James G. Hecker
University of Pennsylvania · Rehabilitation Medicine
Active 1974–2023
Research topics
- Medicine
- Biology
- Cell biology
- Molecular biology
- Chemistry
Selected publications
Assessment of aerosol persistence in ICUs via low-cost sensor network and zonal models
Scientific Reports · 2023-03-10 · 7 citations
articleOpen accessThe COVID-19 pandemic raised public awareness about airborne particulate matter (PM) due to the spread of infectious diseases via the respiratory route. The persistence of potentially infectious aerosols in public spaces and the spread of nosocomial infections in medical settings deserve careful investigation; however, a systematic approach characterizing the fate of aerosols in clinical environments has not been reported. This paper presents a methodology for mapping aerosol propagation using a low-cost PM sensor network in ICU and adjacent environments and the subsequent development of the data-driven zonal model. Mimicking aerosol generation by a patient, we generated trace NaCl aerosols and monitored their propagation in the environment. In positive (closed door) and neutral-pressure (open door) ICUs, up to 6% or 19%, respectively, of all PM escaped through the door gaps; however, the outside sensors did not register an aerosol spike in negative-pressure ICUs. The K-means clustering analysis of temporospatial aerosol concentration data suggests that ICU can be represented by three distinct zones: (1) near the aerosol source, (2) room periphery, and (3) outside the room. The data suggests two-phase plume behavior: dispersion of the original aerosol spike throughout the room, followed by an evacuation phase where "well-mixed" aerosol concentration decayed uniformly. Decay rates were calculated for positive, neutral, and negative pressure operations, with negative-pressure rooms clearing out nearly twice as fast. These decay trends closely followed the air exchange rates. This research demonstrates the methodology for aerosol monitoring in medical settings. This study is limited by a relatively small data set and is specific to single-occupancy ICU rooms. Future work needs to evaluate medical settings with high risks of infectious disease transmission.
Non-Viral Delivery of RNA Gene Therapy to the Central Nervous System
Pharmaceutics · 2022-01-11 · 19 citations
reviewOpen accessSenior authorAppropriate gene delivery systems are essential for successful gene therapy in clinical medicine. Lipid-mediated nucleic acid delivery is an alternative to viral vector-mediated gene delivery and has the following advantages. Lipid-mediated delivery of DNA or mRNA is usually more rapid than viral-mediated delivery, offers a larger payload, and has a nearly zero risk of incorporation. Lipid-mediated delivery of DNA or RNA is therefore preferable to viral DNA delivery in those clinical applications that do not require long-term expression for chronic conditions. Delivery of RNA may be preferable to non-viral DNA delivery in some clinical applications, since transit across the nuclear membrane is not necessary, and onset of expression with RNA is therefore even faster than with DNA, although both are faster than most viral vectors. Delivery of RNA to target organ(s) has previously been challenging due to RNA's rapid degradation in biological systems, but cationic lipids complexed with RNA, as well as lipid nanoparticles (LNPs), have allowed for delivery and expression of the complexed RNA both in vitro and in vivo. This review will focus on the non-viral lipid-mediated delivery of RNAs, including mRNA, siRNA, shRNA, and microRNA, to the central nervous system (CNS), an organ with at least two unique challenges. The CNS contains a large number of slowly dividing or non-dividing cell types and is protected by the blood brain barrier (BBB). In non-dividing cells, RNA-lipid complexes demonstrated increased transfection efficiency relative to DNA transfection. The efficiency, timing of the onset, and duration of expression after transfection may determine which nucleic acid is best for which proposed therapy. Expression can be seen as soon as 1 h after RNA delivery, but duration of expression has been limited to 5-7 h. In contrast, transfection with a DNA lipoplex demonstrates protein expression within 5 h and lasts as long as several weeks after transfection.
Measuring aerosols in the operating theatre and beyond using a real‐time sensor network
Anaesthesia · 2022-09-01 · 9 citations
article1st authorCorrespondingThe ability to measure and track aerosols in the vicinity of patients with suspected or confirmed COVID-19 is highly desirable. At present, there is no way to measure and track, in real time, the sizes, dispersion and dilution/disappearance of aerosols that are generated by airway manipulations such as mask ventilation; tracheal intubation; bronchoscopy; dental and gastro-intestinal endoscopy procedures; or by vigorous breathing, coughing or exercise. We deployed low-cost photoelectric sensors in five operating theatres between surgical cases. We measured and analysed dilution and exfiltration of aerosols we generated to evaluate air handling and dispersion under real-world conditions. These data were used to develop a model of aerosol persistence. We found significant variation between different operating theatres. Equipment placement near air vents affects air flows, impacting aerosol movement and elimination patterns. Despite these impediments, air exchange in operating theatres is robust and prolonged fallow time before theatre turnover may not be necessary. Significant concentrations of aerosols are not seen in adjoining areas outside of the operating theatre. These models and dispersion rates can predict aerosol persistence in operating theatres and other clinical areas and potentially facilitate quantification of risk, with obvious and far-reaching implications for designing, evaluating and confirming air handling in non-medical environments.
