Is galectin‐3 a good method for the detection of malignancy in patients with thyroid nodules and a cytologic diagnosis of “follicular neoplasm”? A critical appraisal of the evidence

BACKGROUND: Thyroid nodules are the most common surgical disease of the thyroid. Fine-needle aspiration biopsy (FNAB) is the most commonly employed tool for establishing a diagnosis. However, 15% to 25% of FNAB reports yield inconclusive results. Immunostaining of cytological smears from FNAB with galectin-3 has been proposed as a tool for differentiating between benign and malignant nodules. We performed a systematic review to evaluate the utility of galectin-3. METHODS: Prospective studies of nodules with FNAB reports of "follicular neoplasm" and with a definitive diagnosis confirmed by histopathology were selected. Calculations of individual sensitivity, specificity, and positive and negative likelihood ratios were made. RESULTS: The articles selected were those with the best methodological quality. CONCLUSION: Galectin-3 could be a good tool to guide therapeutic decision in patients with thyroid nodules and FNAB results of follicular neoplasm, but available information has methodological flaws that precludes a definitive answer about galectin-3 utility in the clinical setting.     

Humoral and cellular immune responses to airway immunization of mice with human papillomavirus type 16 virus-like particles and mucosal adjuvants

Cervical cancer results from cervical infection by human papillomaviruses (HPV), especially HPV16. Intramuscular administrations of HPV16 virus-like particle (VLP) vaccines have been shown to induce strong neutralizing antibody responses and protect women against genital HPV16 infection and associated lesions. However, an alternative route of administration that avoids parenteral injection might facilitate vaccine implementation, particularly in developing countries which account for the majority of the worldwide cases of cervical cancer. In addition, inducing mucosal immunity could partially overcome the substantial variation in HPV16 antibodies at the cervix seen in ovulating women. Aerosol vaccination with HPV16 VLPs was previously shown to be immunogenic in mice and in women. Here, we examine whether exposure to other respiratory viral antigens may interfere with the HPV16 VLP-specific humoral response and whether two known mucosal adjuvants, CpG oligodeoxynucleotides and a natural non-toxic Escherichia coli heat-labile enterotoxin (HLT), can enhance the immunogenicity of airway immunization (nasal or aerosol-like) of mice with HPV16 VLPs. Our data show that HLT can significantly improve anti-VLP humoral responses in serum and mucosal secretions, as well as VLP-specific proliferative responses and IFN-gamma production by CD8 T cells, and that recent exposure to influenza surface antigens can diminish mucosal, but not systemic, antibody responses to the VLPs.     

Carnosic acid from rosemary extracts: a potential chemoprotective agent against aflatoxin B1. An in vitro study

Since oxidative stress plays an important role in the toxicity mechanism of several mycotoxins such as aflatoxin B1 (AFB1), the use of natural or synthetic free radical scavengers could be a potential chemopreventive strategy. Carnosic acid (CA) is the major polyphenolic compound present in rosemary plants and it can also be found in sage leaves. Its free radical scavenging properties were tested with two chemical methods. It was found that it has good free radical scavenging capacity at pH 7.4. This study also found that a 24 h pre-treatment with 10, 20 and 30 microm CA led to a clear, dose-dependent protective effect on cell toxicity, reducing cell death induced by a 24 h exposure with 10 microm AFB1, respectively, by 16% (P < 0.05), 26% (P < 0.01) and 63% (P < 0.001). It was also found that a 24 h pre-treatment with 20 and 30 microm CA achieved a reduction of ROS levels, respectively, of 146% (P < 0.001) and 173% (P < 0.001) in HepG2 cells exposed to 10 microm AFB1 for 8 h. Moreover, in cells pre-incubated with 30 microm CA for 24 h the concentration of 8-OH-deoxyguanine decreased by 57% (P < 0.001) with respect to the cells exposed for 24 h to 10 microm AFB1 alone. The results obtained with the in vitro and chemical studies support the theory that AFB1 induced oxidative stress plays an important role in the cytotoxic mechanism of this mycotoxin. Furthermore these findings suggest a starting point for developing alimentary strategies in order to counteract the damage caused by AFB1 contamination in feed and food.     

Conservative treatment of chyle fistula of the neck following a reintervention of cervical bilateral lymphectomy for medullary carcinoma of the thyroid. Case report

Chyle fistula is an uncommon serious complication of neck surgery, occurring in 1-3% of radical neck dissections. An untreated chyle leak is a potentially dangerous condition that may rarely lead to hypovolemia, hyponatremia, hypochloremia, hypoproteinemia and lymphopenia. Anatomic variants of the terminal portion of the thoracic duct and suction drainage in the neck wound play a primary role in causing this kind of lesion. Poor is the literature concerning chyle fistula, due to its rarity, and mostly case reports; still debated--prevalently empiric--is the management of this disease. The Authors report a case of chyle fistula following a reintervention of cervical bilateral lymphectomy for medullary carcinoma of the thyroid in a 75 years old female. In the reported case the chyle fistula was successfully treated conservatively, in early post-operative period with a low-fat diet and total parenteral nutrition, definitely followed by sclerosant therapy. The injection of a sclerosant agent (4 g of sterile medical talc diluted in isotonic sodium chloride solution) into the supraclavicular wound bed, through the drainage tube (clamped for 2 hours), determined rapid decline in fistula output, hence obviating surgical intervention.     

