bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term patient-reported outcomes and patient-reported outcome measures after injury: the National Trauma Research Action Plan (NTRAP) scoping review
Authors: Herrera-Escobar Juan P. , Osman Samia Y. , Das Sophiya , Toppo Alexander , Orlas Claudia P. , Castillo-Angeles Manuel , Rosario Angel , Janjua Mahin B. , Arain Muhammad Abdullah , Reidy Emma , Jarman Molly P. , Nehra Deepika , Price Michelle A. , Bulger Eileen M. , Haider Adil H. ,   the National Trauma Research Action Plan (NTRAP) Investigators Group
Published: February 2021

BACKGROUND

The aim of this scoping review is to identify and summarize patient-reported outcome measures (PROMs) that are being used to track long-term patient-reported outcomes (PROs) after injury and can potentially be included in trauma registries.

METHODS

Online databases were used to identify studies published between 2013 and 2019, from which we selected 747 articles that involved survivors of acute physical traumatic injury aged 18 years or older at time of injury and used PROMs to evaluate recovery between 6 months and 10 years postinjury. Data were extracted and summarized using descriptive statistics and a narrative synthesis of the results.

RESULTS

Most studies were observational, with relatively small sample sizes, and predominantly on traumatic brain injury or orthopedic patients. The number of PROs assessed per study varied from one to 12, for a total of 2052 PROs extracted, yielding 74 unique constructs (physical health, 25 [34%]; mental health, 27 [37%]; social health, 12 [16%]; cognitive health, 7 [10%]; and quality of life, 3 [4%]). These 74 constructs were assessed using 355 different PROMs. Mental health was the most frequently examined outcome domain followed by physical health. Health-related quality of life, which appeared in more than half of the studies (n = 401), was the most common PRO evaluated, followed by depressive symptoms. Physical health was the domain with the highest number of PROMs used (n = 157), and lower-extremity functionality was the PRO that contributed most PROMs (n = 33).

CONCLUSION

We identified a wide variety of PROMs available to track long-term PROs after injury in five different health domains: physical, mental, social, cognitive, and quality of life. However, efforts to fully understand the health outcomes of trauma patients remain inconsistent and insufficient. Defining PROs that should be prioritized and standardizing the PROMs to measure them will facilitate the incorporation of long-term outcomes in national registries to improve research and quality of care.

LEVEL OF EVIDENCE

Systematic Reviews & Meta-analyses, Level IV
Risk factors for abdominal surgical site infection after exploratory laparotomy among combat casualties
Authors: Bozzay Joseph D. , Walker Patrick F. , Schechtman David W. , Shaikh Faraz , Stewart Laveta , Carson M. Leigh , Tribble David R. , Rodriguez Carlos J. , Bradley Matthew J. ,   on behalf of the Infectious Disease Clinical Research Program Trauma Infectious Disease Outcomes Study Group
Published: February 2021

BACKGROUND

Surgical site infections (SSIs) are well-recognized complications after exploratory laparotomy for abdominal trauma; however, little is known about SSI development after exploration for battlefield abdominal trauma. We examined SSI risk factors after exploratory laparotomy among combat casualties.

METHODS

Military personnel with combat injuries sustained in Iraq and Afghanistan (June 2009 to May 2014) who underwent laparotomy and were evacuated to participating US military hospitals were included. Log-binominal regression was used to identify SSI risk factors.

RESULTS

Of 4,304 combat casualties, 341 patients underwent a total of 1,053 laparotomies. Abdominal SSIs were diagnosed in 49 patients (14.4%): 8% with organ space SSI, 4% with deep incisional SSI, and 4% with superficial SSIs (4 patients had multiple SSIs). Patients with SSIs had more colorectal (p < 0.001), small bowel (p = 0.010), duodenum (p = 0.006), pancreas (p = 0.032), and abdominal vascular injuries (p = 0.040), as well as prolonged open abdomen (p = 0.004) and more infections diagnosed before the SSI (or final exploratory laparotomy) versus non-SSI patients (p < 0.001). Sustaining colorectal injuries (risk ratio [RR], 3.20; 95% confidence interval [CI], 1.58–6.45), duodenum injuries (RR, 6.71; 95% CI, 1.73–25.58), and being diagnosed with prior infections (RR, 10.34; 95% CI, 5.05–21.10) were independently associated with any SSI development. For either organ space or deep incisional SSIs, non–intra-abdominal infections, fecal diversion, and duodenum injuries were independently associated, while being injured via an improvised explosive device was associated with reduced likelihood compared with penetrating nonblast (e.g., gunshot wounds) injuries. Non–intra-abdominal infections and hypotension were independently associated with organ space SSIs development alone, while sustaining blast injuries were associated with reduced likelihood.

CONCLUSION

Despite severity of injuries and the battlefield environment, the combat casualty laparotomy SSI rate is relatively low at 14%, with similar risk factors and rates reported following severe civilian trauma.

LEVEL OF EVIDENCE

Epidemiological, level III.
A comprehensive analysis of undertriage in a mature trauma system using geospatial mapping
Authors: Maish George , Horst Michael , Ting Brown Catherine , Morgan Madison , Bradburn Eric , Cook Alan , Rogers Frederick B.
Published: February 2021

INTRODUCTION

The correct triage of trauma patients to trauma centers (TCs) is essential. We sought to determine the percentage of patients who were undertriaged within the Pennsylvania (PA) trauma system and spatially analyze areas of undertriage (UTR) in PA for all age groups: pediatric, adult, and geriatric. We hypothesized that there would be certain areas that had high UTR for all age groups.

