Goal Directed Therapy is the optimization of intraoperative fluids using dynamic markers of volume status such as stroke volume and cardiac output, rather than less sensitive measures such as urine output, blood pressure, and pulse. Using the Frank Starling curve to optimize perfusion with volume, GDT has been shown to decrease complications, decrease hospital and ICU length-of-stay, and decrease overall cost in high-risk patients undergoing surgery. It is not currently in use at UCSD but the aims of this project were to help implement it through resident education.

Few oral health databases are available for research and the advancement of evidence-based dentistry. In this work we developed a centralized data repository derived from electronic health records (EHRs) at four dental schools participating in the Consorti

We previously reported that processed EEG underestimated the amount of burst suppression compared to off-line visual analysis. We performed a follow-up study to evaluate the reasons for the discordance. Forty-five patients were monitored intraoperatively with processed EEG. A computer algorithm was used to convert the SedLine® (machine)-generated burst suppression ratio into a raw duration of burst suppression. The reference standard was a precise off-line measurement by two neurologists. We measured other potential variables that may affect machine accuracy such as age, surgery position, and EEG artifacts. Overall, the median duration of bust suppression for all study subjects was 15.4 min (Inter-quartile Range [IQR] = 1.0-20.1) for the machine vs. 16.1 min (IQR = 0.3-19.7) for the neurologists assessment; the 95% limits of agreement fall within - 4.86 to 5.04 s for individual 30-s epochs. EEG artifacts did not affect the concordance between the two methods. For patients in prone surgical position, the machine estimates had significantly lower overall sensitivity (0.86 vs. 0.97; p = 0.038) and significantly wider limits of agreement ([- 4.24, 3.82] seconds vs. [- 1.36, 1.13] seconds, p = 0.001) than patients in supine position. Machine readings for younger patients (age < 65 years) had higher sensitivity (0.96 vs 0.92; p = 0.021) and specificity (0.99 vs 0.88; p = 0.007) for older patients. The duration of burst suppression estimated by the machine generally had good agreement compared with neurologists estimation using a more precise off-line measurement. Factors that affected the concordance included patient age and position during surgery, but not EEG artifacts.

Background and objectives

Obesity is a global epidemic which increases the risk of the metabolic syndrome. Cathelicidin (LL-37 and mCRAMP) is an antimicrobial peptide with an unknown role in obesity. We hypothesize that cathelicidin expression correlates with obesity and modulates fat mass and hepatic steatosis.

Materials and methods

Male C57BL/6 J mice were fed a high-fat diet. Streptozotocin was injected into mice to induce diabetes. Experimental groups were injected with cathelicidin and CD36 overexpressing lentiviruses. Human mesenteric fat adipocytes, mouse 3T3-L1 differentiated adipocytes and human HepG2 hepatocytes were used in the in vitro experiments. Cathelicidin levels in non-diabetic, prediabetic and type II diabetic patients were measured by enzyme-linked immunosorbent assay.

Results

Lentiviral cathelicidin overexpression reduced hepatic steatosis and decreased the fat mass of high-fat diet-treated diabetic mice. Cathelicidin overexpression reduced mesenteric fat and hepatic fatty acid translocase (CD36) expression that was reversed by lentiviral CD36 overexpression. Exposure of adipocytes and hepatocytes to cathelicidin significantly inhibited CD36 expression and reduced lipid accumulation. Serum cathelicidin protein levels were significantly increased in non-diabetic and prediabetic patients with obesity, compared with non-diabetic patients with normal body mass index (BMI) values. Prediabetic patients had lower serum cathelicidin protein levels than non-diabetic subjects.

Conclusions

Cathelicidin inhibits the CD36 fat receptor and lipid accumulation in adipocytes and hepatocytes, leading to a reduction of fat mass and hepatic steatosis in vivo. Circulating cathelicidin levels are associated with increased BMI. Our results demonstrate that cathelicidin modulates the development of obesity.

Recurrent GBM and AA have a dismal prognosis and a high unmet need for effective therapies. Toca 511 (vocimagene amiretrorepvec) is an investigational retroviral replicating vector that encodes the transgene cytosine deaminase (CD). Toca 511 selectively infects, persists and spreads in tumor. Subsequent oral administration of 5-fluorocytosine (Toca FC) produces 5-fluorouracil (5-FU) by CD within infected cells. 5-FU kills cancer cells and myeloid derived suppressor cells, inducing robust antitumor immune responses in animal models. Clinical data from phase 1 trials are consistent with this mechanism of action, and show extended survival compared to historical controls. Toca 5 is a multicenter, randomized, open-label Phase 2/3 trial of Toca 511 and Toca FC versus standard of care administered to patients undergoing resection for first or second recurrence of GBM or AA. Phase 2 will enroll 170 patients. Primary endpoint is overall survival (OS). Key secondary endpoints are safety, objective response rate, clinical benefit rate, progression-free survival, and landmark OS. Key inclusion criteria are age 18-75 years, histologically proven GBM or AA, measurable disease preoperatively of less than 5cm, candidate for equal or greater 80% resection of enhancing tumor based on pre-operative evaluation, and KPS equal or greater to 70. Assays for immune monitoring will be performed and molecular profiling of resected tumor samples will be correlated efficacy.

© Zou et al.Truncating mutations in the giant sarcomeric protein Titin result in dilated cardiomyopathy and skeletal myopathy. The most severely affected dilated cardiomyopathy patients harbor Titin truncations in the C-terminal two-thirds of the protein,