The differential diagnosis for failure to wean from mechanical ventilation.

Purpose Of Review: In this review, we discuss the causes for a failed weaning trial and specific diagnostic tests that could be conducted to identify the cause for weaning failure. We briefly highlight treatment strategies that may enhance the chance of weaning success.

Recent Findings: Impaired respiratory mechanics, respiratory muscle dysfunction, cardiac dysfunction, cognitive dysfunction, and metabolic disorders are recognized causes for weaning failure.

Cohort Study on the Management of Cancer-Associated Venous Thromboembolism Aimed at the Safety of Stopping Anticoagulant Therapy in Patients Cured of Cancer.

Background: After diagnosis of cancer-associated VTE, guidelines recommend considering the continuation of anticoagulant treatment until the patient is cured of cancer, although the safety of stopping anticoagulant treatment after the patient is cured has never been evaluated.

Methods: We conducted a cohort study in consecutive patients in whom cancer-associated VTE was diagnosed at the Leiden University Medical Center between January 2001 and January 2010 and monitored for the effect of cancer treatment, occurrence of recurrent VTE, major hemorrhage, and death.

Results: Of the 358 patients with cancer-associated VTE, anticoagulant treatment was continued until the death of 207 patients.

Results of 20- versus 45-min post-infusion scalp cooling time in the prevention of docetaxel-induced alopecia.

Purpose: For patients, chemotherapy-induced alopecia (CIA) is one of the most distressing side effects of treatment. Scalp cooling can prevent or minimise CIA; the results may depend on the duration of cooling. Since a previous study on post-infusion cooling time in patients treated with docetaxel chemotherapy found no difference between 90 and 45 min, we investigated whether hair-preserving results could be maintained with a shorter post-infusion cooling time.

(Secondary) solid tumors in thyroid cancer patients treated with the multi-kinase inhibitor sorafenib may present diagnostic challenges.

Background: Sorafenib is an orally active multikinase tyrosine kinase inhibitor (TKI) that targets B-type Raf kinase (BRAF), vascular endothelial growth factor receptors (VEGFR) 1 and 2, and rearranged during transfection (RET), inducing anti-angiogenic and pro-apoptotic actions in a wide range of solid tumors. A side effect of sorafenib is the occurrence of cutaneous squamous tumors.

Case Presentation: Here we describe three patients with a history of sorafenib treatment for advanced radioactive iodine refractory papillary thyroid cancer (two with a BRAF c.

Insulin-like growth factor 1 receptor expression and IGF1R 3129G > T polymorphism are associated with response to neoadjuvant chemotherapy in breast cancer patients: results from the NEOZOTAC trial (BOOG 2010-01).

Background: The insulin-like growth factor 1 (IGF-1) pathway is involved in cell growth and proliferation and is associated with tumorigenesis and therapy resistance. This study aims to elucidate whether variation in the IGF-1 pathway is predictive for pathologic response in early HER2 negative breast cancer (BC) patients, taking part in the phase III NEOZOTAC trial, randomizing between 6 cycles of neoadjuvant TAC chemotherapy with or without zoledronic acid.

Methods: Formalin-fixed paraffin-embedded tissue samples of pre-chemotherapy biopsies and operation specimens were collected for analysis of IGF-1 receptor (IGF-1R) expression (n = 216) and for analysis of 8 candidate single nucleotide polymorphisms (SNPs) in genes of the IGF-1 pathway (n = 184) using OpenArray® RealTime PCR.

Short-term hyperoxia does not exert immunologic effects during experimental murine and human endotoxemia.

Oxygen therapy to maintain tissue oxygenation is one of the cornerstones of critical care. Therefore, hyperoxia is often encountered in critically ill patients. Epidemiologic studies have demonstrated that hyperoxia may affect outcome, although mechanisms are unclear.

Vitamin D (25-0H D3) status and pathological response to neoadjuvant chemotherapy in stage II/III breast cancer: Data from the NEOZOTAC trial (BOOG 10-01).

