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Objectives. This review aims to understand whether Photobiomodulation (PBM) therapy is a valid aid in the management of Oral Lichen Planus (OLP) and its symptoms. Moreover, an analysis to determine whether it is a valid replacement for conventional therapies and whether standardized protocols can be used in PBM sessions or whether these should be changed depending on the type of injury has been made. Finally, an evaluation to determine whether PBM may induce transformation of dysplastic oral keratinocytes into squamous cell carcinoma has been made. Materials and Methods. Searches were conducted on two search databases for relevant publications released between 1992 and 2019. The databases used were: Pubmed "Medline", and Google Scholar. Forty-four articles complied with the inclusion criteria and were included for quality assessment and data extraction. Results. All the studies reported positive effects of PBM; however, there was wide heterogeneity in the laser parameters used in the management of the OLP. The effective dose ranges from 2 to 3 J/cm2, in order to see the desired biological effects. Conclusions. PBM is useful in controlling algal sensation and can be used in cases of OLP lesions that are not responsive to conventional therapies or when corticosteroid doses are too high for the patient, resulting in possible side effects. Standardized biostimulation protocols with further scientific insights are therefore required. [ABSTRACT FROM AUTHOR]

Background: In hemophilia and von Willebrand disease, the degree of alteration of laboratory assays correlates with bleeding manifestations. Few studies have assessed the predictive value for bleeding of laboratory assays in patients with inherited platelet function disorders (IPFDs)., Objectives: To assess whether there is an association between platelet function assay results and bleeding history, as evaluated by the International Society on Thrombosis and Haemostasis (ISTH) bleeding assessment tool (BAT)., Methods: Centers participating in the international ISTH-BAT validation study were asked to provide results of the diagnostic assays employed for the patients they enrolled, and the association with the individual patients' bleeding score (BS) was assessed., Results: Sixty-eight patients with 14 different IPFDs were included. Maximal amplitude of platelet aggregation was significantly lower in patients with a pathologic BS and correlated inversely with the BS, a finding largely driven by the subgroup of patients with Glanzmann thrombasthenia and CalDAG-GEFI deficiency; after their exclusion, TRAP-induced aggregation remained significantly lower in patients with a pathologic BS. Bleeding time was significantly more prolonged in patients with a high BS than in those with a normal BS (27.1 ± 6.2 minutes vs 15.1 ± 10.6 minutes; P  < .01). Reduced α-granule content was significantly more common among patients with a pathologic BS than among those with a normal BS (80% vs 20%; P  < .05). Receiver operating characteristic curve analysis revealed a significant discriminative ability of all the aforementioned tests for pathologic BS ( P  < .001), also after exclusion of patients with Glanzmann thrombasthenia and CalDAG-GEFI deficiency., Conclusion: This study shows that altered platelet laboratory assay results are associated with an abnormal ISTH-BAT BS in IPFD., (© 2023 The Author(s).)

Introduction: Natalizumab (NTZ), a monoclonal antibody against the integrin α4β1 (VLA-4) found on activated T cells and B cells, blocks the interaction of this integrin with adhesion molecules of central nervous system (CNS) endothelial cells and lymphocyte migration through the blood-brain barrier, effectively preventing new lesion formation and relapses in multiple sclerosis (MS). Whether NTZ treatment has additional effects on the peripheral immune system cells, and how its actions compare with other MS disease-modifying treatments, have not been extensively investigated. In particular, its effect on the proportions of circulating regulatory T cells (Treg) is unclear., Methods: In this study, we investigated the effect of NTZ treatment in 12 patients with relapsing MS, at 6 and 12 months after the start of treatment. We evaluated the proportions of regulatory T cells (Treg), defined by flow cytometry as CD4+ CD25++ FoxP3+ cells and CD4+ CD25++ CD127- cells at these intervals. As an exploratory study, we also investigated the NTZ effects on the proportions of bulk T and B lymphocyte populations, and of those expressing novel the markers CD195 (CCR5), CD196 (CCR6), or CD161 (KLRB1), which are involved in MS pathogenesis but have been studied less in the context of MS treatment. The effects of NTZ were compared to those obtained with 11 patients under interferon-beta-1a (IFN-β1a) treatment, and against 9 healthy volunteers., Results: We observed a transient increment in the proportion of Treg cells at 6 months, which was not sustained at 12 months. We observed a reduction in the proportion of T cells expressing CD195 (CCR5) and CD161 (KLRB1) subsets of T cells., Conclusion: We conclude that NTZ does not have an effect on the proportion of Treg cells over 1 year, but it may affect the expression of molecules important for some aspects MS pathogenesis, in a manner that is not shared with IFN-β1a., (© 2023. The Author(s).)

