Patterns of nuclear staining included diffuse fine speckles, large coarse speckles, nucleolar and centromere staining. When organ sections such as mouse kidney were used as substrate for the detection of antinuclear antibodies, nucleolar staining and centromere staining were the two patterns most frequently overlooked. Three types of antibodies appeared to be highly specific for scleroderma: antibody to Scl-70 antigen, antibody to centromere, and antinucleolar antibody. The anti-centromere antibody appeared to be highly selective for the CREST variant of progressive systemic sclerosis.

resistant prostate cancer; CTCAE v4.0, Common Terminology Criteria for Adverse Events version 4.0; ECG, electrocardiogram; ECOG, Eastern Cooperative Oncology Group; ER + BC, estrogen receptorpositive breast cancer; FPKM, fragments per kilobase per million reads; FTIH, first time in human; GIST, gastrointestinal stromal tumor; GSEA, gene set enrichment analysis; HIV, human immunodeficiency virus; MSigDB, molecular signatures database; NC, nuclear protein in testis carcinoma; NUT, nuclear protein in testis; ORR, overall response rate; PD, progressive disease; PK, pharmacokinetic; PR, partial response; PSA, prostate-specific antigen; QTcF, QT interval assessment corrected for heart rate by Fridericia's formula; RECIST v1.1, Response Evaluation Criteria In Solid Tumors version 1.1 criteria; RP2D, recommended Phase 2 dose; SAE, serious adverse event; SCLC, small cell lung cancer; SD, stable disease; TNBC, triple-negative breast cancer; ULN, upper limit of normal.Antara Datta was working at GSK at the time of study design and initiation.

Oral squamous cell carcinoma (OSCC) is a very aggressive cancer, representing one of the most common malignancies worldwide. Oral potentially malignant disorders (OPMDs) regroup a variegate set of different histological lesions, characterized by the potential capacity to transform in OSCC. Most of the risk factors associated with OSCC are present also in OPMDs’ development; however, the molecular mechanisms and steps of malignant transformation are still unknown. Treatment of OSCC, including surgery, systemic therapy and radiotherapy (alone or in combination), has suffered a dramatic change in last years, especially with the introduction of immunotherapy. However, most cases are diagnosed during the advanced stage of the disease, decreasing drastically the survival rate of the patients. Hence, early diagnosis of premalignant conditions (OPMDs) is a priority in oral cancer, as well as a massive education about risk factors, the understanding of mechanisms involved in malignant progression and the development of specific and more efficient therapies. The aim of this article is to review epidemiological, clinical, morphological and molecular features of OPMDs, with the purpose to lay the foundation for an exhaustive comprehension of these lesions and their ability of malignant transformation and for the development of more effective and personalized treatments.

Background:We sought to develop and externally validate a nomogram and web-based calculator to individually predict the development of serious complications in seemingly stable adult patients with solid tumours and episodes of febrile neutropenia (FN).Patients and methods:The data from the FINITE study (n=1133) and University of Salamanca Hospital (USH) FN registry (n=296) were used to develop and validate this tool. The main eligibility criterion was the presence of apparent clinical stability, defined as events without acute organ dysfunction, abnormal vital signs, or major infections. Discriminatory ability was measured as the concordance index and stratification into risk groups.Results:The rate of infection-related complications in the FINITE and USH series was 13.4% and 18.6%, respectively. The nomogram used the following covariates: Eastern Cooperative Group (ECOG) Performance Status ⩾2, chronic obstructive pulmonary disease, chronic cardiovascular disease, mucositis of grade ⩾2 (National Cancer Institute Common Toxicity Criteria), monocytes <200/mm3, and stress-induced hyperglycaemia. The nomogram predictions appeared to be well calibrated in both data sets (Hosmer–Lemeshow test, P>0.1). The concordance index was 0.855 and 0.831 in each series. Risk group stratification revealed a significant distinction in the proportion of complications. With a ⩾116-point cutoff, the nomogram yielded the following prognostic indices in the USH registry validation series: 66% sensitivity, 83% specificity, 3.88 positive likelihood ratio, 48% positive predictive value, and 91% negative predictive value.Conclusions:We have developed and externally validated a nomogram and web calculator to predict serious complications that can potentially impact decision-making in patients with seemingly stable FN.