IMPORTANCE Hospital cooling improves outcome after cardiac arrest, but prehospital cooling immediately after return of spontaneous circulation may result in better outcomes. OBJECTIVE To determine ...whether prehospital cooling improves outcomes after resuscitation from cardiac arrest in patients with ventricular fibrillation (VF) and without VF. DESIGN, SETTING, AND PARTICIPANTS A randomized clinical trial that assigned adults with prehospital cardiac arrest to standard care with or without prehospital cooling, accomplished by infusing up to 2 L of 4°C normal saline as soon as possible following return of spontaneous circulation. Adults in King County, Washington, with prehospital cardiac arrest and resuscitated by paramedics were eligible and 1359 patients (583 with VF and 776 without VF) were randomized between December 15, 2007, and December 7, 2012. Patient follow-up was completed by May 1, 2013. Nearly all of the patients resuscitated from VF and admitted to the hospital received hospital cooling regardless of their randomization. MAIN OUTCOMES AND MEASURES The primary outcomes were survival to hospital discharge and neurological status at discharge. RESULTS The intervention decreased mean core temperature by 1.20°C (95% CI, −1.33°C to −1.07°C) in patients with VF and by 1.30°C (95% CI, −1.40°C to −1.20°C) in patients without VF by hospital arrival and reduced the time to achieve a temperature of less than 34°C by about 1 hour compared with the control group. However, survival to hospital discharge was similar among the intervention and control groups among patients with VF (62.7% 95% CI, 57.0%-68.0% vs 64.3% 95% CI, 58.6%-69.5%, respectively; P = .69) and among patients without VF (19.2% 95% CI, 15.6%-23.4% vs 16.3% 95% CI, 12.9%-20.4%, respectively; P = .30). The intervention was also not associated with improved neurological status of full recovery or mild impairment at discharge for either patients with VF (57.5% 95% CI, 51.8%-63.1% of cases had full recovery or mild impairment vs 61.9% 95% CI, 56.2%-67.2% of controls; P = .69) or those without VF (14.4% 95% CI, 11.3%-18.2% of cases vs 13.4% 95% CI,10.4%-17.2% of controls; P = .30). Overall, the intervention group experienced rearrest in the field more than the control group (26% 95% CI, 22%-29% vs 21% 95% CI, 18%-24%, respectively; P = .008), as well as increased diuretic use and pulmonary edema on first chest x-ray, which resolved within 24 hours after admission. CONCLUSION AND RELEVANCE Although use of prehospital cooling reduced core temperature by hospital arrival and reduced the time to reach a temperature of 34°C, it did not improve survival or neurological status among patients resuscitated from prehospital VF or those without VF. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00391469
An open-label, first-in-human phase 1/2 study is being conducted to evaluate the safety and efficacy of pancreatic endoderm cells (PECs) implanted in non-immunoprotective macroencapsulation devices ...for the treatment of type 1 diabetes. We report an analysis on 1 year of data from the first cohort of 15 patients from a single trial site that received subcutaneous implantation of cell products combined with an immunosuppressive regimen. Implants were well tolerated with no teratoma formation or severe graft-related adverse events. After implantation, patients had increased fasting C-peptide levels and increased glucose-responsive C-peptide levels and developed mixed meal-stimulated C-peptide secretion. There were immunosuppression-related transient increases in circulating regulatory T cells, PD1
T cells, and IL17A
CD4
T cells. Explanted grafts contained cells with a mature β cell phenotype that were immunoreactive for insulin, islet amyloid polypeptide, and MAFA. These data, and associated findings (Shapiro et al., 2021), are the first reported evidence of meal-regulated insulin secretion by differentiated stem cells in patients.
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis, particularly for patients with metastatic disease. Treatment for oligometastatic presentation has been ...reported in recent literature, but the role of intraperitoneal chemotherapy for patients with peritoneal metastases (PM) remains unclear. We performed a systematic literature search of the PubMed, Cochrane and Embase databases in order to identify clinical trials and case-series reporting on the safety and efficacy of intraperitoneal chemotherapy in patients with PDAC-derived PM. Eight publications reporting on 85 patients were identified, using three different therapeutic strategies. First, 37 patients received cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for PDAC with PM. Grade 3 and 4 complications occurred in 37.8% of patients, without perioperative mortality. Median disease-free survival and overall survival (OS) rates varied from 4 to 36 months and 4 to 62 months, respectively. Secondly, 40 patients with resectable PDAC without PM received prophylactic HIPEC following pancreatic resection, with postoperative morbidity and mortality rates of 30% and 5%, and 5-year OS rates of 23–24%. Finally, eight patients with PDAC-derived peritoneal disease were converted to resectable disease after receiving neoadjuvant intraperitoneal chemotherapy and operated on with curative intent, achieving a median OS of 27.8 months. In conclusion, CRS with HIPEC for PDAC-derived PM appears to be safe, conferring the same postoperative morbidity and mortality as reported on non-pancreatic malignancies. In highly selected patients, it could be considered for short-term disease control. However, long-term survival remains poor. The addition of prophylactic HIPEC for resectable PDAC cannot be recommended.
