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Article: Organoid-based

Korwin-Mihavics, Bethany R / Dews, Emmett A / di Genova, Bruno Martorelli / Huston, Christopher D

bioRxiv : the preprint server for biology

2023

Abstract: Typical cancer cell-based culture systems cannot support the full life cycle ... ...

Abstract	Typical cancer cell-based culture systems cannot support the full life cycle of
Language	English
Publishing date	2023-09-29
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.09.29.560165
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Article ; Online: Modified Clavien-Dindo-Sink Classification System for operative complications in adult spine surgery.

Ridolfi, Dominic / Oyekan, Anthony A / Tang, Melissa Yunting / Chen, Stephen R / Como, Christopher J / Dalton, Jonathan / Gannon, Emmett J / Jackson, Keith L / Bible, Jesse E / Kowalski, Christopher / de Groot, S Joseph / Donaldson, William F / Lee, Joon Y / Shaw, Jeremy D

Journal of neurosurgery. Spine

2024 , Page(s) 1–5

Abstract: Objective: Currently there is no standardized mechanism to describe or compare complications in adult spine surgery. Thus, the purpose of the present study was to modify and validate the Clavien-Dindo-Sink complication classification system for ... ...

Abstract	Objective: Currently there is no standardized mechanism to describe or compare complications in adult spine surgery. Thus, the purpose of the present study was to modify and validate the Clavien-Dindo-Sink complication classification system for applications in spine surgery. Methods: The Clavien-Dindo-Sink complication classification system was evaluated and modified for spine surgery by four fellowship-trained spine surgeons using a consensus process. A distinct group of three fellowship-trained spine surgeons completed a randomized electronic survey grading 71 real-life clinical case scenarios. The survey was repeated 2 weeks after its initial completion. Fleiss' and Cohen's kappa (κ) statistics were used to evaluate interrater and intrarater reliabilities, respectively. Results: Overall, interobserver reliability during the first and second rounds of grading was excellent with a κ of 0.847 (95% CI 0.785-0.908) and 0.852 (95% CI 0.791-0.913), respectively. In the first round, interrater reliability ranged from good to excellent with a κ of 0.778 for grade I (95% CI 0.644-0.912), 0.698 for grade II (95% CI 0.564-0.832), 0.861 for grade III (95% CI 0.727-0.996), 0.845 for grade IV-A (95% CI 0.711-0.979), 0.962 for grade IV-B (95% CI 0.828-1.097), and 0.960 for grade V (95% CI 0.826-1.094). Intraobserver reliability testing for all three independent observers was excellent with a κ of 0.971 (95% CI 0.944-0.999) for rater 1, 0.963 (95% CI 0.926-1.001) for rater 2, and 0.926 (95% CI 0.869-0.982) for rater 3. Conclusions: The Modified Clavien-Dindo-Sink Classification System demonstrates excellent interrater and intrarater reliability in adult spine surgery cases. This system provides a useful framework to better communicate the severity of spine-related complications.
Language	English
Publishing date	2024-02-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	2158643-3
ISSN	1547-5646 ; 1547-5654
ISSN (online)	1547-5646
ISSN	1547-5654
DOI	10.3171/2023.11.SPINE23396
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Article: Use of L5-S1 transdiscal screws in the treatment of isthmic spondylolisthesis: a technical note.

Chen, Stephen R / Gibbs, Christopher M / Zheng, Aaron / Dalton, Jonathan F / Gannon, Emmett J / Shaw, Jeremy D / Ward, W Timothy / Lee, Joon Y

Journal of spine surgery (Hong Kong)

2022 Volume 7, Issue 4, Page(s) 510–515

Abstract: Surgical treatment of L5-S1 isthmic spondylolisthesis consists of a combination of decompression and fusion. One previously discussed mode of fusion is via transdiscal screws. Biomechanical studies of transdiscal screws have demonstrated greater rigidity ...

