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Article ; Online: Immunologic landscape of human hepatic hemangiomas and epithelioid hemangioendotheliomas.

Thomann, Stefan / Metzler, Thomas / Tóth, Marcell / Schirmacher, Peter / Mogler, Carolin

Hepatology communications

2024 Volume 8, Issue 1

Abstract: Background: The missing requirement for resection for the majority of hepatic hemangiomas (HH) and tissue scarcity for rare diseases such as hepatic epithelioid hemangioendotheliomas (HEHE) complicate the characterization of the spatial immunovascular ... ...

Abstract	Background: The missing requirement for resection for the majority of hepatic hemangiomas (HH) and tissue scarcity for rare diseases such as hepatic epithelioid hemangioendotheliomas (HEHE) complicate the characterization of the spatial immunovascular niche of these benign and malignant vascular neoplastic diseases. Methods: Two tissue cohorts containing 98 HHs and 13 HEHEs were used to study entity-specific and disease stage-specific endothelial cell (EC) phenotype and immune cell abundance. Using semiquantitative assessment, annotation-based cell classifiers, digital cell detection on whole slides, and tissue microarrays, we quantified 23 immunologic and vascular niche-associated markers and correlated this with clinicopathologic data. Results: Both HH and HEHE ECs were characterized by a CD31high, CD34high, FVIII-related antigenhigh expression phenotype with entity-specific expression differences of sinusoidal EC markers Stabilin1, Stabilin2, CD32, and Lymphatic Vessel Endothelial Hyaluronan Receptor 1 (LYVE-1). Cell detection identified an HH margin-prevailing immunologic response dominated by Myeloperoxidase+ (MPO+) macrophages, CD3+ and CD8+ T cell subsets, and B cells (CD20+, CD79A+). In HEHE, increased CD68+ and CD20+ cell demarcation of lesion margins was observed, while CD3+ and CD8+ T cells were equally detectable both marginally and intralesionally. Stage-specific pairwise correlation analysis of HH and HEHE revealed disease entity-specific immunologic infiltration patterns as seen by high CD117+ cell numbers in HH, while HEHE samples showed increased CD3+ T cell infiltration. Conclusions: ECs in HH and HEHE share a continuous EC expression phenotype, while the expression of sinusoidal EC markers is more highly retained in HEHE. These phenotypic differences are associated with a unique and disease-specific immunovascular landscape.
MeSH term(s)	Humans ; Hemangioendothelioma, Epithelioid ; Hemangioma ; Liver Neoplasms ; Endothelial Cells ; CD8-Positive T-Lymphocytes
Language	English
Publishing date	2024-01-11
Publishing country	United States
Document type	Journal Article
ISSN	2471-254X
ISSN (online)	2471-254X
DOI	10.1097/HC9.0000000000000359
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Book ; Thesis: Präoperative Digitalisierung in der Anästhesie

Metzler, Thomas K.

1989

Author's details	vorgelegt von Thomas Karlheinz Metzler
Size	87 S. : graph. Darst.
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Lübeck, Med. Univ., Diss., 1990
HBZ-ID	HT003780664
Database	Catalogue ZB MED Medicine, Health

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Article ; Online: Brief behavioral treatment for insomnia decreases trauma-related nightmare frequency in veterans.

Ranney, Rachel M / Gloria, Rebecca / Metzler, Thomas J / Huggins, Joy / Neylan, Thomas C / Maguen, Shira

Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine

2022 Volume 18, Issue 7, Page(s) 1831–1839

Abstract: Study objectives: Trauma-related nightmares are highly prevalent among veterans and are associated with higher-severity insomnia and posttraumatic stress disorder. Cognitive behavioral therapy for insomnia (typically 6-8 sessions) has been shown to ... ...

