Does Management of Diabetic Ketoacidosis with Subcutaneous Rapid-acting Insulin Reduce the Need for Intensive Care Unit Admission?

BACKGROUND: In the last 20 years, rapid-acting insulin analogs have emerged on the market, including aspart and lispro, which may be efficacious in the management of diabetic ketoacidosis (DKA) when administered by non-intravenous (i.v.) routes. CLINICAL QUESTION: In patients with mild-to-moderate DKA without another reason for intensive care unit (ICU) admission, is the administration of a subcutaneous (s.c.) rapid-acting insulin analog a safe and effective alternative to a continuous infusion of i.v. regular insulin, and would such a strategy eliminate the need for ICU admission? EVIDENCE REVIEW: Five randomized controlled trials were identified and critically appraised. RESULTS: The outcomes suggest that there is no difference in the duration of therapy required to resolve DKA with either strategy. CONCLUSION: Current evidence supports DKA management with s.c. rapid-acting insulin analogs in a non-ICU setting in carefully selected patients.

The Use of Physostigmine by Toxicologists in Anticholinergic Toxicity.

The anticholinergic toxidrome is well described and relatively common. Despite controversy, studies have shown that physostigmine is relatively safe and effective in reversing this toxidrome. We would expect toxicologists would be liberal in its use. We retrospectively analyzed data in the Toxicology Investigators Consortium (ToxIC) registry, representing data from medical toxicologists in multiple institutions nationwide, searching for patients who exhibited an anticholinergic toxidrome, determining what treatment(s) they received, and classifying the treatments as physostigmine, benzodiazepines, physostigmine and benzodiazepines, antipsychotics, or no definitive treatment. The causal agents of the toxidrome were as reported by the treating toxicologist. Eight hundred fifteen consecutive patients with anticholinergic toxidromes were analyzed. Benzodiazepines alone were given in 28.7 %, 12.4 % were given physostigmine alone, 8.8 % received both physostigmine and benzodiazepines, 2.7 % were given antipsychotics, and 47.4 % were given no definitive treatment. In patients who received only physostigmine, there was a significant difference in the rate of intubation (1.9 vs. 8.4 %, OR 0.21, 95 % CI 0.05-0.87) versus other treatment groups. Physostigmine was given at varying rates based on causative agent with use in agents with mixed or unknown effects (15.1 %) being significantly lower than those with primarily anticholinergic effects (26.6 %) (p < 0.001). Patients with anticholinergic toxicity were more likely to receive benzodiazepines than physostigmine. Those patients who received only physostigmine had a significantly lower rate of intubation. Physostigmine was more likely to be used with agents exerting primarily anticholinergic toxicity than in those agents with multiple actions.

A life-span extending form of autophagy employs the vacuole-vacuole fusion machinery.

While autophagy is believed to be beneficial for life-span extension, it is controversial which forms or aspects of autophagy are responsible for this effect. We addressed this topic by analyzing the life span of yeast autophagy mutants under caloric restriction, a longevity manipulation. Surprisingly, we discovered that the majority of proteins involved in macroautophagy and several forms of microautophagy were dispensable for life-span extension. The only autophagy protein that is critical for life-span extension was Atg15, a lipase that is located in the endoplasmic reticulum (ER) and transported to vacuoles for disintegrating membranes of autophagic bodies. We further found that vacuole-vacuole fusion was required for life-span extension, which was indicated by the shortened life span of mutants missing proteins (ypt7Delta, nyv1Delta, vac8Delta) or lipids (erg6Delta) involved in fusion. Since a known function of vacuole-vacuole fusion is the maintenance of the vacuole membrane integrity, we analyzed aged vacuoles and discovered that aged cells had altered vacuolar morphology and accumulated autophagic bodies, suggesting that certain forms of autophagy do contribute to longevity. Like aged cells, erg6Delta accumulated autophagic bodies, which is likely caused by a defect in lipase instead of proteases due to the existence of multiple vacuolar proteases. Since macroautophagy is not blocked by erg6Delta, we propose that a new form of autophagy transports Atg15 via the fusion of vacuoles with vesicles derived from ER, and we designate this putative form of autophagy as secretophagy. Pending future biochemical studies, the concept of secretophagy may provide a mechanism for autophagy in life-span extension.