METHODS

From 2003 to 2015, all admissions from the Pennsylvania Trauma Systems Foundation registry and those meeting trauma criteria (International Classification of Diseases, Ninth Diseases: 800–959) from the Pennsylvania Health Care Cost Containment Council (PHC4) database were included. Admissions were divided into age groups: pediatric (<15 years), adult (15–64 years), and geriatric (≥65 years). All pediatric trauma cases were included from the Pennsylvania Trauma Systems Foundation and PHC4 registry, while only cases with Injury Severity Score of >9 were included in adult and geriatric age groups. Undertriage was defined as patients not admitted to level I/II adult TCs (n = 24), pediatric (n = 3), or adult and pediatric combined facility (n = 3) divided by the total number of patients from the PHC4 database. ArcGIS Desktop (version 10.7; ESRI, Redlands, CA) and GeoDa (version 1.14.0; CSDS, Chicago, IL) open source license were used for geospatial mapping of UTR with a spatial empirical Bayesian smoothed UTR by zip code tabulation area (ZCTA) and Stata (version 16.1; Stata Corp., College Station, TX) for statistical analyses.

RESULTS

There were significant percentages of UTR for all age groups. One area of high UTR for all age groups had TCs and large nontrauma centers in close proximity. There were high rates of UTR for all ages in rural areas, specifically in the upper central regions of PA, with limited access to TCs.

CONCLUSION

It appears there are two patterns leading to UTR. The first is in areas where TCs are in close proximity to large competing nontrauma centers, which may lead to inappropriate triage. The second has to do with lack of access to TCs. Geospatial mapping is a valuable tool that can be used to ascertain where trauma systems should focus scarce resources to decrease UTR.

LEVEL OF EVIDENCE

Epidemiological, level III; Care management, level III.
Frail geriatric patients with acute calculous cholecystitis: Operative versus nonoperative management?
Authors: Asmar Samer , Bible Letitia , Obaid Omar , Anand Tanya , Chehab Mohamad , Ditillo Michael , Castanon Lourdes , Nelson Adam , Joseph Bellal
Published: February 2021

INTRODUCTION

Nonoperative management of acute calculous cholecystitis (ACC) in the frail geriatric population is underexplored. The aim of our study was to examine long-term outcomes of frail geriatric patients with ACC treated with cholecystectomy compared with initial nonoperative management.

METHODS

We conducted a 2017 analysis of the Nationwide Readmissions Database and included frail geriatric (≥65 years) patients with ACC. Frailty was assessed using the five-factor modified frailty index. Patients were stratified into those undergoing cholecystectomy at index admission (operative management [OP]) versus those managed with nonoperative intervention (nonoperative management [NOP]). The NOP group was further subdivided into those who received antibiotics only and those who received percutaneous drainage. Primary outcomes were procedure-related complications in the OP group and 6-month failure of NOP (readmission with cholecystitis). Secondary outcomes were mortality and overall hospital length of stay.

RESULTS

A total of 53,412 geriatric patients with ACC were identified, 51.0% of whom were frail: 16,791 (61.6%) in OP group and 10,472 (38.4%) in NOP group (3,256 had percutaneous drainage, 7,216 received antibiotics only). Patients were comparable in age (76 ± 7 vs. 77 ± 8 years; p = 0.082) and modified frailty index (0.47 vs. 0.48; p = 0.132). Procedure-related complications in the OP group were 9.3%, and 6-month failure of NOP was 18.9%. Median time to failure of NOP management was 36 days (range, 12–78 days). Mortality was higher in the frail NOP group (5.2 vs. 3.2%; p < 0.001). The NOP group had more days of hospitalization (8 [4–15] vs. 5 [3–10]; p < 0.001). Both receiving antibiotics only (odds ratio, 1.6 [1.3–2.0]; p < 0.001) and receiving percutaneous drainage (odds ratio, 1.9 [1.7–2.2]; p < 0.001) were independently associated with increased mortality.

CONCLUSION

One in five patients failed NOP and subsequently had complicated hospital stays. Nonoperative management of frail elderly ACC patients may be associated with significant morbidity and mortality.

LEVEL OF EVIDENCE

Therapeutic, level IV.
The impact of prehospital TXA on mortality among bleeding trauma patients: A systematic review and meta-analysis
Authors: Almuwallad Ateeq , Cole Elaine , Ross Jennifer , Perkins Zane , Davenport Ross
Published: February 2021

BACKGROUND

Tranexamic acid (TXA) is an antifibrinolytic drug associated with improved survival among trauma patients with hemorrhage. Tranexamic acid is considered a primary hemostatic intervention in prehospital for treatment of bleeding alongside blood product transfusion.

METHODS

A systematic review and meta-analysis was conducted to investigate the impact of prehospital TXA on mortality among trauma patients with bleeding. A systematic search was conducted using the National Institute for Health and Care Excellence Healthcare Databases Advanced Search library which contain the following of databases: EMBASE, Medline, PubMed, BNI, EMCARE, and HMIC. Other databases searched included SCOPUS and the Cochrane Central Register for Clinical Trials Library. Quality assessment tools were applied among included studies; Cochrane Risk of Bias for randomized control trials and Newcastle-Ottawa Scale for cohort observational studies.