Background: Serum levels of 25-OH vitamin D3 (vitamin D) have been shown to be prognostic for disease-free survival in patients with breast cancer. We investigated the predictive value of these levels for pathological response after neoadjuvant chemotherapy in patients with breast cancer taking part in the NEOZOTAC phase-III trial. Additionally, the effect of chemotherapy on vitamin D levels was studied.

Effects of the 34C>T Variant of the AMPD1 Gene on Immune Function, Multi-Organ Dysfunction, and Mortality in Sepsis Patients.

Introduction: Adenosine exerts anti-inflammatory and tissue-protective effects during systemic inflammation. While the tissue-protective effects might limit organ damage, its anti-inflammatory properties may induce immunoparalysis and impede bacterial clearance. The common 34C>T loss-of-function variant of AMPD1 (rs17602729) is associated with increased adenosine formation, but effects on immune function and outcome in sepsis patients are unknown.

The effects of short-term fasting on tolerance to (neo) adjuvant chemotherapy in HER2-negative breast cancer patients: a randomized pilot study.

Background: Preclinical evidence shows that short-term fasting (STF) protects healthy cells against side effects of chemotherapy and makes cancer cells more vulnerable to it. This pilot study examines the feasibility of STF and its effects on tolerance of chemotherapy in a homogeneous patient group with early breast cancer (BC).

Methods: Eligible patients had HER2-negative, stage II/III BC.

Muscle Ultrasound in Patients with Glycogen Storage Disease Types I and III.

In glycogen storage diseases (GSDs), improved longevity has resulted in the need for neuromuscular surveillance. In 12 children and 14 adults with the "hepatic" (GSD-I) and "myopathic" (GSD-III) phenotypes, we cross-sectionally assessed muscle ultrasound density (MUD) and muscle force. Children with both "hepatic" and "myopathic" GSD phenotypes had elevated MUD values (MUD Z-scores: GSD-I > 2.

A phase 1/2 study combining gemcitabine, Pegintron and p53 SLP vaccine in patients with platinum-resistant ovarian cancer.

Purpose: Preclinical tumor models show that chemotherapy has immune modulatory properties which can be exploited in the context of immunotherapy. The purpose of this study was to determine the feasibility and immunogenicity of combinations of such an immunomodulatory chemotherapeutic agent with immunotherapy, p53 synthetic long peptide (SLP) vaccine and Pegintron (IFN-α) in patients with platinum-resistant p53-positive epithelial ovarian cancer (EOC).

Experimental Design: This is a phase 1/2 trial in which patients sequential 6 cycles of gemcitabine (1000 mg/kg2 iv; n = 3), gemcitabine with Pegintron before and after the first gemcitabine cycle (Pegintron 1 μg/kg sc; n = 6), and gemcitabine and Pegintron combined with p53 SLP vaccine (0.

[Ascites drainage at home].

Ascites can lead to many symptoms, and often occurs in patients with an end-stage malignancy such as ovarian, pancreatic, colonic, or gastric cancer. Intermittent ascites drainage is applied in these patients as a palliative measure. As frequent drainage is necessary, a subcutaneously tunnelled permanent ascites catheter is a good alternative for intermittent drainage.

Beneficial Effects of the mTOR Inhibitor Everolimus in Patients with Advanced Medullary Thyroid Carcinoma: Subgroup Results of a Phase II Trial.

Objective. Until recently, advanced medullary thyroid cancer (MTC) had few treatment options except surgery. The mTOR inhibitor everolimus has shown encouraging results in neuroendocrine tumors.

A phase I trial combining carboplatin/doxorubicin with tocilizumab, an anti-IL-6R monoclonal antibody, and interferon-α2b in patients with recurrent epithelial ovarian cancer.

