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Article ; Online: Overcoming Operator-Generated False-Negative Results in SARS-CoV-2 Testing-Reply.

Higgins, Thomas S / Wu, Arthur W / Ting, Jonathan Y

JAMA otolaryngology-- head & neck surgery

2021 Volume 147, Issue 4, Page(s) 404–405

MeSH term(s)	COVID-19 ; COVID-19 Testing ; False Negative Reactions ; Humans ; SARS-CoV-2 ; Sensitivity and Specificity
Language	English
Publishing date	2021-02-18
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	2701825-8
ISSN	2168-619X ; 2168-6181
ISSN (online)	2168-619X
ISSN	2168-6181
DOI	10.1001/jamaoto.2020.5582
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Article ; Online: Surgical management and weight-bearing recommendations for geriatric distal femur fractures.

Haller, Justin M / Marchand, Lucas S / Higgins, Thomas F / O'Toole, Robert V / Reider, Lisa

OTA international : the open access journal of orthopaedic trauma

2023 Volume 7, Issue 1, Page(s) e296

Abstract: Objective: To investigate current practices among orthopaedic trauma surgeons in treating geriatric distal femur fractures and evaluate current postoperative weight-bearing recommendations.: Methods: A 26-question survey was emailed to Major ... ...

Abstract	Objective: To investigate current practices among orthopaedic trauma surgeons in treating geriatric distal femur fractures and evaluate current postoperative weight-bearing recommendations. Methods: A 26-question survey was emailed to Major Extremity Trauma Research Consortium surgeon members to characterize current practice with different fixation methods for distal femur fractures and the surgeon-directed postoperative weight-bearing recommendations for each approach. Results: Surveys were completed by 123 orthopaedic trauma surgeons with a response rate of 37% (123/332). Retrograde intramedullary nailing (IMN) was commonly performed by 88% of surgeons, and lateral locked plate was commonly performed by 74% of surgeons. Retrograde IMN with a lateral plate was commonly performed by 51% of surgeons. Dual femoral plating was commonly performed by 18% of surgeons and sometimes performed by 39% of surgeons. Surgeons were significantly more likely to allow immediate postoperative weight-bearing for retrograde IMN ( Conclusion: A variety of implants are commonly used to treat geriatric distal femur fractures. Patients with distal femur fracture commonly have weight-bearing restrictions in the immediate postoperative period. A large proportion of orthopaedic trauma surgeons have clinical equipoise for an RCT to investigate the impact of surgical construct and weight-bearing on geriatric distal femur fracture patient recovery.
Language	English
Publishing date	2023-12-14
Publishing country	United States
Document type	Journal Article
ISSN	2574-2167
ISSN (online)	2574-2167
DOI	10.1097/OI9.0000000000000296
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Article ; Online: Greater Acute Articular Inflammatory Response in Tibial Plafond Fractures as Compared to Ankle Fractures.

Marchand, Lucas S / Rothberg, David L / Higgins, Thomas F / Haller, Justin M

Foot & ankle international

2022 Volume 43, Issue 11, Page(s) 1465–1473

Abstract: Background: Several factors are thought to contribute to posttraumatic osteoarthritis (PTOA) development, including the posttraumatic inflammatory response. The purpose of this study was to compare 2 injuries at the same joint with a different severity ... ...