RESULTS

A total of 797 publications were identified from the initial database search. After removing duplicates and applying inclusion/exclusion criteria, four studies were included in the review and meta-analysis which identified a significant survival benefit in patients who received prehospital TXA versus no TXA. Three observational cohort and one randomized control trial were included into the review with a total of 2,347 patients (TXA, 1,169 vs. no TXA, 1,178). There was a significant reduction in 24 hours mortality; odds ratio (OR) of 0.60 (95% confidence interval [CI], 0.37–0.99). No statistical significant differences in 28 days to 30 days mortality; OR of 0.69 (95% CI, 0.47–1.02), or venous thromboembolism OR of 1.49 (95% CI, 0.90–2.46) were found.

CONCLUSION

This review demonstrates that prehospital TXA is associated with significant reductions in the early (24 hour) mortality of trauma patients with suspected or confirmed hemorrhage but no increase in the incidence of venous thromboembolism.

LEVEL OF EVIDENCE

Systematic review and meta-analysis. Level I
Crossmatch, Donor-specific Antibody Testing, and Immunosuppression in Simultaneous Liver and Kidney Transplantation: A Review
Authors: Das Anushka , Taner Timucin , Kim Jim , Emamaullee Juliet
Published: February 2021

Since the introduction of simultaneous liver-kidney transplantation (SLKT) in the 1960s, the potential for immunological protection from the liver allograft to a simultaneously transplanted kidney has been recognized. Due to expanded indications and changes in allocation policies, there has been increased utilization of SLKT. Despite growing experience, a lack of consensus exists regarding the extent of the immunological privilege of the liver the role for donor-specific HLA antibody (DSA) and crossmatch testing, and appropriateness of modern immunosuppression protocols in SLKT recipients. This review provides a detailed analysis of SLKT outcomes in the context of these factors, suggesting that although the liver can reduce the incidence of antibody-mediated rejection, attention should be given to liver allograft function, previous failed transplants, and other risk factors in pretransplant risk assessment. Current methods of DSA and crossmatch testing in SLKT are also discussed, and the role of specific DSA (high mean fluorescence intensity antibody, C1q+ binding) and their potential importance in posttransplant risk assessment are examined. Finally, trends in SLKT immunosuppression are discussed, including the use of nondepleting agents for induction and de-escalating use of steroids for maintenance immunosuppression. Ongoing research, including multicenter or randomized trials, will be necessary to optimize immune-related outcomes in SLKT recipients.
Cycle Thresholds Among Solid Organ Transplant Recipients Testing Positive for SARS-CoV-2
Authors: Theodore Deborah A. , Greendyke William G. , Miko Benjamin , Whittier Susan , Green Daniel A. , Shoucri Sherif , Verna Elizabeth C. , Zucker Jason , Sobieszczyk Magdalena E. , Aaron Justin G. , Scully Brian E. , Saiman Lisa , Pereira Marcus , Furuya E. Yoko
Published: February 2021

Background.

The optimal duration of transmission-based precautions among immunocompromised patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown.

Methods.

Retrospective review of patients with solid organ transplant with positive SARS-CoV-2 polymerase chain reaction result from nasopharyngeal specimens admitted to the hospital between March 13, 2020 and May 15, 2020.

Results.

Twenty-one percent of solid organ transplant recipients with positive SARS-CoV-2 polymerase chain reaction detected ≥20 d after symptom onset (or after first positive test among asymptomatic individuals) had a low cycle threshold (ie, high viral load). The majority of these patients were asymptomatic or symptomatically improved.

Conclusions.

Solid organ transplant recipients may have prolonged high viral burden of SARS-CoV-2. Further data are needed to understand whether cycle threshold data can help inform strategies for prevention of healthcare-associated transmission of SARS-CoV-2 and for appropriate discontinuation of transmission-based precautions.
Controlled DCD Liver Transplantation Is Not Associated With Increased Hyperfibrinolysis and Blood Loss After Graft Reperfusion
Authors: Karangwa Shanice A. , Adelmeijer Jelle , Burgerhof Johannes G.M. , Lisman Ton , de Meijer Vincent E. , de Kleine Ruben H. , Reyntjens Koen M.E.M. , van den Berg Aad P. , Porte Robert J. , de Boer Marieke T.
Published: February 2021

Background.

The specific effect of donation after circulatory death (DCD) liver grafts on fibrinolysis, blood loss, and transfusion requirements after graft reperfusion is not well known. The aim of this study was to determine whether transplantation of controlled DCD livers is associated with an elevated risk of hyperfibrinolysis, increased blood loss, and higher transfusion requirements upon graft reperfusion, compared with livers donated after brain death (DBD).

Methods.

A retrospective single-center analysis of all adult recipients of primary liver transplantation between 2000 and 2019 was performed (total cohort n = 628). Propensity score matching was used to balance baseline characteristics for DCD and DBD liver recipients (propensity score matching cohort n = 218). Intraoperative and postoperative hemostatic variables between DCD and DBD liver recipients were subsequently compared. Additionally, in vitro plasma analyses were performed to compare the intraoperative fibrinolytic state upon reperfusion.

Results.

No significant differences in median (interquartile range) postreperfusion blood loss (1.2 L [0.5–2.2] versus 1.3 L [0.6–2.2]; P = 0.62), red blood cell transfusion (2 units [0–4] versus 1.1 units [0–3]; P = 0.21), or fresh frozen plasma transfusion requirements (0 unit [0–2.2] versus 0 unit [0–0.9]; P = 0.11) were seen in DCD compared with DBD recipients, respectively. Furthermore, plasma fibrinolytic potential was similar in both groups.

Conclusions.

