Integrated generation of induced pluripotent stem cells in a low-cost device.

Human induced pluripotent stem cells (iPSCs) have unlimited proliferation capability and potential to differentiate into all somatic cells. Their derivatives contain patients' genetic information and can model many diseases. Additionally, derivatives of patient-specific iPSCs induce minimal immune rejection in vivo. With this unique combination of properties, iPSCs open the avenue to personalized medicine including personalized drug screening, toxicity test, cell therapy and tissue engineering. However, the further advance of iPSC-based personalized medicine is currently limited by the difficulty to generate iPSCs for large populations and at affordable cost. We here report a low-cost device to address this challenge. The device allows the entire bioprocess for generating high quality and quantity of iPSCs for one patient to be done automatically within a closed conical tube without cell passaging. Additionally, iPSCs can be further differentiated into somatic cells in the device. Thus, the device also allows integrated iPSCs generation, expansion and differentiation to produce any somatic cell types. This device can be made in large quantities at low cost for manufacturing iPSCs (and their derivatives in necessary) for large populations at affordable cost. It will significantly advance the iPSCs-based personalized medicine.

Association of a Frailty Screening Initiative With Postoperative Survival at 30, 180, and 365 Days.

Importance: As the US population ages, the number of operations performed on elderly patients will likely increase. Frailty predicts postoperative mortality and morbidity more than age alone, thus presenting opportunities to identify the highest-risk surgical patients and improve their outcomes. Objective: To examine the effect of the Frailty Screening Initiative (FSI) on mortality and complications by comparing the surgical outcomes of a cohort of surgical patients treated before and after implementation of the FSI. Design, Setting, and Participants: This single-site, facility-wide, prospective cohort quality improvement project studied all 9153 patients from a level 1b Veterans Affairs medical center who presented for major, elective, noncardiac surgery from October 1, 2007, to July 1, 2014. Interventions: Assessment of preoperative frailty in all patients scheduled for elective surgery began in July 2011. Frailty was assessed with the Risk Analysis Index (RAI), and the records of all frail patients (RAI score, ≥21) were flagged for administrative review by the chief of surgery (or designee) before the scheduled operation. On the basis of this review, clinicians from surgery, anesthesia, critical care, and palliative care were notified of the patient's frailty and associated surgical risks; if indicated, perioperative plans were modified based on team input. Main Outcomes and Measures: Postoperative mortality at 30, 180, and 365 days. Results: From October 1, 2007, to July 1, 2014, a total of 9153 patients underwent surgery (mean [SD] age, 60.3 [13.5] years; female, 653 [7.1%]; and white, 7096 [79.8%]). Overall 30-day mortality decreased from 1.6% (84 of 5275 patients) to 0.7% (26 of 3878 patients, P < .001) after FSI implementation. Improvement was greatest among frail patients (12.2% [24 of 197 patients] to 3.8% [16 of 424 patients], P < .001), although mortality rates also decreased among the robust patients (1.2% [60 of 5078 patients] to 0.3% [10 of 3454 patients], P < .001). The magnitude of improvement among frail patients increased at 180 (23.9% [47 of 197 patients] to 7.7% [30 of 389 patients], P < .001) and 365 days (34.5% [68 of 197 patients] to 11.7% [36 of 309 patients], P < .001). Multivariable models revealed improved survival after FSI implementation, controlling for age, frailty, and predicted mortality (adjusted odds ratio for 180-day survival, 2.87; 95% CI, 1.98-4.16). Conclusions and Relevance: Implementation of the FSI was associated with reduced mortality, suggesting the feasibility of widespread screening of patients preoperatively to identify frailty and the efficacy of system-level initiatives aimed at improving their surgical outcomes. Additional investigation is required to establish a causal connection.

Development and Initial Validation of the Risk Analysis Index for Measuring Frailty in Surgical Populations.