Abstract	Background: Several factors are thought to contribute to posttraumatic osteoarthritis (PTOA) development, including the posttraumatic inflammatory response. The purpose of this study was to compare 2 injuries at the same joint with a different severity and prognosis. This study compared the intra-articular inflammatory response after rotational ankle fracture (lower energy and less PTOA) with tibial plafond fracture (higher energy and more PTOA). Methods: This prospective comparative study was conducted at a level 1 trauma center between 2014-2019. Patients between 18 and 60 years of age with acute ankle or tibial plafond fractures were enrolled. Patients with preexisting ankle OA, autoimmune disease, additional injury, or open fractures were excluded. Synovial fluid aspirations were obtained within 24 hours of injury. The concentrations of interleukin (IL)-1β, IL-1 receptor antagonist (IL-1RA), IL-6, IL-8, and IL-10 and matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 were quantified. Results: Aspiration were obtained from 29 plafond fractures and 36 ankle fractures. Mean age was 43 years, and patients were predominately female (64%). Age, gender, and comorbidities did not vary between cohorts. Of the plafond fractures, 13 were 43-B and 16 were 43-C injuries. Ankle fractures were predominately 44-B injuries, and 15 ankle fracture had articular impaction. IL-10, IL-1β, IL-6, IL-8, MMP-1, MMP-3, and MMP-13 were all significantly higher in acute plafond fractures as compared to acute ankle fractures. Conclusion: This study compared articular inflammatory marker profiles after fractures of different severities. Several cytokines were elevated in plafond fractures as compared to ankle fractures, suggesting a greater inflammatory response with plafond fractures. Given the difference in prognosis for and higher rate of PTOA after plafond fractures, these data strengthen the case that postinjury inflammatory response plays a role in PTOA development. Given that the postinjury inflammatory response is one of the few modifiable variables of these injuries, future research in this area remains important. Level of evidence: Level II, prospective.
MeSH term(s)	Adult ; Female ; Humans ; Ankle Fractures ; Interleukin-10 ; Interleukin-6 ; Interleukin-8 ; Matrix Metalloproteinase 13 ; Matrix Metalloproteinase 3 ; Osteoarthritis ; Prospective Studies ; Tibial Fractures ; Male
Chemical Substances	Interleukin-10 (130068-27-8) ; Interleukin-6 ; Interleukin-8 ; Matrix Metalloproteinase 13 (EC 3.4.24.-) ; Matrix Metalloproteinase 3 (EC 3.4.24.17)
Language	English
Publishing date	2022-09-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	1183283-6
ISSN	1944-7876 ; 1071-1007
ISSN (online)	1944-7876
ISSN	1071-1007
DOI	10.1177/10711007221119111
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Zs.A 1600: Show issues

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Article ; Online: Reply: When Will We Stop Debating on the Value of TEE in CABG?

Metkus, Thomas S / Grant, Michael C / Zwischenberger, Brittany / Higgins, Robert

Journal of the American College of Cardiology

2021 Volume 78, Issue 17, Page(s) e139–e140

MeSH term(s)	Coronary Artery Bypass ; Echocardiography, Transesophageal ; Humans
Language	English
Publishing date	2021-10-21
Publishing country	United States
Document type	Letter ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S. ; Comment
ZDB-ID	605507-2
ISSN	1558-3597 ; 0735-1097
ISSN (online)	1558-3597
ISSN	0735-1097
DOI	10.1016/j.jacc.2021.08.032
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Zs.A 1846: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 196: Show issues

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Article ; Online: Alterations in sperm RNAs persist after alcohol cessation and correlate with epididymal mitochondrial dysfunction.

Roach, Alexis N / Bhadsavle, Sanat S / Higgins, Samantha L / Derrico, Destani D / Basel, Alison / Thomas, Kara N / Golding, Michael C

Andrology

2023

Abstract: Background: Chronic preconception paternal alcohol use adversely modifies the sperm epigenome, inducing fetoplacental and craniofacial growth defects in the offspring of exposed males. A crucial outstanding question in the field of paternal epigenetic ... ...