Transplantation of controlled DCD liver grafts does not result in higher intraoperative blood loss or more transfusion requirements, compared with DBD liver transplantation. In accordance with this, no evidence for increased hyperfibrinolysis upon reperfusion in DCD compared with DBD liver grafts was found.
Cumulative Deficits Frailty Index Predicts Outcomes for Solid Organ Transplant Candidates
Authors: Varughese Rhea A. , Theou Olga , Li Yanhong , Huang Xiaojin , Chowdhury Noori , Famure Olusegun , Selzner Nazia , MacIver Jane , Mathur Sunita , Kim S. Joseph , Rockwood Kenneth , Singer Lianne G.
Published: February 2021

Background.

Despite comprehensive multidisciplinary candidacy assessments to determine appropriateness for solid organ transplantation, limitations persist in identifying candidates at risk of adverse outcomes. Frailty measures may help inform candidacy evaluation. Our main objective was to create a solid organ transplant frailty index (FI), using the cumulative deficits model, from data routinely collected during candidacy assessments. Secondary objectives included creating a social vulnerability index (SVI) from assessment data and evaluating associations between the FI and assessment, waitlist, and posttransplant outcomes.

Methods.

In this retrospective cohort study of solid organ transplant candidates from Toronto General Hospital, cumulative deficits FI and SVI were created from data collected during candidacy evaluations for consecutive kidney, heart, liver, and lung transplant candidates. Regression modeling measured associations between the FI and transplant listing, death or removal from the transplant waitlist, and survival after waitlist placement.

Results.

For 794 patients, 40 variable FI and 10 variable SVI were created (258 lung, 222 kidney, 201 liver, and 113 heart transplant candidates). The FI correlated with assessment outcomes; patients with medical contraindications (mean FI 0.35 ± 0.10) had higher FI scores than those listed (0.29 ± 0.09), P < 0.001. For listed patients, adjusted for age, sex, transplant type, and SVI, higher FI was associated with an increased risk of death (pretransplant or posttransplant) or delisting (hazard ratio 1.03 per 0.01 FI score, 95% confidence interval, 1.01-1.05, P = 0.01).

Conclusions.

A cumulative deficits FI can be derived from routine organ transplant candidacy evaluations and may identify candidates at higher risk of adverse outcomes.
Ex Situ Perfusion of Hearts Donated After Euthanasia: A Promising Contribution to Heart Transplantation
Authors: van Suylen Vincent , Bunnik Eline M. , Hagenaars Johanna A.M. , Ertugrul Imran A. , Bollen Jan A.M. , Mariani Massimo A. , Erasmus Michiel E.
Published: February 2021

Background.

Organ donation after euthanasia is performed in an increasing number of countries. In this donation after circulatory death procedure, it has not been possible to donate the heart. Recent literature, however, reports positive results of heart donation after circulatory death. Therefore, patients who donate organs following euthanasia might be suitable candidates for heart donation. We want to confirm this assumption by sharing the results of 2 cases of heart donation following euthanasia with ex situ subnormothermic heart preservation. Our aim is to raise awareness of the potential of heart donation following euthanasia for both clinical transplantation and research.

Methods.

The data of 2 consecutive heart donations following euthanasia were collected prospectively. Informed consent was obtained from the patients themselves for heart donation for research purposes. An acellular oxygenated subnormothermic machine perfusion strategy was used to preserve both donor hearts. Subsequently, the hearts were evaluated on a normothermic perfusion machine using a balloon in the left ventricle.

Results.

Heart donation following euthanasia was feasible without significant changes in existing retrieval protocols. Duration of machine perfusion preservation was 408 and 432 minutes, for heart 1 and 2, respectively. For heart 1, developed pressure (Pdev) was 119 mm Hg, maximal rate of pressure rise (dP/dtmax), and fall (dP/dtmin) were 1524 mm Hg/s and −1057 mm Hg/s, respectively. For heart 2, Pdev was 142 mm Hg, dP/dtmax was 1098 mm Hg/s, and dP/dtmin was −802 mm Hg/s.

Conclusions.

Hearts donated following euthanasia are highly valuable for research purposes and can have sufficient quality to be transplanted. With the implementation of ex situ heart perfusion, patients who are to donate their organs following euthanasia should also be able to donate their hearts. The complex combination of euthanasia and heart donation is ethically sound and surgically feasible and can contribute to shortening the heart transplant waiting list.
A Systematic Review of Seizure-Freedom Rates in Patients With Benign Epilepsy of Childhood With Centrotemporal Spikes Receiving Antiepileptic Drugs
Authors: Gerstl Lucia , Willimsky Eva , Rémi Constanze , Noachtar Soheyl , Borggräfe Ingo , Tacke Moritz
Published: February 2021

Objectives

The objective of this study was to evaluate seizure remission rates in patients with benign epilepsy of childhood with centrotemporal spikes (BECTS) receiving antiepileptic drugs.

Methods

PubMed and Web of Science were searched for studies on pharmacotherapy in patients with BECTS using free search terms or Medical Subject Headings. Only studies that used seizure-freedom rates as an indicator for pharmaceutical efficacy were considered. Different antiepileptic drugs were compared using the Fisher exact test for seizure-freedom rates.

Results

A total of 19 studies were included, 6 of them being randomized controlled trials. The randomized controlled trials included a total of 308 patients and covered sulthiame (n = 52), topiramate (n = 45), levetiracetam (n = 43), oxcarbazepine (n = 31), carbamazepine (n = 68), and clobazam (n = 18) as well as placebo (n = 35) and untreated control groups (n = 16). Treatment success rates were significantly higher in those children treated with sulthiame, levetiracetam, and clobazam compared with the children treated with carbamazepine, oxcarbazepine, or topiramate.

