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Einfluss der rekanalisierenden Schlaganfalltherapie auf die Inzidenz von frühen Post-Stroke-Krampfanfällen
Get PDF1.1 Deutsche Zusammenfassung
1.1.1 Einleitung
Die rekanalisierende Schlaganfalltherapie in Form von intravenöser Thrombolyse und endovaskulärer
Schlaganfalltherapie stellt den bedeutendsten kurativen Interventionsansatz in der Behandlung des is
chämischen Schlaganfalls dar. Insbesondere die systemische Thrombolyse mit Alteplase (rt-PA) konnte
in den letzten Jahren wiederholt mit neurotoxischem und epileptogenen Potential in Verbindung ge
bracht werden. Ihre Rolle in der Entwicklung von Post-Stroke-Krampfanfällen (PSS) und -Epilepsie
(PSE) in-vivo bleibt jedoch umstritten. Ziel der Arbeit stellt die weiterführende Untersuchung der reka
nalisierenden Therapien und anderer patienten- und schlaganfallbezogener Einflussgrößen als Risiko
faktor für die Entstehung von frühen Post-Stroke-Krampfanfällen innerhalb der ersten 7 Tage nach is
chämischem Schlaganfall dar. Weiterhin soll eine nähere klinische Charakterisierung des betroffenen
Patientenkollektivs durchgeführt werden.
1.1.2 Material und Methode
Wir führten ein systematisches Review bezüglich des Zusammenhangs zwischen der rekanalisierenden
Schlaganfalltherapie und dem Auftreten von Post-Stroke-Krampfanfällen, sowie deren Einfluss auf
Morbidität und Mortalität, durch. Die Database Medline (über Pubmed) wurde von Beginn bis April
2017 durchsucht. 13 Studien konnten insgesamt in das Review aufgenommen werden. Weiterhin führten
wir eine retrospektiv konzipierte Fall-Kontroll-Studie durch. Hierfür identifizierten wir retrospektiv alle
Patienten, welche zwischen 2010 und 2016 an der Stroke-Unit des Universitätsklinikums des Saarlandes
einen Krampfanfall innerhalb von 7 Tagen nach akutem Schlaganfall erlitten haben und matchten diese
nach Alter und Geschlecht. 79 Fälle und 158 Kontrollen konnten in die Studie eingeschlossen und hin
sichtlich Therapieinterventionen, schlaganfall-, sowie patientenbezogenen Parametern, Gruppenverglei
chen, einer univariaten logistischen Regressionsanalyse, sowie einer multivariaten Analyse mit Vor
wärts- und Rückwärtsselektion unterzogen werden. Eine Stichprobe von 32 Patienten, welche frühe
Post-Stroke-Krampfanfälle nach rekanalisierender Therapieintervention entwickelten, wurden zusätz
lich deskriptiv klinisch charakterisiert. Patienten mit transitorischer ischämischer Attacke (TIA), vorbe
kannter Epilepsie, primärem hämorrhagischem Ereignis, sowie intrakranieller Raumforderung oder in
flammatorischem Geschehen wurden ausgeschlossen.