Background: The immune system is important in epithelial ovarian cancer (EOC). Interleukin-6 is associated with chemoresistance and an immune-suppressive tumor microenvironment. We investigated whether a combination of chemotherapeutics, blockade of interleukin 6 (IL-6) receptor (IL-6R; tocilizumab), and immune enhancer interferon-α (Peg-Intron) is feasible, safe, and able to enhance immunity in patients with recurrent EOC.

EFFECTS OF EXPERIMENTAL HUMAN ENDOTOXEMIA ON DIAPHRAGM FUNCTION.

Introduction: Systemic inflammation is a well-known risk factor for respiratory muscle weakness. Studies using animal models of inflammation have shown that endotoxin administration induces diaphragm dysfunction. However, the effects of in vivo endotoxin administration on diaphragm function in humans have not been studied.

The Involvement of Danger-Associated Molecular Patterns in the Development of Immunoparalysis in Cardiac Arrest Patients.

Objectives: After cardiac arrest, patients are highly vulnerable toward infections, possibly due to a suppressed state of the immune system called "immunoparalysis." We investigated if immunoparalysis develops following cardiac arrest and whether the release of danger-associated molecular patterns could be involved.

Design: Observational study.

Development of a Standardized Set of Patient-centered Outcomes for Advanced Prostate Cancer: An International Effort for a Unified Approach.

Background: There are no universally monitored outcomes relevant to men with advanced prostate cancer, making it challenging to compare health outcomes between populations.

Objective: We sought to develop a standard set of outcomes relevant to men with advanced prostate cancer to follow during routine clinical care.

Design, Setting, And Participants: The International Consortium for Health Outcomes Measurement assembled a multidisciplinary working group to develop the set.

Validity and Predictive Value of a Portable Two-Channel Sleep-Screening Tool in the Identification of Sleep Apnea in Patients With Heart Failure.

Background: Sleep apnea is an important comorbidity in heart failure (HF) and is associated with an adverse outcome. Diagnosing sleep apnea is difficult, and polysomnography, considered to be the criterion standard, is not widely available. We assessed the validity of a portable 2-channel sleep-screening tool for the identification of sleep apnea in patients with HF.

Crew Resource Management in the Intensive Care Unit: a prospective 3-year cohort study.

Background: Human factors account for the majority of adverse events in both aviation and medicine. Human factors awareness training entitled "Crew Resource Management (CRM)" is associated with improved aviation safety. We determined whether implementation of CRM impacts outcome in critically ill patients.

Transvenous vagus nerve stimulation does not modulate the innate immune response during experimental human endotoxemia: a randomized controlled study.

Introduction: Vagus nerve stimulation (VNS) exerts beneficial anti-inflammatory effects in various animal models of inflammation, including collagen-induced arthritis, and is implicated in representing a novel therapy for rheumatoid arthritis. However, evidence of anti-inflammatory effects of VNS in humans is very scarce. Transvenous VNS (tVNS) is a newly developed and less invasive method to stimulate the vagus nerve.

Nurses' worry or concern and early recognition of deteriorating patients on general wards in acute care hospitals: a systematic review.

Introduction: Nurses often recognize deterioration in patients through intuition rather than through routine measurement of vital signs. Adding the 'worry or concern' sign to the Rapid Response System provides opportunities for nurses to act upon their intuitive feelings. Identifying what triggers nurses to be worried or concerned might help to put intuition into words, and potentially empower nurses to act upon their intuitive feelings and obtain medical assistance in an early stage of deterioration.

Interleukin-6 receptor and its ligand interleukin-6 are opposite markers for survival and infiltration with mature myeloid cells in ovarian cancer.

An increased level of interleukin-6 (IL-6) in epithelial ovarian cancer (EOC) is correlated with a worse prognosis. IL-6 stimulates tumor-growth and inflammation. We investigated the intricate interaction between the IL-6 signaling pathway and tumor-infiltrating myeloid cells (TIMs) to determine their prognostic impact in EOC.