Conclusions

The available literature suggests the use of sulthiame, levetiracetam, or clobazam as first-line agents for the treatment of BECTS.
Fascicular Sixth Nerve Palsy as a Presenting Sign of Metastatic Ovarian Carcinoma
Authors: Rohani Niloufar , Mortensen Peter , Lee Andrew G.
Published: February 2021

The most common etiology of an isolated abducens nerve palsy in an older adult with vasculopathic risk factors is presumed microvascular ischemia. Because the diagnosis of microvascular ischemia in this setting would not alter patient management, there is debate as to whether further workup is warranted under these circumstances. In this report, we describe a fascicular sixth nerve palsy as the initial presenting sign of metastatic ovarian carcinoma, and we highlight the importance of considering additional workup in select cases of isolated abducens nerve palsies.
Melatonin Versus Chloral Hydrate for Sleep Electroencephalography Recording in Children: A Comparative Study Using Bispectral Index Monitoring Scores and Electroencephalographic Sleep Stages
Authors: Yilmaz Sanem , Simsek Erdem , Gazeteci Tekin Hande , Aktan Gul , Gokben Sarenur , Tekgul Hasan
Published: February 2021

Purpose:

To compare the effects of chloral hydrate and melatonin on sleep EEG recordings in children by using standard EEG sleep stages and the bispectral index scores (BIS).

Methods:

A total of 86 children were randomly assigned to two groups: (1) melatonin group (n = 43) and (2) chloral hydrate group (n = 43). BIS monitoring scores and sleep EEGs were recorded simultaneously. The effect of two drugs on sleep EEG recording was evaluated with sleep stages of EEG and BIS.

Results:

There was no statistically significant difference between the groups with regard to time to sleep onset and the need for a second drug (P = 0.432; P = 1.000). Eight patients (18.6%) in chloral hydrate group reported side effects while there were no reported side effects in the melatonin group (P = 0.006). Mean BIS values during EEG recordings were similar in both groups (59.72 ± 18.69 minutes and 66.17 ± 18.44 minutes, respectively, P = 1.000). The average time to achieve N2 sleep was 32.38 minutes in the chloral hydrate group and 43.25 minutes in the melatonin group (P < 0.001). Both “time spent in wakefulness” and “N1 sleep” were found to be significantly higher in the melatonin group (P < 0.001 and P = 0.005). BIS scores higher than 75 were found to be suggestive for wakefulness; 75 to 66 for N1, 65 to 46 for N2, and values lower than 46 were found to be indicative for N3 sleep with a good strength of agreement in weighted Kappa analysis (95% confidence interval; weighted Kappa = 0.67).

Conclusions:

Melatonin is reliable and at least as effective as chloral hydrate for sleep EEG acquisition in children.
COVID-19 Continuous-EEG Case Series: A Descriptive Study
Authors: Zafar Saman , Aydemir Seyhmus , Karceski Steve , Doria Joseph W. , Schaefer Candace , Swarnkar Rohit , Afra Pegah
Published: February 2021

Purpose:

Corona virus disease 2019 (COVID-19) refers to coronavirus disease secondary to SARS-CoV2 infection mainly affecting the human respiratory system. The SARS-CoV2 has been reported to have neurotropic and neuroinvasive features and neurological sequalae with wide range of reported neurological manifestations, including cerebrovascular disease, skeletal muscle injury, meningitis, encephalitis, and demyelination, as well as seizures and focal status epilepticus. In this case series, we analyzed the continuous video-EEGs of patients with COVID-19 infection to determine the presence of specific EEG features or epileptogenicity.

Methods:

All continuous video-EEG tracings done on SARS-CoV2–positive patients during a 2-week period from April 5, 2020, to April 19, 2020, were reviewed. The demographics, clinical characteristics, imaging, and EEG features were analyzed and presented.

Results:

Of 23 patients undergoing continuous video-EEG, 16 were COVID positive and were included. Continuous video-EEG monitoring was ordered for “altered mental status” in 11 of 16 patients and for “clinical seizure” in 5 of 16 patients. None of the patients had seizures or status epilepticus as a presenting symptom of COVID-19 infection. Instead, witnessed clinical seizures developed as results of COVID-19–related medical illness(es): anoxic brain injury, stroke/hemorrhage, lithium (Li) toxicity (because of kidney failure), hypertension, and renal disease. Three patients required therapeutic burst suppression because of focal nonconvulsive status epilepticus, status epilepticus/myoclonus secondary to anoxic injury from cardiac arrest, and one for sedation (and with concomitant EEG abnormalities secondary to Li toxicity).

Conclusions:

In this observational case series of 16 patients with COVID-19 who were monitored with continuous video-EEG, most patients experienced a nonspecific encephalopathy. Clinical seizures and electrographic status epilepticus were the second most commonly observed neurological problem.
Tracking Multisite Seizure Propagation Using Ictal High-Gamma Activity
Authors: Tobochnik Steven , Bateman Lisa M. , Akman Cigdem I. , Anbarasan Deepti , Bazil Carl W. , Bell Michelle , Choi Hyunmi , Feldstein Neil A. , Kent Paul F. , McBrian Danielle , McKhann Guy M. , Mendiratta Anil , Pack Alison M. , Sands Tristan T. , Sheth Sameer A. , Srinivasan Shraddha , Schevon Catherine A.
Published: February 2021

Purpose:

Spatial patterns of long-range seizure propagation in epileptic networks have not been well characterized. Here, we use ictal high-gamma activity (HGA) as a proxy of intense neuronal population firing to map the spatial evolution of seizure recruitment.

