An early revascularization strategy is associated with a survival benefit for diabetic patients in cardiogenic shock after acute myocardial infarction

BACKGROUND: The role of diabetes mellitus (DM) in cardiogenic shock (CS) complicating an acute myocardial infarction (AMI) is not well understood. Previous studies have reported an in-hospital mortality rate for patients with DM and CS of about 60%. OBJECTIVES: This study compares the 1-year mortality rates of patients with DM and those without (NDM) and evaluates early revascularization (ERV) compared with initial medical stabilization (IMS) in patients with DM and CS. Methods: Baseline characteristics, clinical and hemodynamic measures, and management were compared for 90 patients (31%) with DM and 198 with NDM (69%) who were randomized to ERV or IMS in the SHOCK Trial. RESULTS: When compared with NDM, patients with DM were of similar age but had higher rates of prior MI (44.4 vs. 27.8%, p = 0.007) and hypertension (56.2 vs. 42.5%, p = 0.04). The DM group had a lower rate of fibrinolytic therapy (44.4 vs. 60.1%, p = 0.02). In patients randomized to ERV, patients with DM had a higher rate of coronary artery bypass grafting (CABG) (50.0 vs. 30.9%, p = 0.03) despite similar rates of triple-vessel disease. The 1-year mortality rates in both groups were equivalent (58.9%). One-year mortality was not associated with diabetes (hazard ratio [HR] 1.02, 95% CI, 0.73-1.42, p = 0.91). The benefit of an ERV strategy was similar (HR [DM] 0.62; HR [NDM] 0.75, p = 0.58). Even after adjusting for the imbalance in CABG rates, 1-year mortality was not associated with DM. CONCLUSION: Diabetes mellitus is not a predictor of 1-year mortality in CS after AMI. The benefit from an ERV strategy is similar for DM and NDM. The management strategies and influence of DM on mortality in CS deserve further evaluation.     

Drug discrimination in methamphetamine-trained monkeys: effects of monoamine transporter inhibitors

The involvement of brain monoamine systems in the discriminative stimulus effects of methamphetamine (MA) was studied in squirrel monkeys by evaluating the effects of differentially selective monoamine uptake inhibitors alone and in combination. In monkeys discriminating i.m. injections of 0.3 mg/kg MA from saline, methamphetamine (0.01-0.3 mg/kg), and dopamine transporter (DAT) inhibitors, including 1-[2-(bis(4-fluorophenyl)-methoxy)ethyl]-4-(3-phenylpropyl)piperazine (GBR 12909; 1.0-17.8 mg/kg) and its analogs AM2502 (1.0-17.8 mg/kg), AM2506 (1.0-30.0 mg/kg), AM2515 (1.0-17.8 mg/kg), and AM2517 (1.0-5.6 mg/kg), produced dose-related increases in responding on the MA-associated lever and, at the highest doses, full substitution. The time course of MA-like effects was similar for equivalent (3.0 mg/kg) doses of GBR 12909 and its most potent analog, AM2517. Unlike the DAT blockers, the selective 5-hydroxytryptamine (serotonin) uptake inhibitor clomipramine (1.0-10.0 mg/kg) and the selective norepinepherine (NE) uptake inhibitor desipramine (1.0-10 mg/kg) produced responding primarily on the saline lever. The selective NE uptake inhibitor nisoxetine partially substituted at the highest dose tested (10.0 mg/kg). Pretreatment with GBR 12909 or AM2517 enhanced the discriminative stimulus effects of MA, shifting the dose-effect curve leftward. The NE uptake inhibitors desipramine or nisoxetine also enhanced the discriminative stimulus effects of MA, whereas clomipramine only attenuated them. These results support the view that dopaminergic mechanisms play a prominent role in the discriminative stimulus effects of MA in monkeys, whereas involvement of serotonergic and noradrenergic systems may be limited to a modulatory role.     