1
1.1.3 Ergebnis
Die Studien, welche in das systematische Review aufgenommen werden konnten, zeigten starke Inho
mogenitäten hinsichtlich Studiendesign, Follow-Up, Begriffsdefinitionen und Ergebnis. Nur eine retro
spektive Studie konnte einen signifikanten Zusammenhang zwischen systemischer Thrombolyse und
Post-Stroke-Krampfanfall ermitteln. Keine Studie untersuchte spezifisch den Einfluss der endovaskulä
ren Schlaganfalltherapie. Als gut untersuchte Risikofaktoren zeigten sich die kortikale Beteiligung (5),
der Schweregrad des Schlaganfalls (5) und die hämorrhagische Transformation (2). Alle Studien, wel
che den entsprechenden Zusammenhang untersuchten, konnten einen signifikanten Zusammenhang
zwischen Post-Stroke-Krampfanfällen und schlechterem funktionalen Outcome beobachten. 3 von 4
Studien fanden eine signifikante Assoziation zu einer erhöhten Mortalität. Es konnten 32 Patienten mit
frühem Post-Stroke-Krampfanfall nach Thrombolyse und/oder endovaskulärer Schlaganfallbehandlung
identifiziert werden (mittleres Alter 75 Jahre, 56,3% männlich). 25 erhielten eine intravenöse Throm
bolyse, 7 eine intraarterielle Thrombolyse und 16 eine mechanische Thrombektomie. Die meisten Pati
enten hatten keine Vorgeschichte eines Schlaganfalls (56,3%), einer Alkoholabhängigkeit (93,8%), ei
nes Diabetes (59,4%) und nahmen nicht regelmäßig Statine (59,4%), oder Antikoagulantien (90,6%)
ein. Die Hälfte nahm Thrombozytenaggregationshemmer. 71,9% der Schlaganfälle wies eine kortikale
Beteiligung auf. Der mediane NIHSS-Score bei Aufnahme betrug 12, der mediane Punktewert auf der
modifizierten Rankin-Skala 4. Als häufigste Anfallsform zeigten sich einfach fokale Anfälle ohne se
kundäre Generalisierung (43,8%), gefolgt von generalisiert tonisch-klonischen Anfällen (40,6%). 50%
der Krampfanfälle wurden bereits am ersten Tag nach zerebrovaskulärem Ereignis beobachtet. In der
Fall-Kontroll-Studie zeigten sich die systemische Thrombolyse mit Alteplase (rt-PA), die Infarktlokali
sation, der Schlaganfallschweregrad auf NIHSS- und Rankin-Skala, sowie der Blutzuckerwert bei Auf
nahme in der univariaten Analyse signifikant mit dem Auftreten von frühen Post-Stroke-Krampfanfällen
assoziiert. Nach multivariater Analyse mit Vorwärts- und Rückwärtsselektion verblieben noch die in
travenöse Thrombolyse mit rt-PA (OR 2.26; 95% CI 1.16-4.43) und die kortikale Schlaganfalllokalisa
tion (OR 2.49; 95% CI 1.35- 4.59; p = 0.003) als signifikante, unabhängige Risikofaktoren im Modell.
1.1.4 Schlussfolgerung
Frühe Post-Stroke Krampfanfälle sind typischerweise einfach fokal oder generalisiert tonisch-klonisch,
treten meist bereits in den ersten 24-72 Stunden nach Schlaganfall auf und haben einen negativen Ein
fluss auf Morbidität und Mortalität. Kortikale Beteiligung und intravenöse Thrombolyse sind unabhän
gige Risikofaktoren für ihre Entwicklung. Ihr Einfluss kann nicht durch Alter, Geschlecht, Schlagan
fallschweregrad, -Ätiologie, hämorrhagischer Transformation, Vorerkrankungen, Laborparameter bei
Aufnahme oder die vorbestehende Sekundärprophylaxe erklärt werden. Diese Ergebnisse sind konkor
dant mit denen bisheriger retrospektiver Studien mit kleinerer Fallzahl und anderem Studienaufbau, ste
hen jedoch in Diskrepanz zu einigen prospektiven Studien und Meta-Analysen. Reperfusion durch
2
endovaskuläre Schlaganfalltherapie zeigte sich nicht signifikant mit dem Auftreten von frühen Post
Stroke-Krampfanfällen assoziiert. Es bedarf weiterführender randomisierter, prospektiver Studien mit
neurophysiologischem Monitoring um die Frage nach dem Einfluss der rekanalisierenden Schlaganfall
therapie in der Entstehung von Post-Stroke-Krampfanfällen abschließend bewerten zu können.1.2 Abstract
1.2.1 Background
Over the last few years, there has been a growing body of evidence that thrombolysis with rt-PA and
mechanic thrombectomy might have neurotoxic and epileptogenic potential. Nevertheless, the role of
reperfusion therapies in the development of post-stroke seizure (PSS) and post-stroke epilepsy (PSE) is
still uncertain. The aim of our study was to investigate reperfusion therapies, stroke characteristics, and
patients' characteristics on admission as risk factors for early post-stroke seizures in the first 7 days after
acute ischemic stroke.