Methods:

Ictal HGA (80–150 Hz) was analyzed in 13 patients with 72 seizures recorded by stereotactic depth electrodes, using previously validated methods. Distinct spatial clusters of channels with the ictal high-gamma signature were identified, and seizure hubs were defined as stereotypically recruited nonoverlapping clusters. Clusters correlated with asynchronous seizure terminations to provide supportive evidence for independent seizure activity at these sites. The spatial overlap between seizure hubs and interictal ripples was compared.

Results:

Ictal HGA was detected in 71% of seizures and 10% of implanted contacts, enabling tracking of contiguous and noncontiguous seizure recruitment. Multiple seizure hubs were identified in 54% of cases, including 43% of patients thought preoperatively to have unifocal epilepsy. Noncontiguous recruitment was associated with asynchronous seizure termination (odds ratio = 19.7; p = 0.029). Interictal ripples demonstrated greater spatial overlap with ictal HGA in cases with single seizure hubs compared with those with multiple hubs (100% vs. 66% per patient; p = 0.03).

Conclusions:

Ictal HGA may serve as a useful adjunctive biomarker to distinguish contiguous seizure spread from propagation to remote seizure sites. High-gamma sites were found to cluster in stereotyped seizure hubs rather than being broadly distributed. Multiple hubs were common even in cases that were considered unifocal.
Therapeutic effect of Cerebrolysin on reducing impaired cerebral endothelial cell permeability
Authors: Teng Hua , Li Chao , Zhang Yi , Lu Mei , Chopp Michael , Zhang Zheng Gang , Melcher-Mourgas Melanie , Fleckenstein Burkhard
Published: February 2021

Cerebrolysin has been shown to promote neurovascular protection and repair in preclinical models of stroke and neural injury and is demonstrating promise for stroke and neural injury therapeutic application in the clinic. The effect of Cerebrolysin on the human cerebral endothelial cell function has not been investigated. Using an in-vitro cerebral endothelial cell permeability assay and western blot analyses of tight junction and proinflammatory and procoagulant proteins, the present study showed that tissue plasminogen activator (tPA) and fibrin substantially impaired human cerebral endothelial cell barrier function and increased permeability, which persisted for at least 24 h. western blot analysis revealed that tPA and fibrin significantly increased proinflammatory and procoagulation proteins of intercellular adhesion molecule 1, high mobility group box 1, tumor necrosis factor α and phosphorylated nuclear factor kappa B-p65, and significantly reduced tight junction proteins zonular 1, occludin and claudin. However, Cerebrolysin significantly diminished and reversed tPA- and fibrin-impaired endothelial cell permeability, which was associated with significant reductions of tPA- and fibrin-augmented proinflammatory and procoagulation proteins and significant elevations of tPA- and fibrin-decreased tight junction proteins. The beneficial effect of Cerebrolysin appears specific because cerebroprotein hydrolysate, with a distinct peptide composition, failed to show the reduction of tPA- and fibrin-impaired permeability. These data indicate that cererbrolysin has a therapeutic effect on tPA- and fibrin-impaired cerebral endothelial cell permeability by reducing proinflammatory and procoagulation proteins and by elevating tight junction proteins.
Region-specific dysregulation of endocannabinoid system in learned helplessness model of depression
Authors: Huang Weiyuan , Ke Yue , Chen Rongqing
Published: February 2021

Researches have indicated that the endocannabinoid system (ECS) plays a crucial role in pathophysiology of depressive disorder. However, both hypo- and hyperfunction of the ECS were reported in depressive patients or animal models of depression. We proposed that the dual functional changes of the ECS in depression might be due to its region-specific dysregulation. Therefore, we investigated the mRNA expression of genes coding for the components of the ECS in the key depression-associated brain regions of the mouse learned helplessness model of depression. We found that in the mPFC, mRNA of transient receptor potential vanilloid type 1 (TRPV1) was significantly decreased in learned helplessness-resilient mice, whereas diacylglycerol lipases-α (DAGL-α) was decreased in both learned helplessness and learned helplessness-resilient mice. In the hippocampus, a significant increase of DAGL-α was observed in learned helplessness-resilient mice. In the amygdala, G-protein-coupled receptor 55 (GPR55) and DAGL-α were significantly decreased in both learned helplessness and learned helplessness-resilient mice. Meanwhile, fatty acid amide hydrolase (FAAH) was significantly decreased only in learned helplessness-resilient mice. In the LHb, the GPR55 was significantly decreased in both learned helplessness and learned helplessness-resilient mice, whereas the DAGL-β and FAAH were significantly downregulated only in learned helplessness-resilient mice. Therefore, our study reveals novel implications of the ECS in the development of depression-like or depression-resilient behaviors and discloses a region-specific manner of the ECS dysregulation by learned helplessness stress, suggesting that brain region-specific strategy might be necessary for the ECS to be intervened for the precise treatment of depression.
Bowel Emptying Methods Used by German Residents Living With Spina Bifida
Authors: Faleiros Fabiana , Santos Lilka Marques , Bimbatti Karina , Käppler Christoph
Published: February 2021

PURPOSE:

The purpose of this study was to describe and analyze methods of bowel emptying among Germans living with spina bifida. We also analyzed relationships between age, sex, level of spinal bifida anomaly, and methods of bowel elimination.

DESIGN:

A quantitative, descriptive study.

SUBJECTS AND SETTING:

The sample comprised 88 persons (56 women and 32 men) residing anywhere in the Federal Republic of Germany. Their mean age was 17.5 years (SD 13.64 years), range 0 to 55 years.

