Citations

Brown fat is specialized for energy expenditure and has therefore been proposed to function as a defense against obesity. Despite recent advances in delineating the transcriptional regulation of brown adipocyte differentiation, cellular lineage specification and developmental cues specifying brown-fat cell fate remain poorly understood. In this study, we identify and isolate a subpopulation of adipogenic progenitors (Sca-1 + /CD45 − /Mac1 − ; referred to as Sca-1 + progenitor cells, ScaPCs) residing in murine brown fat, white fat, and skeletal muscle. ScaPCs derived from different tissues possess unique molecular expression signatures and adipogenic capacities. Importantly, although the ScaPCs from interscapular brown adipose tissue (BAT) are constitutively committed brown-fat progenitors, Sca-1 + cells from skeletal muscle and subcutaneous white fat are highly inducible to differentiate into brown-like adipocytes upon stimulation with bone morphogenetic protein 7 (BMP7). Consistent with these findings, human preadipocytes isolated from subcutaneous white fat also exhibit the greatest inducible capacity to become brown adipocytes compared with cells isolated from mesenteric or omental white fat. When muscle-resident ScaPCs are re-engrafted into skeletal muscle of syngeneic mice, BMP7-treated ScaPCs efficiently develop into adipose tissue with brown fat-specific characteristics. Importantly, ScaPCs from obesity-resistant mice exhibit markedly higher thermogenic capacity compared with cells isolated from obesity-prone mice. These data establish the molecular characteristics of tissue-resident adipose progenitors and demonstrate a dynamic interplay between these progenitors and inductive signals that act in concert to specify brown adipocyte development.

Background Difficult intubation management algorithms have proven efficacy in operating rooms but have rarely been assessed in a prehospital emergency setting. We undertook a prospective evaluation of a simple prehospital difficult intubation algorithm. Methods All of our prehospital emergency physicians and nurse anesthetists were asked to adhere to a simple algorithm in all cases of impossible laryngoscope-assisted tracheal intubation. They received a short refresher course and training in the use of the gum elastic bougie (GEB) and the intubating laryngeal mask airway (ILMA), which were techniques to be used as a first and a second step, respectively. In cases of difficult ventilation with arterial desaturation, IMLA was to be used first. Cricothyroidotomy was the ultimate rescue technique when ventilation through ILMA failed. Patient characteristics, adherence to the algorithm, management efficacy, and early complications were recorded (August 2005-December 2009). Results An alternative technique to secure the airway was needed in 160 of 2,674 (6%) patients undergoing intubation. Three instances of nonadherence to the algorithm were recorded. GEB was used first in 152 patients and was successful in 115. ILMA was used first in 8 patients and second in the 37 GEB-assisted intubation failures. Forty-five patients were successfully mask-ventilated, and 42 were blindly intubated before reaching the hospital. Cricothyroidotomy was used successfully in a patient with severe upper airway obstruction as a result of pharyngeal neoplasia. Early intubation-related complications occurred in 52% difficult cases. Conclusion Adherence to a simple algorithm using GEB, ILMA, and cricothyroidotomy solved all difficult intubation cases occurring in a prehospital emergency setting.

Background: Historical outcomes in anaplastic thyroid carcinoma (ATC) are poor, with a median survival of only 5 months and <20% of patients surviving 1 year from diagnosis. We hypothesized that survival in newly diagnosed patients with stages IVA and IVB locoregionally confined ATC might be improved by utilizing an aggressive therapeutic approach, prioritizing both the eradication of disease in the neck and preemptive treatment of occult metastatic disease. Methods: Between January 1, 2003, and December 31, 2007, 25 new ATC patients were evaluated at our institution. Of these 25 patients, 10 (40%) had metastatic disease at diagnosis and therefore underwent palliative treatment, whereas 5 (20%) had regionally confined disease and desired treatment at their local medical facilities. The remaining 10 consecutive patients (40%) had regionally confined ATC and elected aggressive therapy combining individualized surgery (where feasible), intensity-modulated radiation therapy (IMRT), and radiosensitizing + adjuvant chemotherapy intending four cycles of docetaxel + doxorubicin. Outcomes were assessed on an intention to treat basis. Results: There were no deaths from therapy, but hospitalization was required in two patients (20%) because of treatment-related adverse events. Five patients (50%) are alive and cancer-free, all having been followed >32 months (range: 32–89 months; median: 44 months) with a median overall Kaplan–Meier survival of 60 months. Overall survival at 1 and 2 years was 70% and 60%, respectively, compared to <20% historical survival at 1 year in analogous patients previously treated with surgery and conventional postoperative radiation at our and other institutions. Conclusions: Although based upon a small series of consecutively treated patients, an aggressive approach combining IMRT and radiosensitizing plus adjuvant chemotherapy appears to improve outcomes, including survival in stages IVA and IVB regionally confined ATC, but remains of uncertain benefit in patients with stage IVC (metastatic) disease. Also uncertain is the optimal chemotherapy regimen to use in conjunction with IMRT. Further multicenter randomized trials are required to define optimal therapy in this rare but deadly cancer.