Background
Despite reduced perioperative mortality and routine use of adjuvant therapy following pancreatectomy for pancreatic ductal adenocarcinoma (PDAC), improvement in long-term outcome has been ...difficult to ascertain. This study compares outcomes in patients undergoing resection for PDAC within a single, high-volume academic institution over two sequential time periods.
Methods
Retrospective review of patients with resected PDAC, in two cohorts: period 1 (P1), 1991–2000; and period 2 (P2), 2001–2010. Univariate and multivariate analyses using the Cox proportional hazards model were performed to determine prognostic factors associated with long-term survival. Survival was evaluated using Kaplan–Meier analyses.
Results
A total of 179 pancreatectomies were performed during P1 and 310 during P2. Perioperative mortality was 6.7 % (12/179) in P1 and 1.6 % (5/310) in P2 (
p
= 0.003). P2 had a greater number of lymph nodes resected (17 0–50 vs. 7 0–31;
p
< 0.001), and a higher lymph node positivity rate (69 % 215/310 vs. 58 % 104/179;
p
= 0.021) compared with P1. The adjuvant therapy rate was 30 % (53/179) in P1 and 63 % (195/310) in P2 (
p
< 0.001). By multivariate analysis, node and margin status, tumor grade, adjuvant therapy, and time period of resection were independently associated with overall survival (OS) for both time periods. Median OS was 16 months (95 % confidence interval CI 14–20) in P1 and 27 months (95 % CI 24–30) in P2 (
p
< 0.001).
Conclusions
Factors associated with improved long-term survival remain comparable over time. Short- and long-term survival for patients with resected PDAC has improved over time due to decreased perioperative mortality and increased use of adjuvant therapy, although the proportion of 5-year survivors remains small.
Macroencapsulated pancreatic endoderm cells (PECs) can reverse diabetes in rodents and preclinical studies revealed that thyroid hormones in vitro and in vivo bias PECs to differentiate into ...insulin-producing cells. In an ongoing clinical trial, PECs implanted in macroencapsulation devices into patients with type 1 diabetes were safe but yielded heterogeneous outcomes. Though most patients developed meal responsive C-peptide, levels were heterogeneous and explanted grafts had variable numbers of surviving cells with variable distribution of endocrine cells.
We measured circulating triiodothyronine and thyroxine levels in all patients treated at 1 of the 7 sites of the ongoing clinical trial and determined if thyroid hormone levels were associated with the C-peptide or glucagon levels and cell fate of implanted PECs.
Both triiodothyronine and thyroxine levels were significantly associated with the proportion of cells that adopted an insulin-producing fate with a mature phenotype. Thyroid hormone levels were inversely correlated to circulating glucagon levels after implantation, suggesting that thyroid hormones lead PECs to favor an insulin-producing fate over a glucagon-producing fate. In mice, hyperthyroidism led to more rapid maturation of PECs into insulin-producing cells similar in phenotype to PECs in euthyroid mice.
These data highlight the relevance of thyroid hormones in the context of PEC therapy in patients with type 1 diabetes and suggest that a thyroid hormone adjuvant therapy may optimize cell outcomes in some PEC recipients.
Living donor liver transplant (LDLT) accounts for a small volume of the transplants in the USA. Due to the current liver allocation system based on the model for end-stage liver disease (MELD), LDLT ...has a unique role in providing life-saving transplantation for patients with low MELD scores and significant complications from portal hypertension, as well as select patients with hepatocellular carcinoma (HCC). Donor safety is paramount and has been a topic of much discussion in the transplant community as well as the general media. The donor risk appears to be low overall, with a favorable long-term quality of life. The latest trend has been a gradual shift from right-lobe grafts to left-lobe grafts to reduce donor risk, provided that the left lobe can provide adequate liver volume for the recipient.