1.2.2 Methods
First, we performed a systematic review to evaluate the association between intravenous thrombolysis
and the occurrence of post-stroke seizures, find other risk factors for post-stroke seizures (PSS), and
determine the impact they have on clinical outcome and mortality. We searched the database MEDLINE
(through Pubmed) from inception to April 18, 2017. A total of thirteen studies were included in the
review. Furthermore, we undertook a retrospective case-control study at a single stroke center. We iden
tified all patients with seizures occurring the first 7 days after acute ischemic stroke and matched them
for age and gender. We included 79 cases and 158 controls and undertook a multivariate logistic regres
sion regarding therapy, stroke characteristics, and patient characteristics on admission. Additionally, we
performed descriptive statistics for 32 patients who suffered acute seizures following thrombolysis
and/or mechanical thrombectomy. Patients with TIA, known epilepsy, primary hemorrhagic insult, in
tracranial tumor, or inflammation were excluded from the study.
1.2.3 Results
The studies included in the systematic review differed strongly regarding results, definitions, follow-up
and study design. Only one retrospective study found a significant association between intravenous
thrombolysis and the occurrence of PSS - no study investigated specifically the influence of mechanical
thrombectomy. Variables most frequently associated with PSS were cortical involvement (5), stroke
severity (5), and hemorrhagic transformation (2). All studies regarding the issue found a significant
association between post-stroke seizures and poor functional outcomes. 3 out of 4 studies showed a
3
significant association between post-stroke seizures and increased mortality. We identified and explored
the characteristics of 32 patients with seizures following treatment with thrombolysis and/or throm
bectomy after acute ischemic stroke (mean age 75 years, 56% male). 25 patients were treated with in
travenous and 7 with intraarterial thrombolysis, whereas 16 underwent mechanical thrombectomy. Most
patients did not have a prior history of stroke (56.3%), alcoholism (93.8%) or diabetes (59.4%), did not
take statins (59.4%), anticoagulants (90.6%) or had a diagnosis of hypertension (93.8%). Half of them
(50%) was treated with antiplatelet agents. 71.9% of the strokes showed a cortical involvement. Median
NIHSS- and modified Rankin Scale on admission were 12 and 4. A hemorrhagic transformation oc
curred in 21.9% of the cases. The most frequent subtype was focal-onset aware seizure (not secondarily
generalized) (43,8%), followed by primarily generalized seizure (40,6%). 50% of the seizures occurred
within the first 24 hours after cerebrovascular incident. In univariate analysis, blood sugar levels on
admission, stroke localisation, NIHSS-, modified Rankin Scale, and intravenous thrombolysis with rt
PA were statistically associated with early PSS. Multivariate logistic regression after forward and back
ward variable selection identified cortical involvement (OR 2.49; 95% CI 1.35 to 4.59; p= 0.003) and
intravenous thrombolysis (OR 2.26; 95% CI 1.16 to 4.43) as being independently associated with the
occurrence of early PSS.