Abstract	Background: Chronic preconception paternal alcohol use adversely modifies the sperm epigenome, inducing fetoplacental and craniofacial growth defects in the offspring of exposed males. A crucial outstanding question in the field of paternal epigenetic inheritance concerns the resilience of the male germline and its capacity to recover and correct sperm-inherited epigenetic errors after stressor withdrawal. Objectives: We set out to determine if measures of the sperm-inherited epigenetic program revert to match the control treatment 1 month after withdrawing the daily alcohol treatments. Materials and methods: Using a voluntary access model, we exposed C57BL/6J males to 6% or 10% alcohol for 10 weeks, withdrew the alcohol treatments for 4 weeks, and used RNA sequencing to examine gene expression patterns in the caput section of the epididymis. We then compared the abundance of sperm small RNA species between treatments. Results: In the caput section of the epididymis, chronic alcohol exposure induced changes in the transcriptional control of genetic pathways related to the mitochondrial function, oxidative phosphorylation, and the generalized stress response (EIF2 signaling). Subsequent analysis identified region-specific, alcohol-induced changes in mitochondrial DNA copy number across the epididymis, which correlated with increases in the mitochondrial DNA content of alcohol-exposed sperm. Notably, in the corpus section of the epididymis, increases in mitochondrial DNA copy number persisted 1 month after alcohol cessation. Analysis of sperm noncoding RNAs between control and alcohol-exposed males 1 month after alcohol withdrawal revealed a ∼100-fold increase in mir-196a, a microRNA induced as part of the nuclear factor erythroid 2-related factor 2 (Nrf2)-driven cellular antioxidant response. Discussion and conclusion: Our data reveal that alcohol-induced epididymal mitochondrial dysfunction and differences in sperm noncoding RNA content persist after alcohol withdrawal. Further, differences in mir-196a and sperm mitochondrial DNA copy number may serve as viable biomarkers of adverse alterations in the sperm-inherited epigenetic program.
Language	English
Publishing date	2023-12-03
Publishing country	England
Document type	Journal Article
ZDB-ID	2696108-8
ISSN	2047-2927 ; 2047-2919
ISSN (online)	2047-2927
ISSN	2047-2919
DOI	10.1111/andr.13566
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Zs.A 6983: Show issues

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Article ; Online: SARS-CoV-2 Nasopharyngeal Swab Testing-False-Negative Results From a Pervasive Anatomical Misconception.

Higgins, Thomas S / Wu, Arthur W / Ting, Jonathan Y

JAMA otolaryngology-- head & neck surgery

2020 Volume 146, Issue 11, Page(s) 993–994

MeSH term(s)	COVID-19/diagnosis ; COVID-19 Nucleic Acid Testing/methods ; COVID-19 Nucleic Acid Testing/standards ; False Negative Reactions ; Humans ; Nasopharynx/anatomy & histology ; Nasopharynx/virology ; SARS-CoV-2
Keywords	covid19
Language	English
Publishing date	2020-09-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	2701825-8
ISSN	2168-619X ; 2168-6181
ISSN (online)	2168-619X
ISSN	2168-6181
DOI	10.1001/jamaoto.2020.2946
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Ul II Zs.87: Show issues

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Article ; Online: Basic Science and Clinical Application of Reamed Sources for Autogenous Bone Graft Harvest.

Higgins, Thomas F / Marchand, Lucas S

The Journal of the American Academy of Orthopaedic Surgeons

2018 Volume 26, Issue 12, Page(s) 420–428

Abstract: Autologous bone graft remains the only clinically available source of graft material with osteogenic, osteoinductive, and osteoconductive properties. Although iliac crest autologous bone graft has long served as the benchmark, reamed autogenous bone ... ...

Abstract	Autologous bone graft remains the only clinically available source of graft material with osteogenic, osteoinductive, and osteoconductive properties. Although iliac crest autologous bone graft has long served as the benchmark, reamed autogenous bone graft offers several advantages. Reamed autograft has a biochemical and cellular profile that is at least equivalent, and perhaps superior, to that of iliac crest autograft. In addition, larger volumes of reamed autograft can be obtained via less-invasive techniques, giving surgeons an accessible source of mesenchymal stem cells that can be reliably and repeatedly harvested. Early clinical experience involving reamed autogenous bone graft in the management of nonunion, bone defects, and arthrodesis has been encouraging and has demonstrated the necessary properties to warrant regular consideration of reamed graft for these applications.
MeSH term(s)	Autografts/cytology ; Autografts/metabolism ; Autografts/physiology ; Bone Morphogenetic Proteins/metabolism ; Bone Transplantation ; Humans ; Osteoblasts ; Osteogenesis ; Stem Cells ; Tissue and Organ Harvesting/adverse effects ; Tissue and Organ Harvesting/instrumentation ; Tissue and Organ Harvesting/methods ; Transplant Donor Site ; Transplantation, Autologous
Chemical Substances	Bone Morphogenetic Proteins
Language	English
Publishing date	2018-05-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	1200524-1
ISSN	1940-5480 ; 1067-151X
ISSN (online)	1940-5480
ISSN	1067-151X
DOI	10.5435/JAAOS-D-16-00512
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Zs.A 4048: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 274: Show issues