Abstract	Study objectives: Trauma-related nightmares are highly prevalent among veterans and are associated with higher-severity insomnia and posttraumatic stress disorder. Cognitive behavioral therapy for insomnia (typically 6-8 sessions) has been shown to reduce trauma-related nightmares. Brief behavioral treatment for insomnia (BBTI, 4 sessions) has been found to be comparable to CBT-I in decreasing insomnia severity; however, the effects of BBTI on nightmares have not been investigated. The current study tested the effects of BBTI on both trauma-related nightmares and nontrauma-related bad dreams using an active control group treated using progressive muscle relaxation therapy. In addition, we tested whether baseline trauma-related nightmare frequency and baseline nontrauma-related bad dream frequency moderated changes in insomnia severity. Methods: Participants were 91 military veterans with insomnia disorder randomized to BBTI or progressive muscle relaxation therapy. Participants reported insomnia severity on the Insomnia Severity Index and reported trauma-related nightmare frequency and nontrauma-related bad dream frequency on the Pittsburgh Sleep Quality Index-PTSD Addendum. Results: We found that BBTI significantly reduced trauma-related nightmares from baseline to posttreatment, whereas progressive muscle relaxation therapy did not. However, reductions in trauma-related nightmares were not maintained at the 6-month follow up. Neither BBTI nor progressive muscle relaxation therapy reduced nontrauma-related bad dreams from baseline to posttreatment. We also found that neither baseline trauma-related nightmare frequency nor baseline nontrauma-related bad dream frequency moderated changes in insomnia symptom severity. Conclusions: Findings from the current study suggest that BBTI may help reduce trauma-related nightmares. Further research is needed to better understand the potential mechanisms underlying how improved sleep may reduce trauma-related nightmares. Clinical trial registration: Registry: ClinicalTrials.gov; Name: Brief Behavioral Insomnia Treatment Study (BBTI); URL: https://clinicaltrials.gov/ct2/show/NCT02571452; Identifier: NCT02571452. Citation: Ranney RM, Gloria R, Metzler TJ, Huggins J, Neylan TC, Maguen S. Brief behavioral treatment for insomnia decreases trauma-related nightmare frequency in veterans.
MeSH term(s)	Cognitive Behavioral Therapy ; Dreams/psychology ; Humans ; Sleep Initiation and Maintenance Disorders/complications ; Sleep Initiation and Maintenance Disorders/therapy ; Stress Disorders, Post-Traumatic/complications ; Stress Disorders, Post-Traumatic/diagnosis ; Stress Disorders, Post-Traumatic/therapy ; Treatment Outcome ; Veterans/psychology
Language	English
Publishing date	2022-04-06
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2397213-0
ISSN	1550-9397 ; 1550-9389
ISSN (online)	1550-9397
ISSN	1550-9389
DOI	10.5664/jcsm.10002
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Article ; Online: Molecular Genetic Investigation of Digital Melanoma in Dogs.

Conrad, David / Kehl, Alexandra / Beitzinger, Christoph / Metzler, Thomas / Steiger, Katja / Pfarr, Nicole / Fischer, Konrad / Klopfleisch, Robert / Aupperle-Lellbach, Heike

Veterinary sciences

2022 Volume 9, Issue 2

Abstract: Canine digital melanoma, in contrast to canine oral melanoma, is still largely unexplored at the molecular genetic level. The aim of this study was to detect mutant genes in digital melanoma. Paraffin-embedded samples from 86 canine digital melanomas ... ...

Abstract	Canine digital melanoma, in contrast to canine oral melanoma, is still largely unexplored at the molecular genetic level. The aim of this study was to detect mutant genes in digital melanoma. Paraffin-embedded samples from 86 canine digital melanomas were examined for the
Language	English
Publishing date	2022-01-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2768971-2
ISSN	2306-7381 ; 2306-7381
ISSN (online)	2306-7381
ISSN	2306-7381
DOI	10.3390/vetsci9020056
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Article ; Online: Pretreatment stabilization increases completion of trauma-focused evidence-based psychotherapies.

Staudenmeyer, Anna H / Maxwell, Susan / Mohlenhoff, Brian / Yasser, Julia / Schmitz, Martha / Metzler, Thomas / Maguen, Shira / Neylan, Thomas / Wolfe, William

Psychological trauma : theory, research, practice and policy

2022

Abstract: Objective: Veterans with posttraumatic stress disorder (PTSD) initiate and complete cognitive processing therapy (CPT) and prolonged exposure (PE) at low rates within Veterans Health Administration (VHA) despite substantial dissemination and training. ... ...

