SAUL, a single-arm study of atezolizumab for chemotherapy-pretreated locally advanced or metastatic carcinoma of the urinary tract: outcomes by key baseline factors, PD-L1 expression and prior platinum therapy

Background The impact of pretreatment factors on immune checkpoint inhibition in platinum-refractory advanced urothelial cancer (aUC) deserves further evaluation. The aim was to study the association of Bellmunt risk factors, time from last chemotherapy (TFLC), previous therapy and PD-L1 expression with atezolizumab efficacy in platinum-refractory aUC. Patients and methods This was a post-hoc analysis of patients who had received prior cisplatin or carboplatin in the prospective, single-arm, phase IIIb SAUL study (NCT02928406). Patients were treated with 3-weekly atezolizumab 1200 mg intravenously. The primary outcome was overall survival (OS). Relationships were analysed using Cox regression and long-rank test. Results Of 997 patients in SAUL, 969 were eligible for this analysis. The number of Bellmunt risk factors was associated with OS (P 6 months, 7.75 versus 11.6 months for PD-L1 expression on <1% of tumour-infiltrating immune cells (ICs) (IC0)/expression on 1% to <5% of tumour-infiltrating ICs (IC1) versus expression on ≥5% of tumour-infiltrating ICs (IC2/3) and 10.2 versus 7.8 months for prior versus no prior perioperative chemotherapy, respectively. The type of platinum compound and number of previous treatment lines were not associated with outcomes. Conclusions Post-platinum atezolizumab is active in aUC, irrespective of previous platinum compound and lines of therapy. Bellmunt risk stratification, PD-L1 expression, TFLC and perioperative chemotherapy were identified as prognostic factors for OS with second-line atezolizumab, indicating the need for novel prognostic signatures for immunotherapy-treated patients with aUC

New prognostic model in patients with advanced urothelial carcinoma treated with second-line immune checkpoint inhibitors

Background: Bellmunt Risk Score, based on Eastern Cooperative Oncology Group (ECOG) performance status (PS), hemoglobin levels and presence of liver metastases, is the most established prognostic algorithm for patients with advanced urothelial cancer (aUC) progressing after platinum-based chemotherapy. Nevertheless, existing algorithms may not be sufficient following the introduction of immunotherapy. Our aim was to develop an improved prognostic model in patients receiving second-line atezolizumab for aUC. Methods: Patients with aUC progressing after cisplatin/carboplatin-based chemotherapy and enrolled in the prospective, single-arm, phase IIIb SAUL study were included in this analysis. Patients were treated with 3-weekly atezolizumab 1200 mg intravenously. The development and internal validation of a prognostic model for overall survival (OS) was performed using Cox regression analyses, bootstrapping methods and calibration. Results: In 936 patients, ECOG PS, alkaline phosphatase, hemoglobin, neutrophil-to-lymphocyte ratio, liver metastases, bone metastases and time from last chemotherapy were identified as independent prognostic factors. In a 4-tier model, median OS for patients with 0–1, 2, 3–4 and 5–7 risk factors was 18.6, 10.4, 4.8 and 2.1 months, respectively. Compared with Bellmunt Risk Score, this model provided enhanced prognostic separation, with a c-index of 0.725 vs 0.685 and increment in c-statistic of 0.04 (p<0.001). Inclusion of PD-L1 expression did not improve the model. Conclusions: We developed and internally validated a prognostic model for patients with aUC receiving postplatinum immunotherapy. This model represents an improvement over the Bellmunt algorithm and could aid selection of patients with aUC for second-line immunotherapy. Trial registration number: NCT02928406

Pityriasis rubra pilaris presenting with an abnormal autoimmune profile: Two case reports

Introduction. Pityriasis rubra pilaris is an uncommon inflammatory and hyperproliferative dermatosis of juvenile or adult onset. The etiology of the disease is still unknown. Case presentation. We present the cases of two Caucasian men aged 53 and 48 who presented with pityriasis rubra pillaris type 1; both patients also exhibited an abnormal immunological profile. Conclusion. Pityriasis rubra pillaris is currently classified as a keratinization disorder. The abnormal immunological profile reported in our patients along with the comorbidity of pityriasis rubra pilaris with autoimmune disorders reported in the literature poses the question of a possible pathogenetic role for the immune response in this disorder. © 2009 Gregoriou et al; licensee BioMed Central Ltd

Giant tumour of the heel: Acquired fibrokeratoma

Fibrokeratoma is a rare benign invasive tumour usually located on the digits. We report a 35-year-old patient with a giant acquired fibrokeratoma of the heel. Despite its large size and unusual location, the tumour was microscopically benign and was successfully excised. © 2009 British Association of Dermatologists

Increased prevalence of Chlamydophila pneumoniae but not Epstein-Barr antibodies in essential hypertensives

