtual accelerated Delphi process using 4 survey rounds. Consensus opinion was defined as an agreement of ≥80%, which was used to reconfigure management pathways for penile cancer. RESULTS Limited evidence is available for delaying penile cancer management. The consensus rate of agreement was 100% that penile cancer pathways should be reconfigured, and measures should be developed to prevent perioperative nosocomial transmission of COVID-19. The panel also reached a consensus on several statements aimed at reconfiguring the management of penile cancer patients during the COVID-19 pandemic. CONCLUSIONS The international consensus panel proposed a framework for the diagnostic and invasive therapeutic procedures for penile cancer within a low-risk environment for COVID-19

Outcomes of COVID-19 in 79 patients with IBD in Italy: an IG-IBD study

COVID-19 has rapidly become a major health emergency worldwide. Patients with IBD are at increased risk of infection, especially when they have active disease and are taking immunosuppressive therapy. The characteristics and outcomes of COVID-19 in patients with IBD remain unclear