An assessment of the accuracy of renal blood flow estimation by Doppler ultrasound

BACKGROUND: Knowledge of renal blood flow is considered important in the management of critically ill patients with acute renal failure. Renal Doppler ultrasound has been used to estimate renal blood flow. Its accuracy, however, has not been formally assessed. DESIGN: Prospective blinded animal study. SETTING: University physiology laboratory. SUBJECTS: Seven merino cross-ewes. INTERVENTIONS: We chronically implanted transit-time flow probes around the left renal artery and performed Doppler ultrasound measurements of RBF. We simultaneously recorded RBF values obtained with implanted flow probes and Doppler ultrasound during (a) observation, (b) dobutamine and (c) nitroprusside infusion in random order. RESULTS: In a total of 202 paired measurements, Doppler ultrasound measured peak systolic velocity (PSV) correlated very weakly with implanted flow probe measurements of RBF (r (2)[Symbol: see text]=[Symbol: see text]0.015), as did end-diastolic velocity (EDV; r (2)[Symbol: see text]=[Symbol: see text]0.086) and mean velocity (MV_vel; r (2)[Symbol: see text]=[Symbol: see text]0.04). We also found similar weak correlations with other Doppler-ultrasound-derived indices. All comparisons showed bias and wide limits of agreement. CONCLUSIONS: Doppler-ultrasound-derived estimates of RBF show little correlation with transit-time flow probe measurements, display significant bias and wide limits of agreement and have low accuracy for clinically significant changes in RBF in large animals.     

A prospective study of factors influencing the outcome of patients after a Medical Emergency Team review

Objective  To identify factors that predict outcome in patients receiving a Medical Emergency Team review. Design  Prospective observational study. Setting  Tertiary hospital. Patients  Cohort of 228 patients receiving one or more Medical Emergency Team reviews during daytime hours over a 1-year-period. Control cohort of all patients (n = 900) receiving a Medical Emergency Team review in the same period. Measurements and results  We prospectively collected information from patients receiving a Medical Emergency Team review during daytime hours from Monday to Friday (audit group) including the clinical cause of deterioration and timing of call in relation to the first documented Medical Emergency Team call criterion (activation delay). We also collected information from the hospital Medical Emergency Team database regarding all patients visited by the Medical Emergency Team during the same period (complete cohort). Audit group patients had several similar characteristics to complete cohort patients but were less likely to be not-for-resuscitation before Medical Emergency Team review and more likely to receive a Medical Emergency Team review because of hypotension, change in neurological status and oliguria. Delayed Medical Emergency Team activation and not-for resuscitation orders were the only factors to show an independent statistical association with mortality (OR 2.53, 95% CI: 1.2–5.31, P = 0.01 and OR 5.63, 95% CI: 2.81–11.28, P < 0.01, respectively). Conclusion  Delayed Medical Emergency Team activation and NFR orders are the strongest independent predictors of mortality in patients receiving a Medical Emergency Team review. Avoidance of delayed Medical Emergency Team activation should be a priority for hospitals operating rapid response systems.     

Bench-to-bedside review: The evaluation of complex interventions in critical care

Complex interventions, such as the introduction of medical emergency teams or an early goal-directed therapy protocol, are developed from a number of components that may act both independently and inter-dependently. There is an emerging body of literature advocating the use of integrated complex interventions to optimise the treatment of critically ill patients. As with any other treatment, complex interventions should undergo careful evaluation prior to widespread introduction into clinical practice. During the development of an international collaboration of researchers investigating protocol-based approaches to the resuscitation of patients with severe sepsis, we examined the specific issues related to the evaluation of complex interventions. This review outlines some of these issues. The issues specific to trials of complex interventions that require particular attention include determining an appropriate study population and defining current treatments and outcomes in that population, defining the study intervention and the treatment to be used in the control group, and deploying the intervention in a standardised manner. The context in which the research takes place, including existing staffing levels and existing protocols and procedures, is crucial. We also discuss specific details of trial execution, in particular randomization, blinded outcome adjudication and analysis of the results, which are key to avoiding bias in the design and interpretation of such trials. These aspects of study design impact upon the evaluation of complex interventions in critical care. Clinicians should also consider these specific issues when implementing new complex interventions into their practice.