Abstract	Surgical treatment of L5-S1 isthmic spondylolisthesis consists of a combination of decompression and fusion. One previously discussed mode of fusion is via transdiscal screws. Biomechanical studies of transdiscal screws have demonstrated greater rigidity than traditional pedicle screw fixation, which theoretically translates to a higher fusion rate. Furthermore, when compared to pedicle screw fixation, transdiscal screw fixation also demonstrates improved functional and radiographic outcomes. However, transdiscal screw placement can be technically difficult. At this time, a detailed surgical technique has yet to be reported in the literature. Our surgical technique for transdiscal screw placement using intraoperative C-arm at L5-S1 is described. We include considerations for preoperative planning including necessary imaging and appropriate patient selection. We also discuss intraoperative concerns such as setup, surgical approach, proper screw trajectory, and our method for achieving indirect decompression. The results of thirteen consecutive patients treated with transdiscal screw fixation are described. One patient had subcutaneous seroma requiring reoperation (7.7%), three patients had implant failure (23.1%), and one patient had nonunion (7.7%). Our results suggest that transdiscal screw fixation is a safe and acceptable alternative for stabilization and indirect decompression of L5-S1 isthmic spondylolisthesis. Recent innovation in intraoperative navigation and robotic surgery may lessen the technical difficulty of transdiscal screw placement and make it even more effective.
Language	English
Publishing date	2022-01-31
Publishing country	China
Document type	Journal Article
ZDB-ID	2874556-5
ISSN	2414-4630 ; 2414-469X
ISSN (online)	2414-4630
ISSN	2414-469X
DOI	10.21037/jss-21-73
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Article ; Online: Constipation Predominant Irritable Bowel Syndrome and Functional Constipation Are Not Discrete Disorders: A Machine Learning Approach.

Ruffle, James K / Tinkler, Linda / Emmett, Christopher / Ford, Alexander C / Nachev, Parashkev / Aziz, Qasim / Farmer, Adam D / Yiannakou, Yan

The American journal of gastroenterology

2020 Volume 116, Issue 1, Page(s) 142–151

Abstract: Introduction: Chronic constipation is classified into 2 main syndromes, irritable bowel syndrome with constipation (IBS-C) and functional constipation (FC), on the assumption that they differ along multiple clinical characteristics and are plausibly of ... ...

Abstract	Introduction: Chronic constipation is classified into 2 main syndromes, irritable bowel syndrome with constipation (IBS-C) and functional constipation (FC), on the assumption that they differ along multiple clinical characteristics and are plausibly of distinct pathophysiology. Our aim was to test this assumption by applying machine learning to a large prospective cohort of comprehensively phenotyped patients with constipation. Methods: Demographics, validated symptom and quality of life questionnaires, clinical examination findings, stool transit, and diagnosis were collected in 768 patients with chronic constipation from a tertiary center. We used machine learning to compare the accuracy of diagnostic models for IBS-C and FC based on single differentiating features such as abdominal pain (a "unisymptomatic" model) vs multiple features encompassing a range of symptoms, examination findings and investigations (a "syndromic" model) to assess the grounds for the syndromic segregation of IBS-C and FC in a statistically formalized way. Results: Unisymptomatic models of abdominal pain distinguished between IBS-C and FC cohorts near perfectly (area under the curve 0.97). Syndromic models did not significantly increase diagnostic accuracy (P > 0.15). Furthermore, syndromic models from which abdominal pain was omitted performed at chance-level (area under the curve 0.56). Statistical clustering of clinical characteristics showed no structure relatable to diagnosis, but a syndromic segregation of 18 features differentiating patients by impact of constipation on daily life. Discussion: IBS-C and FC differ only about the presence of abdominal pain, arguably a self-fulfilling difference given that abdominal pain inherently distinguishes the 2 in current diagnostic criteria. This suggests that they are not distinct syndromes but a single syndrome varying along one clinical dimension. An alternative syndromic segregation is identified, which needs evaluation in community-based cohorts. These results have implications for patient recruitment into clinical trials, future disease classifications, and management guidelines.
MeSH term(s)	Abdominal Pain/physiopathology ; Adult ; Chronic Disease ; Cohort Studies ; Constipation/classification ; Constipation/physiopathology ; Cost of Illness ; Female ; Humans ; Irritable Bowel Syndrome/classification ; Irritable Bowel Syndrome/physiopathology ; Male ; Middle Aged ; Principal Component Analysis ; Supervised Machine Learning
Language	English
Publishing date	2020-08-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	390122-1
ISSN	1572-0241 ; 0002-9270
ISSN (online)	1572-0241
ISSN	0002-9270
DOI	10.14309/ajg.0000000000000816
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Article ; Online: Classical Complement Pathway Inhibition in a "Human-On-A-Chip" Model of Autoimmune Demyelinating Neuropathies.

Advanced therapeutics

2022 Volume 5, Issue 6

Abstract: Chronic autoimmune demyelinating neuropathies are a group of rare neuromuscular disorders with complex, poorly characterized etiology. Here we describe a phenotypic, human-on-a-chip (HoaC) electrical conduction model of two rare autoimmune demyelinating ... ...

