Closed-loop oxygen control improves oxygen therapy in acute hypoxemic respiratory failure patients under high flow nasal oxygen: a randomized cross-over study (the HILOOP study).

Background: We aimed to assess the efficacy of a closed-loop oxygen control in critically ill patients with moderate to severe acute hypoxemic respiratory failure (AHRF) treated with high flow nasal oxygen (HFNO).

Methods: In this single-centre, single-blinded, randomized crossover study, adult patients with moderate to severe AHRF who were treated with HFNO (flow rate ≥ 40 L/min with FiO ≥ 0.30) were randomly assigned to start with a 4-h period of closed-loop oxygen control or 4-h period of manual oxygen titration, after which each patient was switched to the alternate therapy.

Early Tracheostomy for Managing ICU Capacity During the COVID-19 Outbreak: A Propensity-Matched Cohort Study.

Background: During the first wave of the COVID-19 pandemic, shortages of ventilators and ICU beds overwhelmed health care systems. Whether early tracheostomy reduces the duration of mechanical ventilation and ICU stay is controversial.

Research Question: Can failure-free day outcomes focused on ICU resources help to decide the optimal timing of tracheostomy in overburdened health care systems during viral epidemics?

Study Design And Methods: This retrospective cohort study included consecutive patients with COVID-19 pneumonia who had undergone tracheostomy in 15 Spanish ICUs during the surge, when ICU occupancy modified clinician criteria to perform tracheostomy in Patients with COVID-19.

Correction to: A Phase II Study Evaluating Combined Neoadjuvant Cetuximab and Chemotherapy Followed by Chemoradiotherapy and Concomitant Cetuximab in Locoregional Oesophageal Cancer Patients.

Errors were subsequently identified in the article and the following corrections should be noted.

A phase II Study Evaluating Combined Neoadjuvant Cetuximab and Chemotherapy Followed by Chemoradiotherapy and Concomitant Cetuximab in Locoregional Oesophageal Cancer Patients.

Background: Pre-operative chemoradiotherapy using a 5-fluorouracil (5-FU)/cisplatin backbone is widely used to improve surgical outcomes in locoregional oesophageal cancer patients, despite a non-negligible failure rate.

Objective: We evaluated intensification of this approach to improve patient outcomes by adding cetuximab to induction 5-FU/cisplatin/docetaxel (TPF) and to chemoradiotherapy in a phase II study.

Patients And Methods: Between November 2006 and April 2009, 50 patients with stage II-IVa squamous cell carcinoma (SCC) or adenocarcinoma of the oesophagus or gastro-oesophageal junction initiated three TPF/cetuximab cycles.

Phase I pharmacokinetic and pharmacodynamic study of the first-in-class spliceosome inhibitor E7107 in patients with advanced solid tumors.

Purpose: To assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical activity of E7107 administered as 5-minute bolus infusions on days 1, 8, and 15 in a 28-day schedule.

Experimental Design: Patients with solid tumors refractory to standard therapies or with no standard treatment available were enrolled. Dose levels of 0.

Pharmacogenomic and pharmacoproteomic studies of cetuximab in metastatic colorectal cancer: biomarker analysis of a phase I dose-escalation study.

Purpose: This study assessed biomarkers for cetuximab efficacy in tissue samples collected during a phase I dose-escalation study exploring every second week administration of cetuximab as first-line therapy in patients with metastatic colorectal cancer (mCRC).

Patients And Methods: Sixty-two patients received cetuximab monotherapy for 6 weeks, followed by cetuximab plus infusional fluorouracil, leucovorin, and irinotecan until disease progression. Patients in the control arm received cetuximab as a 400 mg/m(2) initial dose then 250 mg/m(2) per week; patients in the dose-escalation arms received 400 to 700 mg/m(2) every second week.

Development of new drug strategies in infrequent digestive tumors: esophageal, biliary tract, and anal cancers.

Purpose Of Review: In the last years, interesting advances have been reported in the treatment of infrequent digestive tumors. The increasing development of new targeted therapies in human cancer has also impacted in these rare gastrointestinal malignancies providing a wide range of possibilities in the design of future clinical trials.

Recent Findings: The inhibition of angiogenesis and the blockage of the epidermal growth factor receptor pathway have provided the most interesting activity in recently reported studies for esophageal and biliary tract carcinomas.

Anti-epidermal growth factor receptor monoclonal antibodies in cancer treatment.

Although the prognosis of cancer remains poor recent advances in the diagnostic methods, new approaches in surgical procedures and the development of new therapeutic agents have had a significant impact in the outcome of cancer patients. A better understanding of the molecular pathways that characterize cell growth, apoptosis, angiogenesis and invasion has provided novel targets in cancer therapy. The epidermal growth factor receptor (EGFR) mediated signal transduction has been one of the most studied pathways in carcinogenesis.

Understanding the predictive role of K-ras for epidermal growth factor receptor-targeted therapies in colorectal cancer.

The prognosis of metastatic colorectal cancer (mCRC) remains poor regardless of the advances obtained in recent years with new therapeutic agents, surgical procedures, and diagnostic methods. New treatments directed to molecular targets have emerged and are being developed to improve these results, but there is a need to optimize and define the best use of these new approaches. Current use of irinotecan, oxaliplatin, and bevacizumab combined with the long-time standards 5-fluorouracil and leucovorin as first- or second-line treatment for patients with mCRC has resulted in median overall survival figures of > 20 months.

The role of salvage treatment in advanced colorectal cancer.

The selection of salvage therapy after first-line treatment failure for metastatic colorectal cancer patients has become more complex with the development of several active drugs in this setting. The addition of oxaliplatin and irinotecan to 5-fluorouracil in the first-line therapy has conditioned the election of the regimen used in second-line, becoming a standard of care the switch between both schedules at the time of disease progression. The recent introduction of new targeted drugs has complicated the scenario even more, allowing different possible combinations in first-, second-, third- and even fourth-line therapy.

