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Circulating PD-L1 exosomes in HNC patients' plasma but not soluble PD-L1 levels associate with disease progression. .

BACKGROUND Hereditary angioedema is characterized by recurrent attacks of angioedema of the skin, larynx, and gastrointestinal tract. Bradykinin is the key mediator of symptoms. Icatibant is a selective bradykinin B2 receptor antagonist. METHODS In two double-blind, randomized, multicenter trials, we evaluated the effect of icatibant in patients with hereditary angioedema presenting with cutaneous or abdominal attacks. In the For Angioedema Subcutaneous Treatment (FAST) 1 trial, patients received either icatibant or placebo; in FAST-2, patients received either icatibant or oral tranexamic acid, at a dose of 3 g daily for 2 days. Icatibant was given once, subcutaneously, at a dose of 30 mg. The primary end point was the median time to clinically significant relief of symptoms. RESULTS A total of 56 and 74 patients underwent randomization in the FAST-1 and FAST-2 trials, respectively. The primary end point was reached in 2.5 hours with icatibant versus 4.6 hours with placebo in the FAST-1 trial (P = 0.14) and in 2.0 hours with icatibant versus 12.0 hours with tranexamic acid in the FAST-2 trial (P<0.001). In the FAST-1 study, 3 recipients of icatibant and 13 recipients of placebo needed treatment with rescue medication. The median time to first improvement of symptoms, as assessed by patients and by investigators, was significantly shorter with icatibant in both trials. No icatibant-related serious adverse events were reported. CONCLUSIONS In patients with hereditary angioedema having acute attacks, we found a significant benefit of icatibant as compared with tranexamic acid in one trial and a nonsignificant benefit of icatibant as compared with placebo in the other trial with regard to the primary end point. The early use of rescue medication may have obscured the benefit of icatibant in the placebo trial. (Funded by Jerini; ClinicalTrials.gov numbers, NCT00097695 and NCT00500656.)

Molecular prognostic indicators for oropharyngeal squamous cell carcinoma (OSCC), including HPV-DNA detection, epidermal growth factor receptor (EGFR) and p16 expression, have been suggested in the literature, but none of these are currently used in clinical practice. To compare these predictors, 106 newly diagnosed OSCC for the presence of HPV-DNA and expression of p16 and EGFR were analyzed. The 5-year disease-free survival (DFS) and overall survival (OS) were calculated in relation to these markers and a multivariate Cox analysis was performed. Twentyeight percent of the cases contained oncogenic HPV-DNA and 30% were positive for p16. The p16 expression was highly correlated with the presence of HPV-DNA (p < 0.001). Univariate analysis of the 5-year DFS revealed a significantly better outcome for patients with p16-positive tumors (84% vs. 49%, p 5 0.009). EGFR-negative tumors showed a tendency toward a better prognosis in DFS (74% vs. 47%, p 5 0.084) and OS (70% vs. 45%, p 5 0.100). Remarkable and highly significant was the combination of p16 and EGFR expression status, leading to 5-year DFS of 93% for p161/EGFR2 tumors vs. 39% for p162/EGFR1 tumors (p 5 0.003) and to a 5-year OS of 79% vs. 38%, respectively (p 5 0.010). In multivariate analysis p16 remained a highly significant prognostic marker for DFS (p 5 0.030) showing a 7.5-fold increased risk for relapse in patients with p16-negative tumors. Our data indicate that p16 expression is the most reliable prognostic marker for OSCC and further might be a surrogate marker for HPV-positive OSCC. HPV1/p161 tumors tended to have decreased EGFR expression, but using both immunohistological markers has significant prognostic implications. ' 2007 Wiley-Liss, Inc.