Abstract	Chronic autoimmune demyelinating neuropathies are a group of rare neuromuscular disorders with complex, poorly characterized etiology. Here we describe a phenotypic, human-on-a-chip (HoaC) electrical conduction model of two rare autoimmune demyelinating neuropathies, chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN), and explore the efficacy of TNT005, a monoclonal antibody inhibitor of the classical complement pathway. Patient sera was shown to contain anti-GM1 IgM and IgG antibodies capable of binding to human primary Schwann cells and induced pluripotent stem cell derived motoneurons. Patient autoantibody binding was sufficient to activate the classical complement pathway resulting in detection of C3b and C5b-9 deposits. A HoaC model, using a microelectrode array with directed axonal outgrowth over the electrodes treated with patient sera, exhibited reductions in motoneuron action potential frequency and conduction velocity. TNT005 rescued the serum-induced complement deposition and functional deficits while treatment with an isotype control antibody had no rescue effect. These data indicate that complement activation by CIDP and MMN patient serum is sufficient to mimic neurophysiological features of each disease and that complement inhibition with TNT005 was sufficient to rescue these pathological effects and provide efficacy data included in an investigational new drug application, demonstrating the model's translational potential.
Language	English
Publishing date	2022-04-05
Publishing country	Germany
Document type	Journal Article
ISSN	2366-3987
ISSN (online)	2366-3987
DOI	10.1002/adtp.202200030
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Article ; Online: Trans-anal irrigation therapy to treat adult chronic functional constipation: systematic review and meta-analysis.

Emmett, Christopher D / Close, Helen J / Yiannakou, Yan / Mason, James M

BMC gastroenterology

2015 Volume 15, Page(s) 139

Abstract: Background: Trans-anal irrigation (TAI) is used widely to treat bowel dysfunction, although evidence for its use in adult chronic functional constipation remains unclear. Long-term outcome data are lacking, and the effectiveness of therapy in this ... ...

Abstract	Background: Trans-anal irrigation (TAI) is used widely to treat bowel dysfunction, although evidence for its use in adult chronic functional constipation remains unclear. Long-term outcome data are lacking, and the effectiveness of therapy in this patient group is not definitively known. Methods: Evidence for effectiveness and safety was reviewed and the quality of studies was assessed. Primary research articles of patients with chronic functional constipation, treated with TAI as outpatients and published in English in indexed journals were eligible. Searching included major bibliographical databases and search terms: bowel dysfunction, defecation, constipation and irrigation. Fixed- and random-effect meta-analyses were performed. Results: Seven eligible uncontrolled studies, including 254 patients, of retrospective or prospective design were identified. The definition of treatment response varied and was investigator-determined. The fixed-effect pooled response rate (the proportion of patients with a positive outcome based on investigator-reported response for each study) was 50.4 % (95 % CI: 44.3-56.5 %) but featured substantial heterogeneity (I(2) = 67.1 %). A random-effects estimate was similar: 50.9 % (95 % CI: 39.4-62.3 %). Adverse events were inconsistently reported but were commonplace and minor. Conclusions: The reported success rate of irrigation for functional constipation is about 50 %, comparable to or better than the response seen in trials of pharmacological therapies. TAI is a safe treatment benefitting some patients with functional constipation, which is a chronic refractory condition. However findings for TAI vary, possibly due to varying methodology and context. Well-designed prospective trials are required to improve the current weak evidence base.
MeSH term(s)	Adult ; Anal Canal ; Chronic Disease ; Constipation/therapy ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; Retrospective Studies ; Therapeutic Irrigation/methods ; Therapeutic Irrigation/statistics & numerical data ; Treatment Outcome
Language	English
Publishing date	2015-10-16
Publishing country	England
Document type	Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't ; Review ; Systematic Review
ZDB-ID	2041351-8
ISSN	1471-230X ; 1471-230X
ISSN (online)	1471-230X
ISSN	1471-230X
DOI	10.1186/s12876-015-0354-7
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Article ; Online: Recurrent Pulmonary Artery Interventions Following the Norwood Procedure Are Not Associated With Conduit Type.

Spigel, Zachary A / Kalustian, Alyssa B / Binsalamah, Ziyad M / Caldarone, Christopher A / Imamura, Michiaki / Adachi, Iki / Heinle, Jeffrey S / McKenzie, Emmett D

Seminars in thoracic and cardiovascular surgery

2020 Volume 33, Issue 1, Page(s) 195–201

Abstract: Given pulmonary artery interventions following the Norwood procedure can recur, the average number of occurrences per patient over time is likely more informative than the crude percentage of patients who required an intervention. Pulmonary artery ... ...