METHODS:

Data were collected through an online survey questionnaire developed for the urological follow-up protocol for patients with spina bifida. Parents completed the questionnaire for participants younger than 18 years.

RESULTS:

Twenty participants (22.7%) reported normal defecation and 68 (77.3%) reported neurogenic bowel dysfunction requiring regular bowel management. Participants requiring bowel management predominately used rectal irrigation (40.9%) and digital rectal stimulation (27.3%) to enhance bowel evacuation. Age emerged as the only factor related to the bowel management techniques. Younger participants (≤20 years) were more likely to use rectal irrigation for bowel evacuation (P = .001, Fisher's exact test), whereas older respondents (≥21 years) were more likely to use digital rectal stimulation (P = .015, Fisher's exact test). Analysis revealed no differences in methods of bowel evacuation based on sex or level of spina bifida anomaly (cervical, thoracic, lumbar, or sacral).

CONCLUSIONS:

Rectal irrigation was the most common method for bowel evacuation. Participants were less likely to employ potentially effective and more conservative measures for intestinal emptying, such as toilet training/timed evacuation associated with Valsalva maneuvers, abdominal press, abdominal massage, and digital rectal stimulation. Additional comparative studies with more participants and other countries with intestinal emptying methods are needed to better understand the needs of individuals with spina bifida and their families and to improve the health-related quality of life of these people.
A Pilot Study of Switching Electroconvulsive Therapy for Patients With Treatment Resistant Schizophrenia or Mood Disorder
Authors: Tan Xiao Wei , Oon Li Keat , Tsang Yun Ying Tammy , Ong Hatta Santoso , Tor Phern Chern
Published: February 2021

Objectives

Switching of ECT electrode modality is commonly done in clinical practice but outcomes are unclear. We aimed to compare the clinical outcomes between ECT modality switchers and nonswitchers in a large tertiary psychiatric institution over 1 year.

Methods

Brief Psychiatric Rating Scale (BPRS), Montgomery–Åsberg Depression Rating Scale (MADRS) and Montreal Cognitive Assessment (MoCA) were used to assess symptoms and cognition. General linear regression was utilized to compare the change of BPRS or MADRS and MoCA score among switchers vs nonswitchers.

Results

21.5% of 209 patients switched ECT. Baseline BPRS scores were lower among nonswitchers. Response rate in schizophrenia, depression and mania were higher for nonswitchers (69.6%, 81.35% and 84.8% respectively / 9.2 (SD 3.3) sessions) compared to switchers (53.8%, 0% and 66.7% respectively / 10.6 (SD 4.5) sessions). Most common ECT switches were Bifrontal (BF) to Bitemporal (BT) (schizophrenia), UB RUL (ultrabrief right unilateral) to BT (depression), and UB RUL to BT / BF (mania). There was no significant difference in the change of BPRS and MoCA scores between nonswitchers and switchers. However, there was significantly more improvement of MADRS scores among nonswitchers [adjusted mean ± SE: (−26.4 ± 2.8)] compared with switchers (−10.6) ±6.6).

Conclusions

ECT switching was commonly done and may result in better or worse outcomes than not switching depending on diagnosis. Controlled trials are required to address this urgent clinical issue.
Safe Administration of ECT in a Suicidal Patient With a Space-Occupying Astrocytoma
Authors: Youssef Nagy A. , Casola Benjamin , Rosenquist Peter B. , McCall William V. , Spearman Vanessa
Published: February 2021

Electroconvulsive therapy (ECT) can be lifesaving for patients suffering from treatment-resistant psychiatric conditions, especially acute suicidality or depression. However, space-occupying lesions pose risks associated with ECT use due in part to seizure-induced escalations in blood pressure with corresponding increases in cerebral blood flow and possibly intracranial pressure, subsequently increasing the risk of brain herniation. Here, we present the case of a patient with a left medial temporal lobe astrocytoma, worsening epileptic seizures, and nonepileptic seizures who underwent ECT for major depressive disorder and suicidality. The patient had improvement of depressive symptoms, resolution of suicidality, and brief cessation of nonepileptic seizures. Brief anterograde amnesia contributed to the termination of treatment. This case adds to the growing literature about the feasibility of ECT treatment in cerebral lesions prone to changes in intracranial pressure, such as the usually cystic astrocytomas.
Chemical exchange saturation transfer for detection of antiretroviral drugs in brain tissue
Authors: Bade Aditya N. , Gendelman Howard E. , McMillan JoEllyn , Liu Yutong
Published: February 2021

Human immunodeficiency virus type-1 (HIV-1) antiretroviral drug (ARV) theranostics facilitates biodistribution and efficacy of therapies designed to target viral reservoirs. To this end, we have now deployed intrinsic drug chemical exchange saturation transfer (CEST) contrast to detect ARV distribution within the central nervous system (CNS).

Methods

CEST effects for lamivudine (3TC) and emtricitabine (FTC) were measured by asymmetric magnetization transfer ratio analyses in solutions. CEST magnetic resonance imaging (MRI) was performed on 3TC-treated mice with analysis made by Lorentzian fitting.

Results

CEST effects of 3TC and FTC hydroxyl and amino protons linearly correlated to drug concentrations. 3TC was successfully detected in brain sub-regions by MRI. The imaging results were validated by measurements of CNS drug concentrations.