Journal of Neurosurgical Anesthesiology · 2021-01-19 · 14 citations
articleSenior authorCorrespondingINTRODUCTION: The incidence and quantification of inadvertent electroencephalographic burst suppression during total intravenous anesthesia (TIVA) for spine instrumentation surgery has not previously been reported. METHODS: The primary aim of this retrospective observational quality improvement project was to establish the prevalence of burst suppression during spine instrumentation surgery with TIVA. The secondary outcome was the incidence of postoperative delirium. RESULTS: One hundred twelve consecutive patients, aged between 20 and 88 years, underwent spinal instrumentation surgery. Seventy-eight (69.6%) patients experienced inadvertent burst suppression; the maximal degree of burst suppression ratio was 20% to 100%. Median (interquartile range [IQR]) time spent in burst suppression was 44 (77) minutes, and burst suppression was present for 22% (range: 2% to 93%) of the monitoring period. Average (±SD) propofol dose was lower in patients with burst suppression (87±19 vs. 93±15 µg/kg/min, P=0.04). Ten (8.9%) patients experienced postoperative delirium. Intraoperative burst suppression was more prevalent in those that experienced delirium (100% vs. 66.7%, P=0.03, relative risk: 1.5, 95% confidence interval: 1.3-1.7). The proportion of the monitoring period spent in maximal burst suppression (15.3 [25.9]% vs.11.7 [21.7]%) was similar between those that did, and did not, experience delirium. CONCLUSIONS: High rates and prolonged periods of inadvertent burst suppression may be prevalent during spine instrumentation surgery with TIVA. Our findings suggest that usage of electroencephalography alone is incomplete without prompt interpretation and intervention, mandating close communication between neuromonitoring and anesthesia teams. The dose-response relationship between burst suppression, total time spent in maximal burst suppression, and their association with delirium warrants further evaluation.
Gene Therapy for Neuroanesthesia
2019-01-01
book-chapterSenior authorCorrespondingIncidence and Risk Factors for Intraoperative Seizures During Elective Craniotomy
Journal of Neurosurgical Anesthesiology · 2018-04-24 · 17 citations
articleCorrespondingBACKGROUND: Perioperative seizures may affect 1% to 50% of patients undergoing craniotomy and adversely impact outcomes. However, data on intraoperative seizures are limited. This retrospective case-control study investigated the incidence and risk factors for intraoperative seizures during elective supratentorial craniotomy involving evoked potential monitoring. MATERIALS AND METHODS: Patients aged 18 years or above undergoing elective supratentorial craniotomy with evoked potential monitoring who experienced intraoperative seizures at our institution between December 2008 and March 2014 were compared with a control group generated using a random number generator. Six controls were used for each case from among the patients who underwent elective supratentorial craniotomy during the same calendar year. Multivariate analysis was conducted using logistic regression to identify the risk factors for intraoperative seizures. RESULTS: Among the 1916 patients who met the inclusion criteria, 45 (2.3%) had intraoperative seizures. The majority of seizures occurred during burr-hole placement or craniotomy, before lesion manipulation. Timing of seizures relative to motor evoked potential runs and stimulus intensity was variable. Significant risk factors for intraoperative seizures were seizure history (odds ratio [OR], 2.18; 95% confidence interval [CI], 1.07-4.46; P=0.03), diagnosis of brain tumor (OR, 2.41; 95% CI, 1.16-4.19; P=0.02), and temporal craniotomy (OR, 5.18; 95% CI, 2.03-13.25; P=0.001). Intraoperative prophylactic use of phenytoin/fosphenytoin and levetiracetam was protective against seizure (phenytoin/fosphenytoin: OR, 0.12; 95% CI, 0.04-0.35; P<0.001 and levetiracetam: OR, 0.40; 95% CI, 0.17-0.94; P=0.04). Phenytoin/fosphenytoin was more protective than levetiracetam (OR, 0.31; 95% CI, 0.10-0.99; P=0.048). CONCLUSIONS: The overall incidence of intraoperative seizures was 2.3%. Independent risk factors for intraoperative seizures were seizure history, diagnosis of intracranial tumor, and temporal craniotomy. Intraoperative prophylactic anticonvulsant use was protective.
World Neurosurgery · 2016-01-13 · 65 citations
articleOpen accessEducational Resources in Neuroanesthesiology
ASA Monitor · 2015-09-01
articleMethods in molecular biology · 2015-11-26 · 29 citations
article1st authorCorresponding. Cerebral Ischemia and Neuroprotection
Oxford University Press eBooks · 2013-11-01 · 3 citations
book-chapter1st authorCorrespondingAbstract The authors discuss clinical management of neurosurgical problems with special emphasis on challenges after an ischemic event and rapid implementation of appropriate therapies. Neurosurgical anesthesiology requires that the anesthesiologist have an understanding of neuroanatomy, neurophysiology, and the surgical procedure. Guidelines for management and key points will be highlighted. They offer a summary of contemporary advances in knowledge about secondary injury. These include novel strategies of postischemia resuscitation that attenuate secondary injury. Finally, they explore exciting ideas that have the potential to provide a comprehensive model for the central nervous system in normal physiology and pathophysiology and to offer the possibility of prophylactic therapies.
Recent grants
NIH · $643k · 2005
NIH · $1.7M · 2009
Frequent coauthors
- 14 shared
Michael H. Nantz
University of Louisville
- 10 shared
Shaomin Zou
Sun Yat-sen University
- 7 shared
Ellen Hauck
- 7 shared
Deepak Sharma
- 5 shared
Igor Novosselov
University of Washington
- 5 shared
R. Rochlin
University of Washington
- 5 shared
K. Glenn
Northwestern Memorial Hospital
- 5 shared
Keith Scarfo
Rhode Island Hospital
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