Abstract	Given pulmonary artery interventions following the Norwood procedure can recur, the average number of occurrences per patient over time is likely more informative than the crude percentage of patients who required an intervention. Pulmonary artery intervention was defined as any surgical or catheter-based procedure after the Norwood procedure. The number of pulmonary artery interventions for patients with hypoplastic left heart syndrome were compared between patients with modified Blalock-Taussig Shunts (MBTS) and right ventricle-to-pulmonary artery conduits (RVPA) at a single institution from 2011 to 2018. The comparison was replicated using data from the Single Ventricle Reconstruction Trial (SVR), a nonoverlapping dataset. The mean number of pulmonary artery interventions per patient over time (mean cumulative function, MCF) is described using Nelson-Aalen estimates and compared using the pseudo-score test. The number of patients requiring intervention was compared using the chi-square test. Using our institutional dataset, the Norwood operation was performed on 117 patients (59 MBTS, 58 RVPA). In total, 73 patients had a pulmonary artery intervention, including 32 of 58 (55%) after MBTS and 41 of 59 (69%) after RVPA (P= 0.11). The MCF did not vary between cohorts (P = 0.55). Using the SVR trial dataset, 140 of 549 patients required pulmonary artery intervention, including 55 (21%) after MBTS and 85 (30%) after RVPA (P = 0.0090). The MCF did not vary between cohorts (P = 0.067). Although more patients with RVPA than MBTS require pulmonary artery interventions after the Norwood procedure, the MCFs are not different, which may be of greater importance to patients and families.
MeSH term(s)	Blalock-Taussig Procedure/adverse effects ; Heart Ventricles/surgery ; Humans ; Hypoplastic Left Heart Syndrome/diagnostic imaging ; Hypoplastic Left Heart Syndrome/surgery ; Norwood Procedures/adverse effects ; Pulmonary Artery/diagnostic imaging ; Pulmonary Artery/surgery ; Retrospective Studies ; Treatment Outcome
Language	English
Publishing date	2020-06-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	1038278-1
ISSN	1532-9488 ; 1043-0679
ISSN (online)	1532-9488
ISSN	1043-0679
DOI	10.1053/j.semtcvs.2020.05.028
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Article ; Online: Use of a Piglet Model for the Study of Anesthetic-induced Developmental Neurotoxicity (AIDN): A Translational Neuroscience Approach.

Whitaker, Emmett E / Zheng, Christopher Z / Bissonnette, Bruno / Miller, Andrew D / Koppert, Tanner L / Tobias, Joseph D / Pierson, Christopher R / Christofi, Fedias L

Journal of visualized experiments : JoVE

2017 , Issue 124

Abstract: Anesthesia cannot be avoided in many cases when surgery is required, particularly in children. Recent investigations in animals have raised concerns that anesthesia exposure may lead to neuronal apoptosis, known as anesthesia-induced developmental ... ...

Abstract	Anesthesia cannot be avoided in many cases when surgery is required, particularly in children. Recent investigations in animals have raised concerns that anesthesia exposure may lead to neuronal apoptosis, known as anesthesia-induced developmental neurotoxicity (AIDN). Furthermore, some clinical studies in children have suggested that anesthesia exposure may lead to neurodevelopmental deficits later in life. Nonetheless, an ideal animal model for preclinical study has yet to be developed. The neonatal piglet represents a valuable model for preclinical study, as they share a striking number of developmental similarities with humans. The anatomy and physiology of piglets allow for implementation of rigorous human perioperative conditions in both survival and non-survival procedures. Femoral artery catheterization allows for close monitoring, thus enabling prompt correction of any deviation of the piglet's vital signs and chemistries. In addition, there are multiple developmental similarities between piglets and human neonates. The techniques required to use piglets for experimentation will require experience to master. A pediatric anesthesiologist is a critical member of the investigative team. We describe, in a general sense, the appropriate use of a piglet model for neurodevelopmental study.
Language	English
Publishing date	2017-06-11
Publishing country	United States
Document type	Journal Article
ISSN	1940-087X
ISSN (online)	1940-087X
DOI	10.3791/55193
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Article: Long-term cattle grazing shifts the ecological state of forest soils.