Abstract	Objective: Veterans with posttraumatic stress disorder (PTSD) initiate and complete cognitive processing therapy (CPT) and prolonged exposure (PE) at low rates within Veterans Health Administration (VHA) despite substantial dissemination and training. This study investigated how trauma-informed, skills-based treatment ("stabilization") administered before CPT and PE was related to initiation and completion of trauma-focused evidence-based psychotherapies (TF-EBPs). Method: Data were extracted from the VHA electronic medical record to identify veterans who initiated outpatient treatment in the PTSD Clinical Team (PCT) at a Veterans Affairs Health Care System. Treatment initiation was defined as three or more PCT visits with no prior PCT care for at least 18 months ( Results: Twenty-eight percent of veterans without stabilization ( Conclusions: Findings suggest that individual stabilization may improve delivery of TF-EBPs in VHA settings by increasing TF-EBP completion without reducing initiation, while pretreatment with group-only stabilization may reduce initiation of TF-EBPs. Results inform how models of care can improve TF-EBP retention and completion among veterans with PTSD. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
Language	English
Publishing date	2022-05-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	2497028-1
ISSN	1942-969X ; 1942-9681
ISSN (online)	1942-969X
ISSN	1942-9681
DOI	10.1037/tra0001196
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Article ; Online: The sleep physiology of nightmares in veterans with psychological trauma: Evaluation of a dominant model using participant-applied electroencephalography in the home environment.

Richards, Anne / Woodward, Steven H / Baquirin, David Paul G / Yack, Leslie M / Metzler, Thomas J / Udupa, Nikhila S / Staggs, Emily J / Neylan, Thomas C

Journal of sleep research

2022 Volume 32, Issue 2, Page(s) e13639

Abstract: Nightmares are a core feature of posttraumatic stress disorder, are poorly understood, and are associated with serious negative outcomes. Their biology has been difficult to study, and the feasibility of capturing them in the naturalistic home ... ...

Abstract	Nightmares are a core feature of posttraumatic stress disorder, are poorly understood, and are associated with serious negative outcomes. Their biology has been difficult to study, and the feasibility of capturing them in the naturalistic home environment has been poor. This said, the published research and dominant scientific model has focused on nightmares as a manifestation of noradrenergic hyperarousal during rapid eye movement sleep. The current study used at-home, participant-applied devices to measure nightmare physiology in posttraumatic stress disorder treatment-seeking veterans, by examining heartrate measures as indicators of noradrenergic tone, and sleep-stage characteristics and stability in the sleep preceding time-stamped nightmare awakenings. Our data indicate the high feasibility of participant-administered, at-home measurement, and showed an unexpected stability of -rapid eye movement sleep along with no evidence of heartrate elevations in sleep preceding nightmare awakenings. Altogether, these data highlight new opportunities for the study of nightmares while questioning the sufficiency of dominant models, which to date are largely theoretically based.
MeSH term(s)	Humans ; Dreams/psychology ; Veterans/psychology ; Home Environment ; Sleep ; Psychological Trauma/complications ; Stress Disorders, Post-Traumatic/psychology ; Electroencephalography ; Sleep Wake Disorders/complications
Language	English
Publishing date	2022-05-29
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
ZDB-ID	1122722-9
ISSN	1365-2869 ; 0962-1105
ISSN (online)	1365-2869
ISSN	0962-1105
DOI	10.1111/jsr.13639
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Zs.A 3464: 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)
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Article: Molecular Genetic Investigation of Digital Melanoma in Dogs

Conrad, David / Kehl, Alexandra / Beitzinger, Christoph / Metzler, Thomas / Steiger, Katja / Pfarr, Nicole / Fischer, Konrad / Klopfleisch, Robert / Aupperle-Lellbach, Heike

