BackgroundCirculatory shock is a common syndrome with a high mortality and limited therapeutic options. Despite its discovery and use in clinical and experimental settings more than a half-century ago, angiotensin II (Ang II) has only been recently evaluated as a vasopressor in distributive shock. We examined existing literature for associations between Ang II and the resolution of circulatory shock.MethodsWe searched PubMed, MEDLINE, Ovid, and Embase to identify all English literature accounts of intravenous Ang II in humans for the treatment of shock (systolic blood pressure [SBP] ≤ 90 mmHg or a mean arterial pressure [MAP] ≤ 65 mmHg), and hand-searched the references of extracted papers for further studies meeting inclusion criteria. Of 3743 articles identified, 24 studies including 353 patients met inclusion criteria. Complete data existed for 276 patients. Extracted data included study type, publication year, demographics, type of shock, dosing of Ang II or other vasoactive medications, and changes in BP, lactate, and urine output. BP effects were grouped according to type of shock, with additional analyses completed for patients with absent blood pressure. Shock was distributive (n = 225), cardiogenic (n = 38), or from other causes (n = 90). Blood pressure as absent in 18 patients.ResultsFor the 276 patients with complete data, MAP rose by 23.4% from 63.3 mmHg to 78.1 mmHg in response to Ang II (dose range: 15 ng/kg/min to 60 mcg/min). SBP rose by 125.2% from 56.9 mmHg to 128.2 mmHg (dose range: 0.2 mcg/min to a 1500 mcg bolus). A total of 271 patients with complete data were determined to exhibit a BP effect which was directly associated with Ang II. Subgroups (patients with cardiogenic, septic, and other types of shock) exhibited similar increases in BP. In patients with absent BP, deemed to be cardiac arrest, return of spontaneous circulation (ROSC) was achieved, and BP increased by an average of 107.3 mmHg in 11 of 18 patients. The remaining seven patients with cardiac arrest did not respond.ConclusionsIntravenous Ang II is associated with increased BP in patients with cardiogenic, distributive, and unclassified shock. A role may exist for Ang II in restoring circulation in cardiac arrest.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-017-1896-6) contains supplementary material, which is available to authorized users.

Despite great advances in our understanding of the pathobiology of colorectal cancer and the genetic and environmental factors that mitigate its onset and progression, a paucity of effective treatments persists. The five-year survival for advanced, stage IV disease remains substantially less than 20%. This review examines a relatively untapped reservoir of potential therapies to target muscarinic receptor expression, activation, and signaling in colorectal cancer. Most colorectal cancers overexpress M3 muscarinic receptors (M3R), and both in vitro and in vivo studies have shown that activating these receptors stimulates cellular programs that result in colon cancer growth, survival, and spread. In vivo studies using mouse models of intestinal neoplasia have shown that using either genetic or pharmacological approaches to block M3R expression and activation, respectively, attenuates the development and progression of colon cancer. Moreover, both in vitro and in vivo studies have shown that blocking the activity of matrix metalloproteinases (MMPs) that are induced selectively by M3R activation, i.e., MMP1 and MMP7, also impedes colon cancer growth and progression. Nonetheless, the widespread expression of muscarinic receptors and MMPs and their importance for many cellular functions raises important concerns about off-target effects and the safety of employing similar strategies in humans. As we highlight in this review, highly selective approaches can overcome these obstacles and permit clinicians to exploit the reliance of colon cancer cells on muscarinic receptors and their downstream signal transduction pathways for therapeutic purposes.

ObjectiveAlcohol is a hypnotic that modifies immune function, specifically the cytokines interferon gamma (IFN-γ) and interleukin 2 (IL-2). We evaluated the association between unscheduled napping and acute alcohol-induced augmentation of IFN-γ and IL-2 expression.MethodsIn this prospective, observational pilot study, volunteers completed questionnaires on sleep quality, alcohol use, and hangover characteristics. Actigraph recordings began three nights before and continued for four nights after study initiation. Napping was recorded by actigraphy and self-reporting. A weight-based dose of 100-proof vodka was consumed, and the blood alcohol content (BAC) and phytohemagglutinin-M stimulated cytokine level were measured before and 20 minutes, 2 hours, and 5 hours after binge consumption.ResultsTen healthy volunteers participated (mean age, 34.4 ± 2.3 years; mean body mass index, 23.9 ± 4.6 kg/m2; 60% female). The mean 20-minute BAC was 137.7 ± 40.7 mg/dL. Seven participants took an unscheduled nap. The ex vivo IFN-γ and IL-2 levels significantly increased at all time points after binge consumption in the nappers, but not in the non-nappers.ConclusionAugmented IFN-γ and IL-2 levels are associated with unscheduled napping after binge alcohol consumption. Further studies are needed to clarify the associations among alcohol consumption, sleep disruption, and inflammatory mediators.

IntroductionIn the United States, cocaine is a commonly used drug of abuse. It is also a recognized contributing factor for both hemorrhagic and ischemic strokes. However, cocaine-induced basilar artery thrombosis has rarely been reported in the literature.Case presentationOur patient was a 51-year-old African American woman with a history of polysubstance abuse who presented to the emergency department for acute behavior changes. Later, during admission, she had a dramatic decrease in motor strength in all extremities and a positive Babinski reflex bilaterally. The results of her toxicology reports were positive for cocaine; in addition, results of magnetic resonance angiography and magnetic resonance imaging were consistent with acute thrombosis and subsequent infarction of the basilar artery. Her mental status improved, but she was only able to communicate via movements of her eyes.ConclusionOur patient developed locked-in syndrome after use of cocaine. Given the prevalence of its use in the United States, cocaine use should be included among the potential causes of locked-in syndrome.

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An unusual presentation of acute tonsillitis complicated by retropharyngeal and thyroid abscess is reported. Spontaneous rupture of retropharyngeal abscess resulted in necrotic fistulae between the pharyngeal wall and the retropharyngeal space.

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<b><i>Background and Aims:</i></b> Benign esophageal strictures often present with dysphagia and can significantly impair a patient’s quality of life, especially when refractory to standard endoscopic techniques. When repeat dilations fail to achieve an adequate luminal diameter or resolve dysphagia, further therapy with needle-knife or steroid injections is needed. However, patients can still clinically fail. To manage such strictures, we employed a novel combination of all three techniques. <b><i>Methods:</i></b> Single-center case series of adult patients with benign strictures that were refractory to conventional endoscopic therapy and removable self-expanding metal stenting. Primary clinical success was defined as complete resolution in dysphagia. Secondary outcomes included periodic dilation index (frequency of dilations over the follow-up time), esophageal diameter changes, technical success, and complications. <b><i>Results:</i></b> Four patients (median age 49.7 years old, interquartile range [IQR] 30–59) underwent endoscopic therapy for complex, benign strictures using our triple therapy technique. Etiologies of the strictures included peptic strictures (<i>n</i> = 3) and an anastomotic stricture (<i>n</i> = 1). There was 100% technical success rate with no associated adverse events. There was a 50% clinical success rate, with 1 additional patient having partial improvement in dysphagia. The median diameter of the esophagus before and after triple therapy was 3.2 mm (IQR 3.5–5.5) and 12.8 mm (IQR 11.7–14.2), respectively. The periodic dilation index was 6.3 before and 1.5 after triple therapy. The median length of follow-up was 362.5 days. <b><i>Conclusion:</i></b> Triple combination therapy may be useful in benign strictures that are refractory to standard techniques. Larger studies are needed to validate these findings.