OBJECTIVE:To compare the efficacy and safety of patient-controlled analgesia (PCA) to epidural analgesia in adults undergoing open hepatic resection.
BACKGROUND:Effective pain management in patients ...undergoing open hepatic resection is often achieved with epidural analgesia. However, associated risks have prompted investigation of alternative analgesic methods in this patient population.
METHODS:A comprehensive systematic literature review via Medline, Embase, and the Cochrane databases from inception until December 2, 2017 was conducted, followed by meta-analysis. Abstract and full-text screening, data extraction, and quality assessment were conducted by 2 investigators. Odds ratios (OR), mean differences (MD), and 95% confidence intervals were calculated using RevMan 5.3.
RESULTS:Four randomized controlled trials with 278 patients were identified. All studies compared the use of PCA to epidural, with differing regimens. Pooled MD and 95% confidence interval for pain score were higher for PCA at rest 24 hours postoperatively (0.59 0.30, 0.88), and with movement at 48 hours postoperatively (0.95 0.31, 1.60. Pooled MD for hospital length of stay was 1.23 days (−2.72, 5.19). Pooled OR was 0.68 (0.36, 1.3) and 0.24 (0.04, 1.36) for overall and analgesia-related complications, respectively. Need for blood transfusion had a pooled OR of 1.14 (0.31, 4.18).
CONCLUSIONS:Epidural analgesia was observed to be superior to PCA for pain control in patients undergoing open hepatic resection, with no significant difference in hospital length of stay, complications, or transfusion requirements. Thus, epidural analgesia should be the preferred method for the management of postoperative pain in this patient population.
Background
The purpose of this study was to evaluate a single-institution experience with delivery of preoperative therapy to patients with pancreatic ductal adenocarcinoma (PDAC) prior to ...pancreatoduodenectomy (PD).
Methods
Consecutive patients (622) with PDAC who underwent PD following chemotherapy and/or chemoradiation between 1990 and 2014 were retrospectively reviewed. Preoperative treatment regimens, clinicopathologic characteristics, operative details, and long-term outcomes in four successive time periods (1990–1999, 2000–2004, 2005–2009, 2010–2014) were evaluated and compared.
Results
The average number of patients per year who underwent PD following preoperative therapy as well as the proportion of operations performed for borderline resectable and locally advanced (BR/LA) tumors increased over time. The use of induction systemic chemotherapy, as well as postoperative adjuvant chemotherapy, also increased over time. Throughout the study period, the mean EBL decreased while R0 margin rates and vascular resection rates increased overall. Despite the increase in BR/LA resections, locoregional recurrence (LR) rates remained similar over time, and overall survival (OS) improved significantly (median 24.1, 28.1, 37.3, 43.4 months, respectively, p < 0.0001).
Conclusions
Despite increases in case complexity, relatively low rates of LR have been maintained while significant improvements in OS have been observed. Further improvements in patient outcomes will likely require disruptive advances in systemic therapy.
Magnetoresistive (MR) sensors have been identified as promising candidates for the development of high-performance magnetometers due to their high sensitivity, low cost, low power consumption, and ...small size. The rapid advance of MR sensor technology has opened up a variety of MR sensor applications. These applications are in different areas that require MR sensors with different properties. Future MR sensor development in each of these areas requires an overview and a strategic guide. An MR sensor roadmap (non-recording applications) was therefore developed and made public by the Technical Committee of the IEEE Magnetics Society with the aim to provide an research and development (R&D) guide for MR sensors intended to be used by industry, government, and academia. The roadmap was developed over a three-year period and coordinated by an international effort of 22 taskforce members from ten countries and 17 organizations, including universities, research institutes, and sensor companies. In this paper, the current status of MR sensors for non-recording applications was identified by analyzing the patent and publication statistics. As a result, timescales for MR sensor development were established and critical milestones for sensor parameters were extracted in order to gain insight into potential MR sensor applications (non-recording). Five application areas were identified, and five MR sensor roadmaps were established. These include biomedical applications, flexible electronics, position sensing and human-computer interactions, non-destructive evaluation and monitoring, and navigation and transportation. Each roadmap was analyzed using a logistic growth model, and new opportunities were predicted based on the extrapolated curve, forecast milestones, and professional judgment of the taskforce members. This paper provides a framework for MR sensor technology (non-recording applications) to be used for public and private R&D planning, in order to provide guidance into likely MR sensor applications, products, and services expected in the next 15 years and beyond.
PDF
