Prognosis of oral epithelial dysplasia in individuals with and without oral lichen planus

OBJECTIVES: To investigate the role of oral lichen planus (OLP) on the long-term prognosis of oral epithelial dysplasia (OED). METHODS: Retrospective single-centre cohort study using the 2007-2019 database of the Head and Neck Cancer and Oral Medicine units of University College London Hospital. The exposure of interest was the presence of OLP and the prognostic outcomes included the development of new primary episodes of OED, progression to malignancy, and mortality. Cox proportional hazard and Poisson regression models were performed. RESULTS: 299 patients, of whom 144 had OED arising on the background of OLP (OLP/OED) and 155 had OED without underlying OLP (non-OLP/OED) were included. A pre-existing diagnosis of OLP was significantly associated with a 2-fold increased risk of subsequent primary OED events (HR=2.02, p=0.04), which also developed faster (1.46 vs 2.96 years, p=0.04) and with more involvement of non-cancer prone sites (p=0.001) than in the non-OLP/OED group. There was no difference between groups in the progression to malignancy or mortality. CONCLUSIONS: OLP/OED patients are at higher risk of multiple episodes of primary OED, which can develop faster and at non-cancer-prone sites as compared to non-OLP/OED individuals. Further research is needed to clarify the effects of OLP upon progression to OSCC and mortality

Biphenotypic sinonasal sarcoma: European multicentre case-series and systematic literature review [Sarcoma bifenotipico nasosinusale: case-series europeo multicentrico e revisione sistematica della letteratura]

Obiettivo: Il sarcoma nasosinusale bifenotipico (SNSB) è un raro tumore a basso grado, incluso a partire dalla 4° edizione WHO dei tumori testa-collo. L’obiettivo di questo studio è analizzare i tassi di sopravvivenza e i pattern di recidiva di questa neoplasia. Metodi: Revisione retrospettiva dei pazienti affetti da SNSB, trattati mediante approccio endoscopico in 6 centri di riferimento europei. È stata condotta inoltre una revisione sistematica della letteratura dal 2012 ad oggi, secondo le linee guida PRISMA. Risultati: . Sono stati inclusi 15 pazienti (approccio endoscopico endonasale in 7 casi, craniectomia endoscopica transnasale in 4 casi, approccio combinato transcranico in 4 casi). In 2 casi è stata somministrata radioterapia adiuvante. Dopo un periodo di follow-up medio di 27,3 mesi, è stato riscontrato un caso di metastasi a distanza; i tassi di 5-year Overall Survival e Disease-Free Survival erano 100% e 80 ± 17,9%, rispettivamente. Conclusioni: . Il SNSB è un tumore localmente aggressivo con un basso tasso di recidiva e tassi di sopravvivenza incoraggianti se trattato con asportazione chirurgica radicale con radioterapia adiuvante per casi selezionati. La chirurgia endoscopica ha dimostrato di essere sicura ed efficace come trattamento iniziale all’interno di un protocollo di cura multidisciplinare.Objective: Biphenotypic sinonasal sarcoma (BSNS) is a rare low-grade cancer that was included from the 4th edition of WHO classification of head and neck tumours. The purpose of this study is to analyse clinical behaviour, pattern of recurrences and survival outcomes of this neoplasm. Methods: Retrospective review of patients affected by BSNS who were treated via an endoscopic-assisted approach in 6 European tertiary-care referral hospitals. Cases of BSNS described in literature since 2012 to date were fully reviewed, according to PRISMA guidelines. Results: A total of 15 patients were included. Seven patients were treated via an endoscopic endonasal approach, 4 with endoscopic transnasal craniectomy, and 4 via a cranio-endoscopic approach. Adjuvant treatment was delivered in 2 cases. After a mean follow-up of 27.3 months, systemic metastasis was observed in 1 case; the 5-year overall survival and disease-free survival rates were 100% and 80 ± 17.9%, respectively. Conclusions: BSNS is a locally aggressive tumour with a low recurrence rate and encouraging survival outcomes if properly treated with surgical resection and free margins followed by adjuvant radiotherapy for selected cases. Endoscopic-assisted surgery is safe and effective as an upfront treatment within a multidisciplinary care protocol

Synthesizing habitat connectivity analyses of a globally important human-dominated tiger-conservation landscape