Proesmans, Willem / Andrews, Christopher / Gray, Alan / Griffiths, Rob / Keith, Aidan / Nielsen, Uffe N / Spurgeon, David / Pywell, Richard / Emmett, Bridget / Vanbergen, Adam J

Ecology and evolution

2022 Volume 12, Issue 4, Page(s) e8786

Abstract: Cattle grazing profoundly affects abiotic and biotic characteristics of ecosystems. While most research has been performed on grasslands, the effect of large managed ungulates on forest ecosystems has largely been neglected. Compared to a baseline ... ...

Abstract	Cattle grazing profoundly affects abiotic and biotic characteristics of ecosystems. While most research has been performed on grasslands, the effect of large managed ungulates on forest ecosystems has largely been neglected. Compared to a baseline seminatural state, we investigated how long-term cattle grazing of birch forest patches affected the abiotic state and the ecological community (microbes and invertebrates) of the soil subsystem. Grazing strongly modified the soil abiotic environment by increasing phosphorus content, pH, and bulk density, while reducing the C:N ratio. The reduced C:N ratio was strongly associated with a lower microbial biomass, mainly caused by a reduction of fungal biomass. This was linked to a decrease in fungivorous nematode abundance and the nematode channel index, indicating a relative uplift in the importance of the bacterial energy-channel in the nematode assemblages. Cattle grazing highly modified invertebrate community composition producing distinct assemblages from the seminatural situation. Richness and abundance of microarthropods was consistently reduced by grazing (excepting collembolan richness) and grazing-associated changes in soil pH, Olsen P, and reduced soil pore volume (bulk density) limiting niche space and refuge from physical disturbance. Anecic earthworm species predominated in grazed patches, but were absent from ungrazed forest, and may benefit from manure inputs, while their deep vertical burrowing behavior protects them from physical disturbance. Perturbation of birch forest habitat by long-term ungulate grazing profoundly modified soil biodiversity, either directly through increased physical disturbance and manure input or indirectly by modifying soil abiotic conditions. Comparative analyses revealed the ecosystem engineering potential of large ungulate grazers in forest systems through major shifts in the composition and structure of microbial and invertebrate assemblages, including the potential for reduced energy flow through the fungal decomposition pathway. The precise consequences for species trophic interactions and biodiversity-ecosystem function relationships remain to be established, however.
Language	English
Publishing date	2022-03-31
Publishing country	England
Document type	Journal Article
ZDB-ID	2635675-2
ISSN	2045-7758
ISSN	2045-7758
DOI	10.1002/ece3.8786
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Article: Use of a piglet model for the study of anesthetic-induced developmental neurotoxicity (aidn): a translational neuroscience approach

Whitaker, Emmett E / Zheng, Christopher Z / Bissonnette, Bruno / Miller, Andrew D / Koppert, Tanner L / Tobias, Joseph D / Pierson, Christopher R / Christofi, Fedias L

Journal of visualized experiments. 2017 June 11, , no. 124

2017

Abstract	Anesthesia cannot be avoided in many cases when surgery is required, particularly in children. Recent investigations in animals have raised concerns that anesthesia exposure may lead to neuronal apoptosis, known as anesthesia-induced developmental neurotoxicity (AIDN). Furthermore, some clinical studies in children have suggested that anesthesia exposure may lead to neurodevelopmental deficits later in life. Nonetheless, an ideal animal model for preclinical study has yet to be developed. The neonatal piglet represents a valuable model for preclinical study, as they share a striking number of developmental similarities with humans. The anatomy and physiology of piglets allow for implementation of rigorous human perioperative conditions in both survival and non-survival procedures. Femoral artery catheterization allows for close monitoring, thus enabling prompt correction of any deviation of the piglet's vital signs and chemistries. In addition, there are multiple developmental similarities between piglets and human neonates. The techniques required to use piglets for experimentation will require experience to master. A pediatric anesthesiologist is a critical member of the investigative team. We describe, in a general sense, the appropriate use of a piglet model for neurodevelopmental study.
Keywords	anesthesia ; animal models ; apoptosis ; catheters ; children ; clinical trials ; humans ; monitoring ; neonates ; neurons ; neurophysiology ; neurotoxicity ; piglets ; surgery
Language	English
Dates of publication	2017-0611
Size	p. e55193.
Publishing place	Journal of Visualized Experiments
Document type	Article
ZDB-ID	2259946-0
ISSN	1940-087X
ISSN	1940-087X
DOI	10.3791/55193
Database	NAL-Catalogue (AGRICOLA)

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