Conflicting data exist regarding the relationship between Chlamydophila pneunoniae (C. pneumoniae) and hypertension. In this study, both C. pneumoniae IgG and IgA titres and Epstein-Barr virus antibody levels were measured in 146 sustained hypertensives defined by 24 h ambulatory blood pressure monitoring (ABPM) and 54 normotensives. C. pneumoniae antibodies were measured by microimmunofluorescence test. IgG greater than or equal to 80 and IgA greater than or equal to 40 were defined as elevated antibody titres. Epstein-Barr antibodies were measured in order to investigate whether a possible association exists between hypertension and other, similarly widespread in the general population, intracellular microorganisms. All participants underwent casual blood pressure (BP) readings and 24 h ABPM. Subjects having mean 24 h systolic/diastolic ambulatory BP &gt; 125/80 mmHg, with or without anti hypertensive medication were defined as hypertensives. Controls were free of any history or clinical evidence of hypertension, cardiovascular or pulmonary disease. Of the total participants, 77 hypertensives (52.7%) and 10 normotensives (18.5%) had IgA titres greater than or equal to 40 (crosstabs P &lt; 0.000), whereas 76 hypertensives (52.1%) and 15 normotensives (27.8%) had IgG titres greater than or equal to 80, (crosstabs P &lt; 0.002). No difference was found in Epstein-Barr antibodies, between hypertensives and normotensives. In conclusion, C. pneumoniae, but not Epstein-Barr, antibody levels were found significantly higher in sustained hypertensives, suggesting high frequency of chronic C. pneumoniae, infections in this specific group of patients

Analgesic efficacy of an ibuprofenreleasing foam dressing compared with local best practice for painful exuding wounds

Objective: To examine if wound aetiology has an effect on the pain-relieving properties of an ibuprofen-releasing foam dressing, which was previously shown to reduce pain inwounds of various aetiologies, compared with local best practice (LBP). Method: This was a secondary analysis of data from a multicentre, randomised, parallel group trial of patients with painful exuding wounds of various aetiologies. Wound aetiology was determinedatenrolment. Of 853 patients enrolled into the trial, 688 belonged to a wound aetiology subgroup that included &amp;gt; 25 patients and were included in the analysis reported here. Patients were randomised to a dressing containing 112.5mg of ibuprofen (ibuprofen foam) or to LBP for 5 days. Patients recorded pain relief and pain intensity daily. The main endpoint was the proportion of patients who, from day 1 to day 5, reported a summed pain reliefscore &amp;gt; 50% of the total maximum pain relief score (TOTPARD5&amp;gt;50%) and the corresponding number needed to treat (NNT) for each wound aetiology subgroup. Further analyses included the proportion of patients who, on a daily basis, reported pain relief &amp;gt; 50% of the maximum daily pain relief, the proportion of patients who, on day 5,experienced a reduction in pain intensity of &amp;gt; 50% of the maximum score (PIDD5&amp;gt;50%), and if PIDD5&amp;gt;50% was related to baseline pain intensity. Results: Patients were categorised by thefollowing five wound types: arterial, venous, and mixed arterial-venous leg ulcers, vasculitis and traumatic ulcers. The ibuprofenfoam dressing was associated with significantlygreater pain relief than LBP in all different wound aetiology subgroups, whether chronic or traumatic (acute). Overall, TOTPAR D5&amp;gt;50% was 55% in the ibuprofen foam group and 24% in the LBP group (p &amp;lt; 0.0001; NNT, 3.2). The pain intensity evaluations revealed similar results in favour ofibuprofen foam compared with LBP. No correlation was observed between PIDD5&amp;gt;50 and initial pain intensity. Conclusion: In this study, the ibuprofenfoam dressing was shown to consistently relievewound painin exuding wounds of various aetiologies, irrespective of basal painintensity.The data suggest that local pain reliefby an ibuprofenfoam dressing is possible in themost common, painful, exuding, chronic and acute/traumatic wounds and so is a safer alternative to systemic pain treatment. Conflict of interest: Of the ten authors involved inthe preparation of this manuscript, seven declare that theyhave no conflicts of interest. One is a member of the Wound AdvisoryForum for Coloplast A/S, Denmark. Two are employees of Coloplast A/S, Denmark

Hepatitis E virus infection in individuals at high risk of transmission of non-A, non-B hepatitis and sexually transmitted diseases

The aim of the study was to determine the prevalence of hepatitis E virus (HEV) infection among individuals at high risk of transmission of non-A, non-B hepatitis or sexually transmitted diseases (STDs), and to evaluate whether they have an increased risk of exposure to HEV. Serum samples from 125 thalassemia patients, 300 intravenous drug users, 420 hemodialysis patients, 263 individuals with STDs, 47 human immunodeficiency virus (HIV) infected homosexual men, and 316 healthy volunteers were tested for immunoglobulin G (IgG) and M (IgM) antibodies to HEV (anti-HEV) by enzyme immunoassays (EIAs) following a predetermined algorithm (Abbott Labs). Anti-HEV IgG was confirmed in 3/125 (2.4%) thalassemia patients, 5/300 (1.7%) intravenous drug users, 27/420 (6.4%) hemodialysis patients, 4/263 (1.5%) STD patients, 1/47 (2.1%) homosexual men, and 7/316 (2.2%) of the reference group, No patient was found positive for anti-HEV IgM. The higher prevalence which was observed in hemodialysis group was due to the confounding effect of age, as multivariate analysis showed. The anti-HEV prevalence increased significantly with age (p=10(-4)). No significant association was found between anti-HEV, anti-HCV, and anti-HBc. In conclusion, individuals at high risk of non-A, non-B hepatitis and STDs have no increased risk of exposure to HEV and the higher prevalence of anti-KEV Ige among older subjects may be due to an epidemic form of HEV infection which occurred some decades ago, when the sanitary conditions in our country mere poor

Η ενσυναίσθηση σε προπτυχιακούς και μεταπτυχιακούς φοιτητές Λογοθεραπείας. [Abstract]

16ο Πανελλήνιο Συνέδριο Ψυχολογικής Έρευνας, 10-14 Μαΐου, 2017