Background: It is uncertain whether higher doses of anticoagulants than recommended for thromboprophylaxis are necessary in COVID-19 patients hospitalized in general wards METHODS: This is a multicentre, open-label, randomized trial performed in 9 Italian centres, comparing 40 mg b.i.d. versus 40 mg o.d. enoxaparin in COVID-19 patients, between April 30 2020 and April 25 2021. Primary efficacy outcome was in-hospital incidence of venous thromboembolism (VTE): asymptomatic or symptomatic proximal deep vein thrombosis (DVT) diagnosed by serial compression ultrasonography (CUS), and/or symptomatic pulmonary embolism (PE) diagnosed by computed tomography angiography (CTA). Secondary endpoints included each individual component of the primary efficacy outcome and a composite of death, VTE, mechanical ventilation, stroke, myocardial infarction, admission to ICU. Safety outcomes included major bleeding., Results: The study was interrupted prematurely due to slow recruitment. We included 183 (96%) of the 189 enrolled patients in the primary analysis (91 in b.i.d., 92 in o.d.). Primary efficacy outcome occurred in 6 patients (6.5%, 0 DVT, 6 PE) in the o.d. group and 0 in the b.id. group (ARR 6.5, 95% CI: 1.5-11.6). The absence of concomitant DVT and imaging characteristics suggests that most pulmonary artery occlusions were actually caused by local thrombi rather than PE. Statistically nonsignificant differences in secondary and safety endpoints were observed, with two major bleeding events in each arm., Conclusions: No DVT developed in COVID-19 patients hospitalized in general wards, independently of enoxaparin dosing used for thromboprophylaxis. Pulmonary artery occlusions developed only in the o.d. group. Our trial is underpowered and with few events., (© 2021 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Background: Antibodies against cationic platelet chemokine, platelet factor 4 (PF4/CXCL4), have been described in heparin-induced thrombocytopenia (HIT), but also in patients positive for antiphospholipid antibodies (aPL) even in the absence of heparin treatment and HIT-related clinical manifestations. Anti-PF4 antibodies have been recently described also in subjects who developed thrombosis with thrombocytopenia syndrome (TTS) in association with adenoviral vector-based, but not with mRNA-based, COVID-19 vaccines., Objective: To investigate whether COVID-19 vaccination affects the production of anti-PF4 antibodies in aPL-positive patients and in control groups., Methods: Anti-PF4 immunoglobulins were detected in patients' and controls' serum samples by ELISA and their ability to activate normal platelets was assessed by the platelet aggregation test., Results: Anti-PF4 were found in 9 of 126 aPL-positive patients, 4 of 50 patients with COVID-19, 9 of 49 with other infections, and 1 of 50 aPL-negative patients with systemic lupus erythematosus. Clinical manifestations of TTS were not observed in any aPL patient positive for anti-PF4, whose serum failed to cause platelet aggregation. The administration of COVID-19 vaccines did not affect the production of anti-PF4 immunoglobulins or their ability to cause platelet aggregation in 44 aPL-positive patients tested before and after vaccination., Conclusions: Heparin treatment-independent anti-PF4 antibodies can be found in aPL-positive patients and asymptomatic carriers, but their presence, titre as well as in vitro effect on platelet activation are not affected by COVID-19 vaccination., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Optimal management of venous thromboembolism (VTE) in cancer patients with thrombocytopenia is uncertain. We described current management and clinical outcomes of these patients. We retrospectively included a cohort of cancer patients with acute VTE and concomitant mild (platelet count 100,000-150,000/mm 3 ), moderate (50,000-99,000/mm 3 ), or severe thrombocytopenia (< 50,000/mm 3 ). Univariate and multivariate logistic regression analyses explored the association between different therapeutic strategies and thrombocytopenia. The incidence of VTE and bleeding complications was collected at a 3-month follow-up. A total of 194 patients of whom 122 (62.89%) had mild, 51 (26.29%) moderate, and 22 (11.34%) severe thrombocytopenia were involved. At VTE diagnosis, a full therapeutic dose of LMWH was administered in 79.3, 62.8 and 4.6% of patients, respectively. Moderate (OR 0.30; 95% CI 0.12-0.75), severe thrombocytopenia (OR 0.01; 95% CI 0.00-0.08), and the presence of cerebral metastasis (OR 0.06; 95% CI 0.01-0.30) were independently associated with the prescription of subtherapeutic LMWH doses. Symptomatic VTE (OR 4.46; 95% CI 1.85-10.80) and pulmonary embolism (OR 2.76; 95% CI 1.09-6.94) were associated with the prescription of full therapeutic LMWH doses. Three-month incidence of VTE was 3.9% (95% CI 1.3-10.1), 8.5% (95% CI 2.8-21.3), 0% (95% CI 0.0-20.0) in patients with mild, moderate, and severe thrombocytopenia, respectively. The corresponding values for major bleeding and mortality were 1.9% (95% CI 0.3-7.4), 6.4% (95% CI 1.7-18.6), 0% (95% CI 0.0-20.0) and 9.6% (95% CI 5.0-17.4), 48.2% (95% CI 16.1-42.9), 20% (95% CI 6.6-44.3). In the absence of sound evidence, anticoagulation strategy of VTE in cancer patients with thrombocytopenia was tailored on an individual basis, taking into account not only the platelet count but also VTE presentation and the presence of cerebral metastasis., (© 2021. The Author(s).)