As ecological data and associated analyses become more widely available, synthesizing results for effective communication with stakeholders is essential. In the case of wildlife corridors, managers in human-dominated landscapes need to identify both the locations of corridors and multiple stakeholders for effective oversight. We synthesized five independent studies of tiger (Panthera tigris) connectivity in central India, a global priority landscape for tiger conservation, to quantify agreement on landscape permeability for tiger movement and potential movement pathways. We used the latter analysis to identify connectivity areas on which studies agreed and stakeholders associated with these areas to determine relevant participants in corridor management. Three or more of the five studies’ resistance layers agreed in 63% of the study area. Areas in which all studies agree on resistance were of primarily low (66%, e.g., forest) and high (24%, e.g., urban) resistance. Agreement was lower in intermediate resistance areas (e.g., agriculture). Despite these differences, the studies largely agreed on areas with high levels of potential movement: >40% of high average (top 20%) current-flow pixels were also in the top 20% of current-flow agreement pixels (measured by low variation), indicating consensus connectivity areas (CCAs) as conservation priorities. Roughly 70% of the CCAs fell within village administrative boundaries, and 100% overlapped forest department management boundaries, suggesting that people live and use forests within these priority areas. Over 16% of total CCAs’ area was within 1 km of linear infrastructure (437 road, 170 railway, 179 transmission line, and 339 canal crossings; 105 mines within 1 km of CCAs). In 2019, 78% of forest land diversions for infrastructure and mining in Madhya Pradesh (which comprises most of the study region) took place in districts with CCAs. Acute competition for land in this landscape with globally important wildlife corridors calls for an effective comanagement strategy involving local communities, forest departments, and infrastructure planners

Outcomes with a shorter multidrug-resistant tuberculosis regimen from Karakalpakstan, Uzbekistan

Background In 2016, WHO guidelines conditionally recommended standardised shorter 9–12 month regimens for multidrug-resistant tuberculosis (MDR-TB) treatment. We conducted a prospective study of a shorter standardised MDR-TB regimen in Karakalpakstan, Uzbekistan. Methods Consecutive adults and children with confirmed rifampicin-resistant pulmonary TB were enrolled between 1st September 2013 and 31st March 2015; exclusions included prior treatment with second-line anti-TB drugs, and documented resistance to ofloxacin or to two second-line injectable agents. The primary outcome was recurrence-free cure at 1 year following treatment completion. Results Of 146 enrolled, 128 patients were included: 67 female (52.3%), median age 30.1 (IQR 23.8–44.4) years. At the end of treatment, 71.9% (92/128) patients achieved treatment success, with 68% (87/128) achieving recurrence-free cure at 1 year following completion. Unsuccessful outcomes during treatment included 22 (17.2%) treatment failure with fluoroquinolone resistance amplification in 8 patients (8/22, 36.4%); 12 (9.4%) loss to follow-up; 2 (1.5%) deaths. Recurrence occurred in one patient. 14 patients (10.9%) experienced serious adverse events. Baseline resistance to both pyrazinamide and ethambutol (aOR 6.13, 95% CI 2.01;18.63) and adherence<95% (aOR 5.33, 95% CI 1.73;16.36) were associated with unsuccessful outcome in multivariable logistic regression. Conclusions Overall success with a standardised shorter MDR-TB regimen was moderate with considerable treatment failure and amplification of fluoroquinolone resistance. When introducing standardised shorter regimens, baseline drug susceptibility testing and minimising missed doses are critical. High rates globally of pyrazinamide, ethambutol and ethionamide resistance raise questions of continued inclusion of these drugs in shorter regimens in the absence of DST-confirmed susceptibility

Frequent HPV-independent p16/INK4A overexpression in head and neck cancer

Objectives p16INK4A (p16) is the most widely used clinical biomarker for Human Papillomavirus (HPV) in head and neck squamous cell cancer (HNSCC). HPV is a favourable prognostic marker in HNSCC and is used for patient stratification. While p16 is a relatively accurate marker for HPV within the oropharynx, recent reports suggest it may be unsuitable for use in other HNSCC subsites, where a smaller proportion of tumors are HPV-driven. Materials and methods We integrated reverse phase protein array (RPPA) data for p16 with HPV status based on detection of viral transcripts by RNA-seq in a set of 210 HNSCCs profiled by The Cancer Genome Atlas project. Samples were queried for alterations in CDKN2A, and other pathway genes to investigate possible drivers of p16 expression. Results While p16 levels as measured by RPPA were significantly different by HPV status, there were multiple HPV (?) samples with similar expression levels of p16 to HPV (+) samples, particularly at non-oropharyngeal subsites. In many cases, p16 overexpression in HPV (?) tumors could not be explained by mutation or amplification of CDKN2A or by RB1 mutation. Instead, we observed enrichment for inactivating mutations in the histone H3 lysine 36 methyltransferase, NSD1 in HPV (?)/p16-high tumors. Conclusions RPPA data suggest high p16 protein expression in many HPV (?) non-oropharyngeal HNSCCs, limiting its potential utility as an HPV biomarker outside of the oropharynx. HPV-independent overexpression of wild-type p16 in non-oropharyngeal HNSCC may be linked to global deregulation of chromatin state by inactivating mutations in NSD1

Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points