Veterinary sciences. 2022 Jan. 30, v. 9, no. 2

2022

Abstract	Canine digital melanoma, in contrast to canine oral melanoma, is still largely unexplored at the molecular genetic level. The aim of this study was to detect mutant genes in digital melanoma. Paraffin-embedded samples from 86 canine digital melanomas were examined for the BRAF V595E variant by digital droplet PCR (ddPCR), and for exon 11 mutations in c-kit. Furthermore, exons 2 and 3 of KRAS and NRAS were analysed by Sanger sequencing. Copy number variations (CNV) of KITLG in genomic DNA were analysed from nine dogs. The BRAF V595E variant was absent and in c-kit, a single nucleotide polymorphism was found in 16/70 tumours (23%). The number of copies of KITLG varied between 4 and 6. KRAS exon 2 codons 12 and 13 were mutated in 22/86 (25.6%) of the melanomas examined. Other mutually exclusive RAS mutations were found within the hotspot loci, i.e., KRAS exon 3 codon 61: 2/55 (3.6%); NRAS exon 2 codons 12 and 13: 2/83 (2.4%); and NRAS exon 3 codon 61: 9/86 (10.5%). However, no correlation could be established between histological malignancy criteria, survival times and the presence of RAS mutations. In summary, canine digital melanoma differs from molecular genetic data of canine oral melanoma and human melanoma, especially regarding the proportion of RAS mutations.
Keywords	DNA ; codons ; dogs ; droplets ; exons ; histology ; humans ; melanoma ; mutants ; single nucleotide polymorphism
Language	English
Dates of publication	2022-0130
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2768971-2
ISSN	2306-7381
ISSN	2306-7381
DOI	10.3390/vetsci9020056
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Longitudinal association of PTSD symptoms and self-reported physical functioning among Veterans.

Ahmadian, Ashkan J / Neylan, Thomas C / Metzler, Thomas / Cohen, Beth E

Journal of affective disorders

2019 Volume 250, Page(s) 1–8

Abstract: Background: Few longitudinal studies have investigated the potentially dynamic relationship between Posttraumatic Stress Disorder (PTSD) and physical functioning, and the number of follow-up timepoints have been limited. We evaluated whether PTSD ... ...

Abstract	Background: Few longitudinal studies have investigated the potentially dynamic relationship between Posttraumatic Stress Disorder (PTSD) and physical functioning, and the number of follow-up timepoints have been limited. We evaluated whether PTSD symptoms predicted future physical functioning and vice versa using five assessments over four years. Methods: Data was used from a longitudinal cohort of 695 participants recruited from Veteran Affairs medical outpatient clinics who experienced a traumatic event. PTSD symptom severity was assessed annually with the PTSD Checklist (PCL). Physical functioning was measured with the 10-item subscale of the SF-36. An autoregressive cross-lagged panel model was used to determine the temporal associations between PTSD and physical functioning, adjusting for age, sex, ethnicity, education and employment. Comorbidities and health behaviors were added to assess their roles in the relationship. Results: Greater PTSD symptom severity predicted worse physical functioning the following year (average β = -0.10, P <0.001), where a 10-point increase in PCL score predicted a 0.3-point decline in physical function score over one year. Similarly, better physical functioning also predicted reduced PTSD severity the following year, but to a smaller magnitude (average β = -0.04, P = .003). The pattern of effects was similar after controlling for comorbidities and health behaviors. Limitations: Both primary variables relied on self-report, and generalizability may be limited by the mostly male Veteran sample. Conclusions: Our results support a bidirectional, but unequal, relationship between PTSD and physical functioning over time. They also highlight the importance of long-term control of PTSD symptoms in preventing functional decline.
MeSH term(s)	Activities of Daily Living ; Aged ; Checklist ; Disability Evaluation ; Female ; Health Behavior ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Quality of Life ; Self Report ; Socioeconomic Factors ; Stress Disorders, Post-Traumatic/complications ; Stress Disorders, Post-Traumatic/psychology ; Veterans/psychology ; War-Related Injuries/complications
Language	English
Publishing date	2019-02-19
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	135449-8
ISSN	1573-2517 ; 0165-0327
ISSN (online)	1573-2517
ISSN	0165-0327
DOI	10.1016/j.jad.2019.02.048
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Zs.A 1485: Show issues