Importance: Growing consensus suggests that frailty-associated risks should inform shared surgical decision making. However, it is not clear how best to screen for frailty in preoperative surgical populations. Objective: To develop and validate the Risk Analysis Index (RAI), a 14-item instrument used to measure surgical frailty. It can be calculated prospectively (RAI-C), using a clinical questionnaire, or retrospectively (RAI-A), using variables from the surgical quality improvement databases (Veterans Affairs or American College of Surgeons National Surgical Quality Improvement Projects). Design, Setting, and Participants: Single-site, prospective cohort from July 2011 to September 2015 at the Veterans Affairs Nebraska-Western Iowa Heath Care System, a Level 1b Veterans Affairs Medical Center. The study included all patients presenting to the medical center for elective surgery. Exposures: We assessed the RAI-C for all patients scheduled for surgery, linking these scores to administrative and quality improvement data to calculate the RAI-A and the modified Frailty Index. Main Outcomes and Measures: Receiver operator characteristics and C statistics for each measure predicting postoperative mortality and morbidity. Results: Of the participants, the mean (SD) age was 60.7 (13.9) years and 249 participants (3.6%) were women. We assessed the RAI-C 10 698 times, from which we linked 6856 unique patients to mortality data. The C statistic predicting 180-day mortality for the RAI-C was 0.772. Of these 6856 unique patients, we linked 2785 to local Veterans Affairs Surgeons National Surgical Quality Improvement Projects data and calculated the C statistic for both the RAI-A (0.823) and RAI-C (0.824), along with the correlation between the 2 scores (r = 0.478; P < .001). Of these 2785 patients, there were sufficient data to calculate the modified Frailty Index for 1021, in which the C statistics were 0.865 (RAI-A), 0.797 (RAI-C), and 0.811 (modified Frailty Index). The correlation between the RAI-A and RAI-C was 0.547, and the correlations of the modified Frailty Index to the RAI-A and RAI-C were 0.301 and 0.269, respectively (all P < .001). A cutoff of RAI-C of at least 21 classified 18.3% patients as "frail" with a sensitivity of 0.50 and specificity of 0.82, whereas the RAI-A was less sensitive (0.25) and more specific (0.97), classifying only 3.7% as "frail." Conclusions and Relevance: The RAI-C and RAI-A represent effective tools for measuring frailty in surgical populations with predictive ability on par with other frailty tools. Moderate correlation between the measures suggests convergent validity. The RAI-C offers the advantage of prospective, preoperative assessment that is proved feasible for large-scale screening in clinical practice. However, further efforts should be directed at determining the optimal components of preoperative frailty assessment.

Selective use of esophageal manometry and 24-Hour pH monitoring before laparoscopic fundoplication.

BACKGROUND: Preoperative esophageal manometry and 24-hour pH monitoring commonly are used in preoperative evaluation of patients undergoing fundoplication. Here we review our experience with the selective preoperative workup of patients undergoing fundoplication to treat gastroesophageal reflux disease. STUDY DESIGN: A series of 628 consecutive antireflux procedures was reviewed. History and physical examination, upper endoscopy, and upper gastrointestinal videofluoroscopy were obtained preoperatively on all patients; the first 30 patients also underwent esophageal manometry and pH monitoring (routine evaluation group). Thereafter, pH monitoring only was performed for atypical reflux symptoms, and manometry only was performed for a history of dysphagia, odynophagia, or for abnormal motility on videofluoroscopy (selective evaluation group). All patients underwent a laparoscopic floppy Nissen fundoplication, and then endoscopy and fluoroscopy at 3 months and 12 months postoperatively. RESULTS: Eighty-five of the patients in the selective evaluation group (14%) required manometry, and 88 (15%) underwent pH monitoring. Eighteen of the 115 patients who underwent manometry (16%) had evidence of dysmotility. None of these 18 patients had increased dysphagia postoperatively; 8 of 18 reported improvement with swallowing. Five patients in the selective group (0.8%) had persistent postoperative dysphagia caused by technical error (four patients) or with no identifiable cause (one patient). The estimated charge or collection reduction with use of the selective evaluation was 1,253,100 US dollars or 395,000 US dollars, respectively. CONCLUSIONS: Selective use of manometry and pH monitoring was cost effective and safe in this series. Although esophageal manometry and 24-hour pH monitoring might be necessary with abnormal findings on videofluoroscopy or atypical symptoms, in our experience, their routine use is not essential in preoperative evaluation of patients undergoing fundoplication for gastroesophageal reflux disease.