Declaring a Patient Brain Dead on Extracorporeal Membrane Oxygenation (ECMO): Are There Guidelines or Misconceptions

Objectives: To review the clinical practice variations and trends with declaring patients brain dead on ECMO To highlight the need for the development of consensus guidelines to assist clinicians in the accurate diagnosis of brain death in this specific patient populatio

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Declaring Brain Death on ECMO

Purpose: Accumulating evidence suggests that organs from ECMO patients can be safely transplanted after a declaration of cardiac or brain death. However, making a diagnosis of brain death while a patient is on ECMO poses unique challenges and limited literature exists. We sought to describe the practice variations involved with declaring patients brain dead on ECMO by reviewing charts from our local organ procurement organization. Methods: After institutional review board approval, a retrospective chart review from our local organ procurement organization was performed to identify patients declared brain dead on ECMO who became organ donors. Between 1995 and 2014, we identified 26 patients on ECMO who donated organs after being diagnosed with brain death. Demographics, causes of death, clinical and ancillary studies used to pronounce brain death were recorded from charts. Results: All patients underwent one to two clinical exams as the initial step in the declaration of brain death. In addition to clinical examination, 15 (58%) of the patients underwent apnea testing, and of those, seven (47%) also had at least one ancillary test performed. Apnea testing was not utilized in 11 (42%) of the patients, and of those, nine (82%) had one or more ancillary tests performed to confirm brain death. Two (18%) patients underwent clinical examination only. Seventy-five percent of patients from 1995 - 2008 underwent apnea testing compared with only 50% of patients from 2009 to 2014. Conclusions: This study demonstrated the variability of practice patterns in the declaration of brain death for patients on ECMO over time and the lack of understanding of the CO2 physiology on ECMO. Additional studies are needed to devise a national standardized protocol to declare brain death on ECMO

Kidney micro-organoids in suspension culture as a scalable source of human pluripotent stem cell-derived kidney cells

Kidney organoids have potential uses in disease modelling, drug screening and regenerative medicine. However, novel cost-effective techniques are needed to enable scaled-up production of kidney cell types We describe here a modified suspension culture method for the generation of kidney micro-organoids from human pluripotent stem cells. Optimisation of differentiation conditions allowed the formation of micro-organoids, each containing six to ten nephrons that were surrounded by endothelial and stromal populations. Single cell transcriptional profiling confirmed the presence and transcriptional equivalence of all anticipated renal cell types consistent with a previous organoid culture method. This suspension culture micro-organoid methodology resulted in a three- to fourfold increase in final cell yield compared with static culture, thereby representing an economical approach to the production of kidney cells for various biological applications

Multimodal endovascular management of acute ischemic stroke in patients over 75 years old is safe and effective.

INTRODUCTION: Greater attention has been directed to endovascular recanalization of acute ischemic stroke in septuagenarians and above. TECHNIQUE: A retrospective chart review was conducted to include patients treated for acute ischemic stroke from 2006 to 2012. All patients underwent initial neurological assessment and non-contrast head CT. Patients treated from 2009 to 2012 additionally received emergent CT angiogram and CT perfusion. 51 patients met the clinical and radiographic criteria and underwent multimodal endovascular revascularization for acute ischemic events. RESULTS: All patients underwent cerebral angiography and met angiographic criteria for endovascular thrombolysis. 34 patients (67%) were older than 80 years of age. 23 patients (45%) received intravenous tissue plasminogen activator prior to admission. Eight (16%) patients underwent stent placement after intra-arterial thrombolysis, 10 (20%) underwent balloon angioplasty and seven (14%) underwent both angioplasty and stent placement. 21 (41%) required only intra-arterial thrombolytics. An improvement in Thrombolysis in Myocardial Infarction score was noted in 34 patients (67%). The average modified Rankin Scale score on discharge was 3.9. Symptomatic intracranial hemorrhage occurred in three patients (6%); none required surgery. One patient (1.9%) had a postoperative retroperitoneal hematoma, which was managed conservatively. Two fatalities resulted from intraoperative vessel rupture (3.9%), with a combined morbidity and mortality of 27.5%. CONCLUSIONS: Multimodal endovascular recanalization of acute ischemic stroke is a relatively safe treatment option in patients older than 75 years of age. Careful patient selection by clinical and radiographic inclusion criteria is necessary for the successful management of stroke in this age group

Pennsylvania comprehensive stroke center collaborative: Statement on the recently updated IV rt-PA prescriber information for acute ischemic stroke.