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Article: Enhanced bacterial cancer therapy delivering therapeutic RNA interference of c-Myc.

Williams, Jason S / Higgins, Adam T / Stott, Katie J / Thomas, Carly / Farrell, Lydia / Bonnet, Cleo S / Peneva, Severina / Derrick, Anna V / Hay, Trevor / Wang, Tianqi / Morgan, Claire / Dwyer, Sarah / D'Ambrogio, Joshua / Hogan, Catherine / Smalley, Matthew J / Parry, Lee / Dyson, Paul

Cell & bioscience

2024 Volume 14, Issue 1, Page(s) 38

Abstract: Background: Bacterial cancer therapy was first trialled in patients at the end of the nineteenth century. More recently, tumour-targeting bacteria have been harnessed to deliver plasmid-expressed therapeutic interfering RNA to a range of solid tumours. ... ...

Abstract	Background: Bacterial cancer therapy was first trialled in patients at the end of the nineteenth century. More recently, tumour-targeting bacteria have been harnessed to deliver plasmid-expressed therapeutic interfering RNA to a range of solid tumours. A major limitation to clinical translation of this is the short-term nature of RNA interference in vivo due to plasmid instability. To overcome this, we sought to develop tumour-targeting attenuated bacteria that stably express shRNA by virtue of integration of an expression cassette within the bacterial chromosome and demonstrate therapeutic efficacy in vitro and in vivo. Results: The attenuated tumour targeting Salmonella typhimurium SL7207 strain was modified to carry chromosomally integrated shRNA expression cassettes at the xylA locus. The colorectal cancer cell lines SW480, HCT116 and breast cancer cell line MCF7 were used to demonstrate the ability of these modified strains to perform intracellular infection and deliver effective RNA and protein knockdown of the target gene c-Myc. In vivo therapeutic efficacy was demonstrated using the Lgr5creER Conclusions: In summary we have demonstrated that tumour tropic bacteria can be modified to safely deliver therapeutic levels of gene knockdown. This technology has the potential to specifically target primary and secondary solid tumours with personalised therapeutic payloads, providing new multi-cancer detection and treatment options with minimal off-target effects. Further understanding of the tropism mechanisms and impact on host immunity and microbiome is required to progress to clinical translation.
Language	English
Publishing date	2024-03-23
Publishing country	England
Document type	Journal Article
ZDB-ID	2593367-X
ISSN	2045-3701
ISSN	2045-3701
DOI	10.1186/s13578-024-01206-8
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Article ; Online: Multi-Institutional Analysis of Insurance Denial Patterns Within Rhinology.

Janz, Tyler A / Khan, Najm S / Dhanda, Aatin K / Takashima, Masayoshi / Wu, Arthur W / Tang, Dennis M / Higgins, Thomas S / Ramanathan, Murugappan / Ahmed, Omar G

American journal of rhinology & allergy

2024 , Page(s) 19458924241242856

Abstract: Background: Obtaining insurance approval is a necessary component of healthcare in the United States and denials of these claims have been estimated to result in a loss of 3% to 5% of revenue.: Objective: Examine the trends in insurance denials for ... ...