Objectives: To evaluate the impact of an educational intervention based on the Italian Society of Internal Medicine Choosing Wisely (CW-SIMI) recommendations., Design: Multicenter, interventional, controlled study., Setting: Twenty-three acute-care hospital wards in Italy., Participants: 303 Physicians working in internal medicine wards., Intervention: An online educational course., Main Outcomes: The rate of proton pump inhibitor (PPI) prescriptions, the number of days of central venous catheter (CVC) usage, and the duration of intravenous (IV) antibiotic prescriptions evaluated at one month (T1) and at six months (T2) after course completion. Patients admitted and discharged during a 30-day period before the educational intervention (T0, one year before T2) were considered the comparison group., Results: A total of 232 physicians completed the course, while 71 did not attend the course. Data from 608, 662, and 555 patients were analyzed at T0, T1, and T2, respectively. The rate of PPI prescriptions declined at one month (RR: 0.67, 95% CI: 0.52-0.87, p = 0.0005) and at six months (RR: 0.62, 95% CI: 0.46-0.84, p = 0.003), and the number of days of CVC usage was reduced at six months (9.13 days at T0 vs. 5.52 days at T2, p = 0.007). The duration of IV antibiotic prescriptions displayed a decreasing trend (7.94 days at T0 vs. 7.42 days at T2, p = 0.081)., Conclusions: A simple online educational intervention based on the CW-SIMI recommendations was associated with a clinically relevant reduction in the usage of PPIs and CVCs. Further studies are needed to confirm these findings and a possible benefit on patients' outcomes., (Copyright © 2021. Published by Elsevier B.V.)

Objectives: This review aims to understand whether Photobio-modulation (PBM) therapy is a valid aid in the management of Oral Lichen Planus (OLP) and its symptoms. Moreover, an analysis to determine whether it is a valid replacement for conventional therapies and whether standardized protocols can be used in PBM sessions or whether these should be changed depending on the type of injury has been made. Finally, an evaluation to determine whether PBM may induce transformation of dysplastic oral keratinocytes into squamous cell carcinoma has been made., Materials and Methods: Searches were conducted on two search databases for relevant publications released between 1992 and 2019. The databases used were: Pubmed "Medline", and Google Scholar. Forty-four articles complied with the inclusion criteria and were included for quality assessment and data extraction., Results: All the studies reported positive effects of PBM; how-ever, there was wide heterogeneity in the laser parameters used in the management of the OLP. The effective dose ranges from 2 to 3 J/cm2, in order to see the desired biological effects., Conclusions: PBM is useful in controlling algal sensation and can be used in cases of OLP lesions that are not responsive to conventional therapies or when corticosteroid doses are too high for the patient, resulting in possible side effects. Standardized biostimulation protocols with further scientific insights are therefore required.