OBJECTIVE: Recently, the FDA guidelines regarding the eligibility of patients with acute ischemic stroke to receive IV rt-PA have been modified and are not in complete accord with the latest AHA/ASA guidelines. The resultant differences may result in discrepancies in patient selection for intravenous thrombolysis. METHODS: Several comprehensive stroke centers in the state of Pennsylvania have undertaken a collaborative effort to clarify and unify our own recommendations regarding how to reconcile these different guidelines. RESULTS: Seizure at onset of stroke, small previous strokes that are subacute or chronic, multilobar infarct involving more than one third of the middle cerebral artery territory on CT scan, hypoglycemia, minor or rapidly improving symptoms should not be considered as contraindications for intravenous thrombolysis. It is recommended to follow the AHA/ASA guidelines regarding blood pressure management and bleeding diathesis. Patients receiving factor Xa inhibitors and direct thrombin inhibitors within the preceding 48h should be excluded from receiving IV rt-PA. CT angiography is effective in identifying candidates for endovascular therapy. Consultation with and/or transfer to a comprehensive stroke center should be an option where indicated. Patients should receive IV rt-PA up to 4.5h after the onset of stroke. CONCLUSIONS: The process of identifying patients who will benefit the most from IV rt-PA is still evolving. Considering the rapidity with which patients need to be evaluated and treated, it remains imperative that systems of care adopt protocols to quickly gather the necessary data and have access to expert consultation as necessary to facilitate best practices

CXCR4 Regulates Extra-Medullary Myeloma through Epithelial-Mesenchymal-Transition-like Transcriptional Activation

Extra-medullary disease (EMD) in multiple myeloma (MM) is associated with poor prognosis and resistance to chemotherapy. However, molecular alterations that lead to EMD have not been well defined. We developed bone marrow (BM)- and EMD-prone MM syngeneic cell lines; identified that epithelial-to-mesenchymal transition (EMT) transcriptional patterns were significantly enriched in both clones compared to parental cells, together with higher levels of CXCR4 protein; and demonstrated that CXCR4 enhanced the acquisition of an EMT-like phenotype in MM cells with a phenotypic conversion for invasion, leading to higher bone metastasis and EMD dissemination in vivo. In contrast, CXCR4 silencing led to inhibited tumor growth and reduced survival. Ulocuplumab, a monoclonal anti-CXCR4 antibody, inhibited MM cell dissemination, supported by suppression of the CXCR4-driven EMT-like phenotype. These results suggest that targeting CXCR4 may act as a regulator of EMD through EMT-like transcriptional modulation, thus representing a potential therapeutic strategy to prevent MM disease progression

Assessment of Complications After Pancreatic Surgery: A Novel Grading System Applied to 633 Patients Undergoing Pancreaticoduodenectomy

OBJECTIVE: To define a simple and reproducible classification of complications following pancreaticoduodenectomy (PD) based on a therapy-oriented severity grading system. BACKGROUND: While mortality is rare after PD, morbidity rates remain high. The lack of standardization in evaluating morbidity after PD has severely hampered meaningful comparisons over time and among centers. We adapted a novel classification of complication to stratify morbidity by severity after PD, to test whether the incidence of pancreatic fistula has changed over time, and to identify risk factors in a single North American center. METHODS: The classification was applied to a consecutive series of 633 patients undergoing PD between February 2003 and August 2005. Another series of 141 patients treated between 1987 and 1990 was also analyzed to identify changes in the incidence and severity of fistula. Univariate and multivariate analyses were performed to link respective complications with preoperative and intraoperative parameters, length of hospital stay, and long-term survival. RESULTS: A total of 263 (41.5%) patients did not develop any complication, while 370 (58.5%) had at least one complication; 62 (10.0%) patients had only grade I complications (no need for specific intervention), 192 patients (30.0%) had grade II (need for drug therapy such as antibiotics), 85 patients (13.5%) had grade III (need for invasive therapy), and 19 patients (3.0%) had grade IV complications (organ dysfunction with ICU stay). Grade V (death) occurred in 12 patients (2.0%). A total of 57 patients (9.0%) developed pancreatic fistula, of which 33 (58.0%) were classified as grade II, 17 (30.0%) as grade III, 5 (9.0%) as grade IV, and 2 (3.5%) as grade V. Delayed gastric emptying was documented in 80 patients (12.7%); half of them were scored as grade II and the other half as grade III. A significant decrease in the incidence of fistula was observed between the 2 periods analyzed (14.0% vs. 9.0%, P < 0.001), mostly due to a decrease in grade II fistula. Cardiovascular disease was a risk factor for overall morbidity and complication severity, while texture of the gland and cardiovascular disease were risk factors for pancreatic fistula. CONCLUSION: This study demonstrates the applicability and utility of a new classification in grading complications following pancreatic surgery. This novel approach may provide a standardized, objective, and reproducible assessment of pancreas surgery enabling meaningful comparison among centers and over time