Phase I study of CC-90010, a reversible, oral BET inhibitor in patients with advanced solid tumors and relapsed/refractory non-Hodgkin's lymphoma.

BACKGROUND: Bromodomain and extra-terminal (BET) proteins are epigenetic readers that regulate expression of genes involved in oncogenesis. CC-90010 is a novel, oral, reversible, small-molecule BET inhibitor. PATIENTS AND METHODS: CC-90010-ST-001 (NCT03220347; 2015-004371-79) is a phase I dose-escalation and expansion study of CC-90010 in patients with advanced or unresectable solid tumors and relapsed/refractory (R/R) non-Hodgkin's lymphoma (NHL). We report results from the dose escalation phase, which explored 11 dose levels and four dosing schedules, two weekly (2 days on/5 days off; 3 days on/4 days off), one biweekly (3 days on/11 days off), and one monthly (4 days on/24 days off). The primary objectives were to determine the safety, maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) and schedule. Secondary objectives were to evaluate signals of early antitumor activity, pharmacokinetics, and pharmacodynamics. RESULTS: This study enrolled 69 patients, 67 with solid tumors and two with diffuse large B-cell lymphoma (DLBCL). The median age was 57 years (range, 21-80) and the median number of prior regimens was four (range, 1-9). Treatment-related adverse events (TRAEs) were mostly mild and manageable; grade 3/4 TRAEs reported in more than two patients were thrombocytopenia (13%), anemia, and fatigue (4% each). Six patients had dose-limiting toxicities. MTDs were 15 mg (2 days on/5 days off), 30 mg (3 days on/11 days off), and 45 mg (4 days on/24 days off). The RP2D and schedule selected for expansion was 45 mg (4 days on/24 days off). As of 8 October 2019, one patient with grade 2 astrocytoma achieved a complete response, one patient with endometrial carcinoma had a partial response, and six patients had prolonged stable disease ≥11 months. CONCLUSIONS: CC-90010 is well tolerated, with single-agent activity in patients with heavily pretreated, advanced solid tumors.

Prevalence of M. tuberculosis infection and tuberculosis disease among HIV-infected people in Spain.

OBJECTIVE: To study the prevalence of Mycobacterium tuberculosis infection (MTBI) and past/current tuberculosis (TB) among human immunodeficiency virus (HIV) infected persons in Spain. DESIGN: Longitudinal study conducted between 2000 and 2003 at 10 HIV hospital-based clinics. Data were drawn from clinical records. Associations were measured using odds ratios (ORs) and their 95% confidence intervals (95%CI). RESULTS: Of the 1242 persons who met the eligibility criteria, most were male (75%), aged <40 years (75%) and unemployed (40%). HIV infection occurred through intravenous drug use (53%), heterosexual sex (29%) and sex between men (16%). In the initial evaluation, 315 subjects had evidence of MTBI: 84 (6.8%) had a history of TB, 23 (1.8%) current TB and 208 (16.8%) latent tuberculosis infection (LTBI). MTBI was associated with male sex, age 30-49 years, contact with a TB case, homelessness, poor education, and negatively with CD4 <100 cells/mm(3). Among subjects with MTBI, past/current TB was associated with retirement/disability (OR 6, 95%CI 1.6-22.5), CD4 <200 cells/mm(3) (OR 9.7, 95%CI 3.8-24.6), viral load >55,000 copies (OR 5.3, 95%CI 1.4-20.0), and negatively, with skilled work (OR 0.4, 95%CI 0.1-1.0) or administrative/managerial/professional work (OR 0.05, 95%CI 0.01-0.4). CONCLUSION: Social context has an impact on the effectiveness of HIV and TB control programmes even in industrialised countries with free access to health care.

[Antiseptic agents: chlorhexidine]. / Antisépticos. Clorhexidina.

Chlorhexidine is a broad spectrum antiseptic widely used in clinical practice. This antiseptic works rapidly and its effects last for six hours. Since it is not absorbed through the skin nor through mucus, its systematic toxicity is minimum. It keeps on working in contact with organic matter and, since it is transparent, it does not hide the evolution of injuries. In this article, the authors review the properties and indications for this antiseptic; they also comment on some studies having lesser known indications.

[Antiseptics]. / Antisépticos.

Antiseptics are chemical products which are applied on live tissues in order to eliminate microorganisms potentially pathogenic, or to inhibit their growth. The selection of the antiseptic must be done according to the properties and the recommended uses of the product. This article describes the main antiseptics used in the clinical practice, paying attention to its range of activity, recommended uses and toxicity.

[Innovations and new techniques: tracheostomy cannulas]. / Innovaciones y técnicas nuevas. Cánulas de traqueostomía.

In recent years, therapy by means of a tracheostomy has increased considerably due to the use of new trachea opening procedures and the development of the newest generation of tubes employed in tracheostomy. Percutaneous tracheostomy has become the preferred choice technique for patients in critical condition since it is a simple procedure, almost bloodless, and furthermore, this procedure can be carried out on a patient in a bed in a normal ward. The translaryngeal tracheostomy is one of the newest innovative techniques performed from inside the trachea; due to its complex nature, it is not commonly used yet although it promises to be an alternative procedure when confronting various counter-indications found in the percutaneous technique. In addition to the development of these techniques, substantial design modifications in the tubes used in tracheostomy have been produced; their objectives include improving a patient's comfortableness, reducing complications and easing a nurse's work.

[Care levels in an intensive care unit. Analysis of therapeutic requirements and severity scales]. / Niveles asistenciales en un Servicio de Medicina Intensiva. Análisis de escalas de esfuerzo terapéutico y nivel de gravedad.

The APACHE II and TISS scales usually are used in intensive medicine services to assess patient's severity and therapeutic requirements, respectively. Both scales serve to classify ICU patient's into three care levels, each of which has its own well-defined surveillance and care requirements. Nursing personnel have used the TISS scale to determine work loads and plan nurse-patient ratios. However, this scale is complex and its application is time-consuming, thus impeding its routine use. In recent years, the NEMS (Nine Equivalents of Nursing Manpower) scale has been validated for this purpose. This scale uses just nine variables to objectively quantify nursing requirements. In order to determine if the NEMS scale could be used to evaluate the severity and nursing requirements of patient's admitted to our ICU and to establish care levels, we designed a descriptive study of a sample of 78 patients. The results showed that the APACHE II, TISS and NEMS scales has a good correlation and that the NEMS scale could be used to determine patient care requirements in our service. Based on the TISS and NEMS correlation, we determined discriminative numerical NEMS values for assigning patient's to different care levels.

Synthesis of 3-furylmethylpenicillin using an enzymatic procedure.

3-Furylmethylpenicillin was synthesized in vitro from 3-furylacetic acid, 6-aminopenicillanic acid (6-APA), CoA, ATP and Mg2+. The reaction was catalyzed in two steps by the enzymes phenyl-acetyl-CoA ligase (PCL) from Pseudomonas putida and acyl-CoA: 6-APA acyltransferase (AT) from Penicillium chrysogenum. PCL catalyzes the activation of 3-furylacetic acid to 3-furylacetyl-CoA (3-F-CoA) and AT acylates the amino group of 6-APA with the 3-furylacetyl moiety of 3-F-CoA, releasing CoA and 3-furylmethylpenicillin.