Therapeutic leukocytapheresis for improvement in respiratory function in a woman with hyperleukocytosis and mantle cell lymphoma with a circulating small lymphocyte phenotype

Mantle cell lymphoma is an aggressive malignant B‐cell disorder that often presents with a leukemic picture. Circulating lymphoma cell morphology may vary from small round mature‐appearing lymphocytes resembling the lymphocytes of chronic lymphocytic leukemia to large prolymphocytoid or blastoid cells. Rare reports of hyperleukocytosis with leukostasis, treated with leukocytapheresis, are described in patients with prolymphocytoid or blastoid morphology. We report an 88 year old woman with mantle cell lymphoma, hyperleukocytosis (WBC > 400 × 10³/µL) with severe respiratory compromise but without interstitial or alveolar infiltrates on radiograph or computerized tomography of the chest. She was afebrile and had no central nervous system signs. Circulating lymphoma cell morphology was predominantly of the small lymphocyte type. A two‐whole‐blood‐volume leukocytapheresis reduced her WBC from 465 to 221 × 10³/µL in 150 min. Her respiratory rate decreased from 28/min to 18/min and her arterial oxygen saturation (SpO₂) rose from 91% to 97% on 6 L/min of oxygen by nasal cannula. Severe breathlessness before the procedure abated completely by the end of the procedure. Respiratory compromise may occur in mantle cell lymphoma with hyperleukocytosis with a mature lymphoma cell phenotype, even without a clear picture of leukostasis. Although the ultimate survival of the patient depends on treatment with chemotherapy, leukocytapheresis for alleviation of symptoms may be warranted and should be considered. Respiratory status and response to leukocytapheresis should be documented with physiological measurements. J. Clin. Apheresis 31:398–402, 2016. © 2015 Wiley Periodicals, Inc.     

Divergent outcomes of gut microbiota alteration upon use of spectrum antibiotics in high sugar diet-induced diabetes in rats

Background: A sugar rich diet induces inflammation and insulin resistance (IR) mainly through gut microbiota alteration. Gut dysbiosis increases lipopolysaccharide (LPS) and reduces propionate and butyrate levels to impair the insulin signalling cascades by different molecular pathways, which progresses into IR. The present study was designed to investigate the effect of spectrum specific antibiotics on the modulation of gut microbiota and its signalling pathways to prevent diet-induced diabetes. Methods: Healthy male Wistar rats were divided into a non-diabetic group with a control diet (CD), a diabetic group with a high sucrose diet (HSD) and two antibiotic fed groups (linezolid and cefdinir; administered by oral gavage) along HSD. Physiological, biochemical, inflammatory and microbiome parameters were examined. Results: Cefdinir administration in HSD rats reduced fasting glucose, serum triglyceride, and cholesterol levels compared to HSD alone. In addition, cefdinir reduced serum LPS by decreasing the population of Gram-negative phyla, that is, Bacteroidetes and Proteobacteria in the fecal content. Furthermore, cefdinir treatment decreased hepatic/ileal/colonic Tlr4, Nlr1, and Nf-κB at the mRNA level. Moreover, cefdinir-treated rats had shown increased fecal butyrate and propionate and reduced acetate levels compared to HSD alone. Cefdinir treatment also induced ileal/colonic Gpr43 and Glut4 at the mRNA level after 12 weeks of administration. Conclusions: Taken together, these data suggest that administration of a Gram-negative spectrum antibiotic, that is, cefdinir, has modulated the gut microbiota, and reduced serum LPS and triglycerides, which prevented the progression of IR and inflammation in HSD rats.

A sugar rich diet induces inflammation and insulin resistance (IR) mainly through gut microbiota alteration.     

Case Report: Cystic Adventitial Disease of the External Iliac Artery with Imaging Features of a Complicating Proximal Dissection

IntroductionCystic adventitial disease (CAD) is a rare cause of claudication. We report a case of CAD involving the external iliac artery, with possible cyst rupture intramurally causing significant long segment stenosis of the external iliac artery.Case reportA 52-year-old female presented with sudden onset (over 1 day) lifestyle-limiting claudication affecting the left calf and thigh. CT angiography of the lower limbs revealed an eccentric low density wall thickening of the left external iliac artery (EIA) producing a 70% stenosis and a cystic lesion just distal to the stenosis.DiscussionA diagnosis of cystic adventitial disease was made and the patient proceeded to iliofemoral bypass.     

Clinical experience with PACS at the University of Pennsylvania

A Picture Archiving and Communication System (PACS) was installed in the Medical Intensive Care Unit of the Hospital of the University of Pennsylvania. For one year, 8 week periods of FILM ONLY usage were alternated with 8 week periods of PACS OR FILM usage. The time interval between obtaining portable chest images and taking image dependent actions decreased when the PACS was used, however, about 40% of the action decisions were made without a radiologist's consultation. Only 5% of action decisions were made without consultation during the FILM ONLY periods. A new clinical study for measuring diagnostic accuracy and efficiency as well as communication patterns is described.