Conclusion

CEST contrasts can be used to detect ARVs using MRI. Such detection can be used to assess spatial-temporal drug biodistribution. This is most notable within the CNS where drug biodistribution may be more limited with the final goal of better understanding ARV-associated efficacy and potential toxicity.
Insulin-like peptide receptor mediated signaling pathways orchestrate regulation of energy homeostasis in the Pacific oyster,Crassostrea gigas
Authors: Li Yongjing , Fu Huiru , Zhang Fuqiang , Ren Liting , Tian Jing , Li Qi , Liu Shikai
Published: February 2021

The involvement of insulin/insulin-like growth factor (IIS) signaling pathway in growth regulation of marine invertebrates remains largely unexplored. In this study, we used a fast-growing Pacific oyster (Crassostrea gigas) variety “Haida No.1” as material to unravel the role of IIS system in growth regulation in oysters. Systematic bioinformatics analyses allowed to identify major components of IIS signaling pathway and insulin-like peptide receptor (ILPR) mediated signaling pathways, including PI3K-AKT, RAS-MAPK, and TOR, inC. gigas. Expression levels of the major genes in IIS and its downstream signaling pathways were significantly higher in “Haida No.1” than wild oysters, suggesting their involvement in growth regulation ofC. gigas. Expression profiles of IIS and its downstream signaling pathway genes were significantly altered by nutrient abundance and culture temperature. These results suggested that IIS signaling pathway coupled with the ILPR mediated signaling pathways orchestrated energy homeostasis to regulate growth in the Pacific oyster.

Research Highlights

ILPR, IRS, IGFBPRP,andIGFALSgenes were characterized in theC. gigas.

Major genes of IIS signaling pathway were highly expressed in fast-growingC. gigas.

IIS and downstream pathways participates in energy homeostasis of oysters.

ILPR mediated signaling pathways orchestrate growth regulation in oysters.
IHRW: An Improved Hypergraph Random Walk Model for Predicting Three-Drug Therapy
Authors: Wang Qi , Yan Guiying
Published: February 2021

Drug combination therapy is a well-established concept in the treatment of complex diseases due to its fewer side effects, lower toxicity, and better efficacy. However, it is challenging to identify efficacious drug combinations from many drug candidates. Computational models could greatly reduce the cost, but most models did not use data for more than two-drug combinations and could not predict three-drug therapy. However, three-drug combinations account for about 21% of the known combinations, which is a very important type of treatment. Here, we utilized higher-order information and developed an improved hypergraph random walk model (IHRW) for three-drug therapy prediction. This is the first method to explore the combination of three drugs.

As a result, the case studies of breast cancer, lung cancer, and colon cancer showed that IHRW had a powerful ability to predict potential efficacious three-drug combinations, which provides new prospects for complex disease treatment. The code of IHRW is freely available athttps://github.com/wangqi27/IHRW.
Guest-host supramolecular assembly of injectable hydrogel fibers for cell encapsulation
Authors: Miller Beverly , Hansrisuk Audrey , Highley Christopher B. , Caliari Steven R.
Published: February 2021

The fibrous architecture of the extracellular matrix (ECM) is recognized as an integral regulator of cell function. However, there is an unmet need to develop mechanically robust biomaterials mimicking nanofibrous tissue topography that are also injectable to enable minimally invasive delivery. In this study we have developed a fibrous hydrogel composed of supramolecularly-assembled hyaluronic acid (HA) nanofibers that exhibits mechanical integrity, shear-thinning, rapid self-healing, and cytocompatibility. HA was modified with methacrylates to permit fiber photocrosslinking following electrospinning and either ‘guest’ adamantane or ‘host’ β-cyclodextrin groups to guide supramolecular fibrous hydrogel assembly. Analysis of fibrous hydrogel rheological properties showed that the mixed guest-host fibrous hydrogel was more mechanically robust (6.6 ± 2.0 kPa, storage modulus (G′)) than unmixed guest hydrogel fibers (1.0 ± 0.1 kPa, G′) or host hydrogel fibers (1.1 ± 0.1 kPa, G′) separately. The reversible nature of the guest-host supramolecular interactions also allowed for shear-thinning and self-healing behavior as demonstrated by cyclic deformation testing. Human mesenchymal stromal cells (hMSCs) encapsulated in fibrous hydrogels demonstrated satisfactory viability following injection and after seven days of culture (> 85%). Encapsulated hMSCs were more spread and elongated when cultured in viscoelastic guest-host hydrogels compared to non-fibrous elastic controls, with hMSCs also showing significantly decreased circularity in fibrous guest-host hydrogels compared to non-fibrous guest-host hydrogels. Together, these data highlight the potential of this injectable fibrous hydrogel platform for cell and tissue engineering applications requiring minimally invasive delivery.
Tracking cell lineages in 3D by incremental deep learning
Authors: Sugawara Ko , Cevrim Cagri , Averof Michalis
Published: February 2021

Deep learning is emerging as a powerful approach for bioimage analysis. Its use in cell tracking is limited by the scarcity of annotated data for the training of deep learning models. Moreover, annotation, training, prediction and proofreading currently lack a unified user interface. We present ELEPHANT, an interactive platform for 3D cell tracking that addresses these challenges by taking an incremental approach to deep learning. ELEPHANT provides an interface that seamlessly integrates cell track annotation, deep learning, prediction and proofreading. This enables users to implement cycles of incremental learning starting from a few annotated nuclei. Successive prediction-validation cycles enrich the training data, leading to rapid improvements in tracking performance. We test the software’s performance against state-of-the-art methods and track lineages spanning the entire course of leg regeneration in a crustacean over 1 week (504 timepoints). ELEPHANT yields accurate, fully-validated cell lineages with a modest investment in time and effort.