Peri-operative SARS-CoV-2 infection increases postoperative mortality. The aim of this study was to determine the optimal duration of planned delay before surgery in patients who have had SARS-CoV-2 infection. This international, multicentre, prospective cohort study included patients undergoing elective or emergency surgery during October 2020. Surgical patients with pre-operative SARS-CoV-2 infection were compared with those without previous SARS-CoV-2 infection. The primary outcome measure was 30-day postoperative mortality. Logistic regression models were used to calculate adjusted 30-day mortality rates stratified by time from diagnosis of SARS-CoV-2 infection to surgery. Among 140,231 patients (116 countries), 3127 patients (2.2%) had a pre-operative SARS-CoV-2 diagnosis. Adjusted 30-day mortality in patients without SARS-CoV-2 infection was 1.5% (95%CI 1.4-1.5). In patients with a pre-operative SARS-CoV-2 diagnosis, mortality was increased in patients having surgery within 0-2 weeks, 3-4 weeks and 5-6 weeks of the diagnosis (odds ratio (95%CI) 4.1 (3.3-4.8), 3.9 (2.6-5.1) and 3.6 (2.0-5.2), respectively). Surgery performed ≥ 7 weeks after SARS-CoV-2 diagnosis was associated with a similar mortality risk to baseline (odds ratio (95%CI) 1.5 (0.9-2.1)). After a ≥ 7 week delay in undertaking surgery following SARS-CoV-2 infection, patients with ongoing symptoms had a higher mortality than patients whose symptoms had resolved or who had been asymptomatic (6.0% (95%CI 3.2-8.7) vs. 2.4% (95%CI 1.4-3.4) vs. 1.3% (95%CI 0.6-2.0), respectively). Where possible, surgery should be delayed for at least 7 weeks following SARS-CoV-2 infection. Patients with ongoing symptoms ≥ 7 weeks from diagnosis may benefit from further delay.

BackgroundOral diseases rank among the most prevalent non-communicable diseases in modern societies. In Germany, oral epidemiological data show that both dental caries and periodontal diseases are highly prevalent, though significant improvements in oral health has been taking in the population within the last decades, particularly in children. It is, therefore, the aim of the Fifth German Oral Health Study (DMS V) to actualize the data on current oral health status and to gather information on oral health behavior and risk factors. In addition to current oral health monitoring, the study will also permit conclusions about trends in the development of oral health in Germany between 1989 and 2014.Methods/DesignDMS V is a cross-sectional, multi-center, nationwide representative, socio-epidemiological study to investigate the oral health status und behavior of the German resident population in four age cohorts. Study participants are children (12-year-olds), adults (35- to 44-year-olds), young olds (65- to 74-year-olds), and old olds (75- to 100-year-olds) who are drawn from local residents’ registration offices. Social-science investigation parameters concern subjective perceptions and attitudes regarding oral health and nutrition, sense of coherence, and socio-demographic data. Clinical oral parameters are tooth loss, caries and periodontitis, prosthodontic status, further developmental and acquired dental hard tissue and mucosal lesions. To ensure reproducibility, the dental investigators are trained and calibrated by experts and multiple reliability checks are performed throughout the field phase. Statistical analyses are calculated according to a detailed statistical analysis plan.DiscussionThe DMS studies first performed in 1989, 1992 and repeated in 1997 and 2005 are the only cross-sectional oral health studies conducted in Germany on a population-based national representative level. Updated prevalence and trend analyses of key oral diseases are, therefore, of major epidemiological and health services research interest.Trial registrationGerman Health Services Research Data Bank VfD_DMSV_13_002152

Angioedema is an underestimated clinical problem. Many cases are nonallergic reactions, e.g. bradykinin‐induced angioedema caused by genetic defects and angiotensin‐converting enzyme (ACE) inhibitors. This difference is crucial for successful therapy, in particular when complete emergency care is not available. Five important forms of nonallergic angioedema can be distinguished: hereditary (HAE), acquired (AAE), renin‐angiotensin‐aldosterone system (RAAS)‐blocker‐induced (RAE), pseudoallergic angioedema (PAE) and idiopathic angioedema (IAE). Some angioedema are present in the larynx and may cause death. A vast majority of nonallergic angioedema are RAE, particularly those caused by ACE inhibitors. It appears important to emphasize that in patients with complete intolerance to RAAS‐blockers, cessation of RAAS‐blockers is likely to be associated with increased cardiovascular risk. Currently, there is no published algorithm for diagnosis and treatment. Angioedema is usually treated by a conservative clinical approach using artificial ventilation, glucocorticoids and antihistamines. Today, a plasma pool C1‐esterase inhibitor (C1‐INH) concentrate is the therapy of choice in HAE. The current pharmacotherapy of nonallergic angioedema is not satisfactory, thus requiring the identification of effective agents in clinical trials. Recently, several new drugs were developed: a recombinant C1‐INH, a kallikrein inhibitor (ecallantide) and a specific bradykinin‐B2‐receptor antagonist (icatibant). According to currently available reports, these drugs may improve the treatment of kinin‐induced angioedema.