Enhanced recovery after elective spinal and peripheral nerve surgery: pilot study from a single institution
Ali ZS, Flanders TM, Ozturk AK, et al. Enhanced recovery after elective spinal and peripheral nerve surgery: Pilot study from a single institution. Journal of Neurosurgery: Spine SPI. 2019:1-9. https://dx.doi.org/10.3171/2018.9.SPINE18681.
Enhanced recovery after surgery (ERAS) protocols address pre-, peri-, and postoperative factors of a patient’s surgical journey. The authors sought to assess the effects of a novel ERAS protocol on clinical outcomes for patients undergoing elective spine or peripheral nerve surgery.
The authors conducted a prospective cohort analysis comparing clinical outcomes of patients undergoing elective spine or peripheral nerve surgery after implementation of the ERAS protocol compared to a historical control cohort in a tertiary care academic medical center. Patients in the historical cohort (September–December 2016) underwent traditional surgical care. Patients in the intervention group (April–June 2017) were enrolled in a unique ERAS protocol created by the Department of Neurosurgery at the University of Pennsylvania. Primary objectives were as follows: opioid and nonopioid pain medication consumption, need for opioid use at 1 month postoperatively, and patient-reported pain scores. Secondary objectives were as follows: mobilization and ambulation status, Foley catheter use, need for straight catheterization, length of stay, need for ICU admission, discharge status, and readmission within 30 days.
A total of 201 patients underwent surgical care via an ERAS protocol and were compared to a total of 74 patients undergoing traditional perioperative care (control group). The 2 groups were similar in baseline demographics. Intravenous opioid medications postoperatively via patient-controlled analgesia was nearly eliminated in the ERAS group (0.5% vs 54.1%, p < 0.001). This change was not associated with an increase in the average or daily pain scores in the ERAS group. At 1 month following surgery, a smaller proportion of patients in the ERAS group were using opioids (38.8% vs 52.7%, p = 0.041). The ERAS group demonstrated greater mobilization on postoperative day 0 (53.4% vs 17.1%, p < 0.001) and postoperative day 1 (84.1% vs 45.7%, p < 0.001) compared to the control group. Postoperative Foley use was decreased in the ERAS group (20.4% vs 47.3%, p < 0.001) without an increase in the rate of straight catheterization (8.1% vs 11.9%, p = 0.51).
Implementation of this novel ERAS pathway safely reduces patients’ postoperative opioid requirements during hospitalization and 1 month postoperatively. ERAS results in improved postoperative mobilization and ambulation.
Nondestructive tissue analysis for ex vivo and in vivo cancer diagnosis using a handheld mass spectrometry system
Zhang J, Rector J, Lin JQ, et al. Nondestructive tissue analysis for ex vivo and in vivo cancer diagnosis using a handheld mass spectrometry system. Science Translational Medicine. 2017;9(406). http://dx.doi.org/10.1126/scitranslmed.aan3968
Conventional methods for histopathologic tissue diagnosis are labor- and time-intensive and can delay decision-making during diagnostic and therapeutic procedures. We report the development of an automated and biocompatible handheld mass spectrometry device for rapid and nondestructive diagnosis of human cancer tissues. The device, named MasSpec Pen, enables controlled and automated delivery of a discrete water droplet to a tissue surface for efficient extraction of biomolecules. We used the MasSpec Pen for ex vivo molecular analysis of 20 human cancer thin tissue sections and 253 human patient tissue samples including normal and cancerous tissues from breast, lung, thyroid, and ovary. The mass spectra obtained presented rich molecular profiles characterized by a variety of potential cancer biomarkers identified as metabolites, lipids, and proteins. Statistical classifiers built from the histologically validated molecular database allowed cancer prediction with high sensitivity (96.4%), specificity (96.2%), and overall accuracy (96.3%), as well as prediction of benign and malignant thyroid tumors and different histologic subtypes of lung cancer. Notably, our classifier allowed accurate diagnosis of cancer in marginal tumor regions presenting mixed histologic composition. Last, we demonstrate that the MasSpec Pen is suited for in vivo cancer diagnosis during surgery performed in tumor-bearing mouse models, without causing any observable tissue harm or stress to the animal. Our results provide evidence that the MasSpec Pen could potentially be used as a clinical and intraoperative technology for ex vivo and in vivo cancer diagnosis.
Coached Peer Review: Developing the Next Generation of Authors
Sidalak D, Purdy E, Luckett-Gatopoulos S, Murray H, Thoma B, Chan TM. Coached peer review: Developing the next generation of authors. Academic Medicine. 2017;92(2):201-204. http://dx.doi.org/10.1097/ACM.0000000000001224.