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Article ; Online: Simultaneous magnetic resonance imaging of pH, perfusion and renal filtration using hyperpolarized

Grashei, Martin / Wodtke, Pascal / Skinner, Jason G / Sühnel, Sandra / Setzer, Nadine / Metzler, Thomas / Gulde, Sebastian / Park, Mihyun / Witt, Daniela / Mohr, Hermine / Hundshammer, Christian / Strittmatter, Nicole / Pellegata, Natalia S / Steiger, Katja / Schilling, Franz

Nature communications

2023 Volume 14, Issue 1, Page(s) 5060

Abstract: pH alterations are a hallmark of many pathologies including cancer and kidney disease. Here, we introduce [1,5- ...

Abstract	pH alterations are a hallmark of many pathologies including cancer and kidney disease. Here, we introduce [1,5-
MeSH term(s)	Animals ; Rats ; Perfusion ; Magnetic Resonance Imaging ; Filtration ; Glomerular Filtration Rate ; Hydrogen-Ion Concentration
Language	English
Publishing date	2023-08-21
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-40747-3
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Article ; Online: Sleep Spindles Favor Emotion Regulation Over Memory Consolidation of Stressors in Posttraumatic Stress Disorder.

Natraj, Nikhilesh / Neylan, Thomas C / Yack, Leslie M / Metzler, Thomas J / Woodward, Steven H / Hubachek, Samantha Q / Dukes, Cassandra / Udupa, Nikhila S / Mathalon, Daniel H / Richards, Anne

Biological psychiatry. Cognitive neuroscience and neuroimaging

2023 Volume 8, Issue 9, Page(s) 899–908

Abstract: Background: Posttraumatic stress disorder (PTSD) is a trauma-induced condition, characterized by intrusive memories and trauma-associated anxiety. Non-rapid eye movement (NREM) sleep spindles might play a crucial role in learning and consolidating ... ...

Abstract	Background: Posttraumatic stress disorder (PTSD) is a trauma-induced condition, characterized by intrusive memories and trauma-associated anxiety. Non-rapid eye movement (NREM) sleep spindles might play a crucial role in learning and consolidating declarative stressor information. However, sleep and possibly sleep spindles are also known to regulate anxiety, suggestive of a dual role for sleep spindles in the processing of stressors. Specifically, in individuals with high PTSD symptom burden, spindles might fail to regulate anxiety levels after exposure and instead might maladaptively consolidate stressor information. Methods: To disentangle the role of spindles in declarative memory versus anxiety regulation after stressor exposure and to examine the role of PTSD in these processes, we measured nap sleep after a cohort of 45 trauma-exposed participants were exposed to laboratory stress. Participants (high vs. low PTSD symptoms) completed 2 visits: a stress visit involving exposure to negatively valent images before nap and a control visit. In both visits, sleep was monitored via electroencephalography. A stressor recall session occurred after the nap in the stress visit. Results: Stage 2 NREM (NREM2) spindle rates were higher in stress versus control sleep, indicative of stress-induced changes in spindles. In participants with high PTSD symptoms, NREM2 spindle rates in stress sleep predicted poorer recall accuracy of stressor images relative to participants with low PTSD symptoms, while correlating with greater reduction in stressor-induced anxiety levels after sleep. Conclusions: Contrary to our expectations, although spindles are known to play a role in declarative memory processes, our findings highlight an important role for spindles in sleep-dependent anxiety regulation in PTSD.
MeSH term(s)	Humans ; Memory Consolidation/physiology ; Stress Disorders, Post-Traumatic ; Emotional Regulation ; Sleep/physiology ; Memory/physiology
Language	English
Publishing date	2023-03-06
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2879089-3
ISSN	2451-9030 ; 2451-9022
ISSN (online)	2451-9030
ISSN	2451-9022
DOI	10.1016/j.bpsc.2023.02.007
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