Abstract	Background: Obtaining insurance approval is a necessary component of healthcare in the United States and denials of these claims have been estimated to result in a loss of 3% to 5% of revenue. Objective: Examine the trends in insurance denials for rhinological procedures. Methods: A retrospective review of deidentified financial data of patients who were treated by participating physicians across 3 institutions from January 1, 2021, to June 30, 2023. The data was queried for rhinological and non-rhinological procedures via CPT codes. Cumulative insurance denials were calculated and stratified by procedure and insurance type. Write-offs were dollar amounts associated with final denials. Results: A sample of 102,984 procedures and visits revealed a final denial rate between 2.2% and 2.9% across institutions ( Conclusion: Final denial rates of rhinology procedures ranged between 2% and 3%. Common procedures such as nasal endoscopy and nasal debridement are among the highest written-off procedures. Insurance denials can lead to notable revenue loss. Rhinology practices must continue to remain knowledgeable of the changes and effects of insurance reimbursement on their practice.
Language	English
Publishing date	2024-03-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	2482804-X
ISSN	1945-8932 ; 1945-8924
ISSN (online)	1945-8932
ISSN	1945-8924
DOI	10.1177/19458924241242856
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Zs.A 2542: Show issues

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Article ; Online: Butterfly fragments in diaphyseal tibial fractures heal unpredictably: Should we be adopting other strategies for these high risk fractures?

Myhre, Luke / Steffenson, Lillia / Higgins, Thomas F / Rothberg, David L / Haller, Justin M / Marchand, Lucas S

Injury

2022 Volume 54, Issue 2, Page(s) 738–743

Abstract: Introduction: The natural history of diaphyseal tibial butterfly fragments is poorly documented. Numerous studies have analyzed risk factors for nonunions in the tibial shaft with known factors including Gustilo classification, ASA class, and cortical ... ...

Abstract	Introduction: The natural history of diaphyseal tibial butterfly fragments is poorly documented. Numerous studies have analyzed risk factors for nonunions in the tibial shaft with known factors including Gustilo classification, ASA class, and cortical contact. However, the healing potential and ideal management of nonsegmental butterfly fragments in this setting remains unknown. The aim of this study was to determine the nonunion rate of diaphyseal tibial fractures with a butterfly fragment. Methods: A performed a retrospective review of patients at a single academic Level 1 Trauma Center from 2000-2020 who underwent intramedullary nailing of tibial shaft fractures. Those with non-segmental butterfly fragments (OTA/AO: 42-B) and minimum 12 month follow up were included. Morphologic measurements of butterfly fragments were performed to measure location, size, and displacement, and mRust scores at final follow up were calculated. Outcome measures were surgery to promote union, and mRust scores. Results: A total of 99 patients were included with 21 patients requiring revision surgery to promote union. Thirty six patients had open fractures and 77% of patients were male with a mean age of 34 (range: 12-80). Average follow up was 19 months (3 months - 12 years). The most common location of the butterfly fragment was the anterior cortex (42%), with a mean length of 7.8cm (SD: 3.3) and width of 1.8cm (SD: 0.5cm). At final follow-up 37% of fractures had persistent lucency without callus at the site of the butterfly while only 31% of fractures had remodeled cortex. Average time to complete healing was 13.3 months. Open fractures with butterfly fragments were more likely to go on to nonunion than closed (44% vs 9.2%, p=<0.001). The length of the butterfly fragment was not different between the union and nonunion groups (7.7 vs 7.5, P=0.42). Conclusions: Open tibial shaft fractures with a butterfly fragment have a high risk of nonunion. Further research may seek to determine if adjunct treatment of butterfly fragments (ie inter-fragmentary compression) in the acute setting could improve healing rates.
MeSH term(s)	Humans ; Male ; Animals ; Adult ; Female ; Butterflies ; Fractures, Open/diagnostic imaging ; Fractures, Open/surgery ; Fractures, Open/etiology ; Fracture Healing ; Treatment Outcome ; Tibial Fractures/diagnostic imaging ; Tibial Fractures/surgery ; Fracture Fixation, Intramedullary/adverse effects ; Retrospective Studies ; Bone Nails
Language	English
Publishing date	2022-12-24
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	218778-4
ISSN	1879-0267 ; 0020-1383
ISSN (online)	1879-0267
ISSN	0020-1383
DOI	10.1016/j.injury.2022.12.024
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Zs.A 778: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 10: Show issues

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