Publishing in academic journals is challenging for learners. Those who pass the initial stages of internal review by an editor often find the anonymous peer review process harsh. Academic blogs offer alternate avenues for publishing medical education material. Many blogs, however, lack a peer review process, which some consumers argue compromises the quality of materials published.
CanadiEM (formerly BoringEM) is an academic educational emergency medicine blog dedicated to publishing high-quality materials produced by learners (i.e., residents and medical students). The editorial team has designed and implemented a collaborative “coached peer review” process that comprises an open exchange among the learner–author, editors, and reviewers. The goal of this process is to facilitate the publication of high-quality academic materials by learner–authors while providing focused feedback to help them develop academic writing skills.
The authors of this Innovation Report surveyed (February–June 2015) their blog’s learner–authors and external expert “staff” reviewers who had participated in coached peer review for their reactions to the process. The survey results revealed that participants viewed the process positively compared with both traditional journal peer review and academic blog publication processes. Participants found the process friendly, easy, efficient, and transparent. Learner–authors also reported increased confidence in their published material. These outcomes met the goals of coached peer review.
CanadiEM aims to inspire continued participation in, exposure to, and high quality production of academic writing by promoting the adoption of coached peer review for online educational resources produced by learners.
Checkpoint Kinase 2 Negatively Regulates Androgen Sensitivity and Prostate Cancer Cell Growth
Prostate cancer is the second leading cause of cancer death in American men, and curing metastatic disease remains a significant challenge. Nearly all patients with disseminated prostate cancer initially respond to androgen deprivation therapy (ADT), but virtually all patients will relapse and develop incurable castrationresistant prostate cancer (CRPC). A high-throughput RNAi screen to identify signaling pathways regulating prostate cancer cell growth led to our discovery that checkpoint kinase 2 (CHK2) knockdown dramatically increased prostate cancer growth and hypersensitized cells to low androgen levels. Mechanistic investigations revealed that the effects of CHK2 were dependent on the downstream signaling proteins CDC25C and CDK1. Moreover, CHK2depletion increased androgen receptor (AR) transcriptional activity on androgen-regulated genes, substantiating the finding that CHK2 affects prostate cancer proliferation, partly, through the AR. Remarkably, we further show that CHK2 is a novel ARrepressed gene, suggestive of a negative feedback loop between CHK2 and AR. In addition, we provide evidence that CHK2 physically associates with the AR and that cell-cycle inhibition increased this association. Finally, IHC analysis of CHK2 in prostate cancer patient samples demonstrated a decrease in CHK2 expression in high-grade tumors. In conclusion, we propose that CHK2 is a negative regulator of androgen sensitivity and prostate cancer growth, and that CHK2 signaling is lost during prostate cancer progression to castration resistance. Thus, perturbing CHK2 signaling may offer a new therapeutic approach for sensitizing CRPC to ADT and radiation.
Cancer Research. 12/1/2015, Vol. 75 Issue 23, p5093-5105. 13p.
Non-lethal Inhibition of Gut
Trimethylamine (TMA) N-oxide (TMAO), a gut-microbiota-dependent metabolite, both enhances atherosclerosis in animal models and is associated with cardiovascular risks in clinical studies. Here, we investigate the impact of targeted inhibition of the first step in TMAO generation, commensal microbial TMA production, on diet-induced atherosclerosis. A structural analog of choline, 3,3-dimethyl-1-butanol (DMB), is shown to non-lethally inhibit TMA formation from cultured microbes, to inhibit distinct microbial TMA lyases, and to both inhibit TMA production from physiologic polymicrobial cultures (e.g., intestinal contents, human feces) and reduce TMAO levels in mice fed a high-choline or L-carnitine diet. DMB inhibited choline diet-enhanced endogenous macrophage foam cell formation and atherosclerotic lesion development in apolipoprotein e−/− mice without alterations in circulating cholesterol levels. The present studies suggest that targeting gut microbial production of TMA specifically and non-lethal microbial inhibitors in general may serve as a potential therapeutic approach for the treatment of cardiometabolic diseases. •Gut microbial trimethylamine lyases are a therapeutic target for atherosclerosis•3,3-dimethyl-1-butanol inhibits microbial trimethylamine formation•3,3-dimethyl-1-butanol attenuates choline diet-enhanced atherosclerosis•Non-lethal gut microbial enzyme inhibition can impact host cardiometabolic phenotypes Drugging the gut microbiota with a non-lethal inhibitor that blocks production of the metabolite trimethylamine reduces the formation of atherosclerotic lesions and represents the first step toward treatment of cardiometabolic diseases by targeting the microbiome.
Cell 17 December 2015 163(7):1585-1595