Update on novel strategies to optimize cetuximab therapy in patients with metastatic colorectal cancer.

The prognosis of metastatic colorectal cancer (mCRC) remains poor despite the advances made in recent years with new therapeutic agents, surgical procedures, and diagnostic methods. New treatments directed toward molecular targets have emerged and are being developed to improve these results, but there is a need to optimize and define the best use of these new approaches. Cetuximab is a chimeric monoclonal antibody that binds to the epidermal growth factor receptor and thereby inhibits cell proliferation, metastasis, and angiogenesis.

Oxaliplatin-based chemotherapy in the management of colorectal cancer.

Oxaliplatin is the only third-generation platinum derivative compound that has found a place in the routine treatment of colorectal cancer (CRC). The appearance of oxaliplatin, as well as irinotecan, in the CRC treatment armamentarium has offered new standards for adjuvant treatment and greater hopes in metastatic disease. Moreover, the combination of oxaliplatin-based chemotherapy with new targeted drugs has improved response rates and survival of these patients.

Aurora kinase family: a new target for anticancer drug.

Aurora kinases (AK) are the name given to a family of Serine/threonine (Ser/Thr) protein kinases. These proteins represent a novel family of kinases crucial for cell cycle control. The cell division process is one of the hallmarks of every living organism.

Dose- and schedule-dependent inhibition of the mammalian target of rapamycin pathway with everolimus: a phase I tumor pharmacodynamic study in patients with advanced solid tumors.

Purpose: Everolimus is a selective mammalian target of rapamycin (mTOR) inhibitor with promising anticancer activity. In order to identify a rationally based dose and schedule for cancer treatment, we have conducted a tumor pharmacodynamic phase I study in patients with advanced solid tumors.

Patients And Methods: Fifty-five patients were treated with everolimus in cohorts of 20, 50, and 70 mg weekly or 5 and 10 mg daily.

New approaches in systemic treatment of advanced colorectal cancer: the molecular targets era.

The prognosis of advanced colorectal cancer remains poor in spite of the advances obtained in recent years with new therapeutic agents, new approaches in surgical procedures and new diagnostic methods. New treatments directed to molecular targets have emerged and are being developed to improve these results, but there is a need to optimize and define the best use of these new approaches. In this review, the authors examine the most important trials with monoclonal antibodies and tyrosine kinase inhibitors in the treatment of advanced colorectal cancer.

Long term results of a phase II trial of induction chemotherapy with uracil-ftegafur (UFT), vinorelbine and cisplatin (UFTVP) followed by radiotherapy concomitant with UFT and carboplatin (RT/UFTJ) in non-resectable locally advanced (stage IV-B) squamous cell head and neck carcinoma and peripheral blood stem cell support (PBSCS) with febrile neutropenia.

Purpose: To evaluate the response of advanced squamous cell head and neck carcinoma to a combination of induction chemotherapy and radiotherapy.

Methods: We present long-term results of a phase II trial of Induction Chemotherapy with UFT 200 mg/m(2) p.o.

Novel targets for anticancer treatment development in colorectal cancer.

Despite recent advances in the treatment of metastatic colorectal cancer (CRC), the prognosis of patients with this malignancy remains poor. An emerging understanding of the molecular pathways that characterize cell growth, cell cycle, apoptosis, angiogenesis, and invasion has provided novel targets in cancer therapy. Numerous proteins have been implicated as having a crucial role in CRC.

[Discomfort and pain during mammography].

Introduction: Mammography is the most important method for early detection of breast cancer, however, patients frequently complain of discomfort and pain.

Objective: Evaluate how often discomfort and pain are felt during mammography and identify factors that may be associated to these complaints.

Methods: A prospective study including 2,164 patients recruited from public (996) and private (1,168) health services was carried out.

T-cell stimulating protein A (TspA) of Neisseria meningitidis is required for optimal adhesion to human cells.

T-cell stimulating protein A (TspA) is an immunogenic, T-cell and B-cell stimulating protein of Neisseria meningitidis. Sequence similarity between TspA and FimV, a Pseudomonas aeruginosa protein involved in twitching motility, suggested a link between TspA and type IV pili (Tfp). To determine the role of TspA an isogenic deletion mutant was created.

Novel targets in gastric and esophageal cancer.

Esophageal cancer (EC) and gastric cancer (GC) constitute a major cause of cancer deaths worldwide. Recent improvements in both surgical techniques and adjuvant/neoadjuvant chemotherapy, radiotherapy or both have increased the survival of patients with loco-regional disease. However, most patients with GC or EC have advanced disease either at diagnosis or during the follow-up, and despite recent advances, these patients still do poorly.

Epidermal growth factor receptor (EGFR) inhibitors in gastrointestinal cancer.

Gastrointestinal (GI) cancer continues to be a leading cause of cancer morbidity and mortality worldwide. Over the past decade the treatment options for patients with GI cancers have increased with the advent of newer combination chemotherapy regimes. Despite these clinical advances, new strategies are warranted in order to improve the efficacy as well as the safety.

Programmed ribosomal frameshifting in HIV-1 and the SARS-CoV.

Ribosomal frameshifting is a mechanism of gene expression used by several RNA viruses to express replicase enzymes. This article focuses on frameshifting in two human pathogens, the retrovirus human immunodeficiency virus type 1 (HIV-1) and the coronavirus responsible for severe acute respiratory syndrome (SARS). The nature of the frameshift signals of HIV-1 and the SARS-CoV will be described and the impact of this knowledge on models of frameshifting will be considered.