1.2.4 Conclusions
Early PSS are typically focal-onset aware or primarily generalized seizures, occur within 24 to 72 hours
after cerebrovascular incident, and have a significant impact on poor functional outcome and increased
mortality. Cortical involvement and intravenous thrombolysis are independent risk factors for their de
velopment. This association is not explained by age or gender, concomitant drugs, diabetes, alcoholism,
sodium and cholesterol levels, blood pressure on admission, stroke etiology, stroke severity, hemor
rhagic transformation, or hemorrhage following i.v. thrombolysis. Reperfusion due to mechanical
thrombectomy is not significantly associated with the occurrence of early PSS. Our results are consistent
with those of previous retrospective studies with different study methods, conducted in smaller popula
tions, but differ from those of prospective studies and one meta-analysis. Further studies with a prospec
tive and randomized-controlled design are required to fully evaluate the association between reperfusion
therapies and early PSS
eCPR bei postpartaler Lungenembolie
Get PDFEine 36-jährige Patientin (Gravida VI, Para V) stellte sich zur elektiven Sectio caesarea in der 37 + 1 Schwangerschaftswoche vor. Anamnestisch bestanden ein insulinpflichtiger Gestationsdiabetes sowie eine familiäre Thrombophilie. Eigenanamnestisch war bislang keine Thrombose aufgetreten. Aufgrund des Body-Mass-Index von 42 kg/m2, des Gestationsdiabetes und der positiven Familienanamnese für Thrombophilie wurde die Schwangerschaft als Risikoschwangerschaft eingestuft. Der Kaiserschnitt erfolgte in Spinalanästhesie und verlief komplikationslos.
Am Folgetag der Sectio gab die Patientin im Rahmen der Mobilisation auf der Entbindungsstation plötzliche massive Dyspnoe an und synkopierte. Die Patientin wurde auf die gynäkologische Überwachungsstation verlegt. Sie war tachykard (bis 160 bpm), hypoton (50/30 mm Hg), kaltschweißig und hypoxisch.
Kurz darauf verlor die Patientin das Bewusstsein, und es war kein Puls mehr tastbar – unverzüglich wurden Reanimationsmaßnahmen begonnen. Bei Eintreffen des klinikinternen Notfallteams wurde eine mechanische Reanimationshilfe etabliert. Eine orientierende Echokardiographie zeigte ein deutlich dilatiertes rechtes Herz. Ein NIRS-Monitoring wurde während der Reanimation nicht durchgeführt. In Zusammenschau mit einer weiterhin bestehenden PEA wurde die Verdachtsdiagnose der LAE gestellt. Das Team entschied sich zur Durchführung einer Thrombolyse mit Alteplase und alarmierte das ECPR-Team, das 53 min nach dem Reanimationsbeginn eine va-ECMO etablierte. Bei ausbleibendem ROSC wurde eine CT-Diagnostik durchgeführt; diese bestätigte die Diagnose einer LAE. Ein hämodynamisch relevanter Perikarderguss wurde unverzüglich drainiert und die Patientin auf eine Intensivstation verlegt.
Bei dort steigendem Vasopressorenbedarf trotz va-ECMO und sonographisch dargestellter freier abdomineller Flüssigkeit wurde die Patientin kurz darauf im hämorrhagischen Schock laparotomiert. Als Blutungsquelle fand sich ein blutender Uterus, sodass man sich zur Hysterektomie entschloss. Bei weiterhin bestehender Kreislaufinstabilität fand sich intraabdominell zusätzlich eine Leberlazeration entlang des Lig. falciforme, die operativ versorgt wurde. Nach Transfusion von 13 EK, 15 FFP, 7 TK, 2000 Einheiten PPSB, 2500 IE Faktor XIII sowie Fibrinogen (10 g) konnte die Patientin mit stabilisierten Kreislaufverhältnissen wieder auf die ICU verlegt werden. Im Verlauf der Behandlung zeigten sich am Folgetag beidseits lichtstarre Pupillen. Im cCT wurden ein generalisiertes Hirnödem und eine beginnende untere Einklemmung festgestellt. Bei infauster Prognose wurde mit den Angehörigen der Patientin eine Therapiezieländerung besprochen, und die Patientin verstarb am dritten postoperativen Tag
TRPM6 in murine kidneys-of targets and antibodies
Get PDFMagnesium is the fourth most abundant cation in the human organism. As a key-player in many enzymatic reactions, mag nesium homeostasis disbalance can cause severe disorders. In the early 2000s, the transient receptor potential melastatin
channel 6 (TRPM6) was identified as a critical protein in renal Mg2+-reabsorption in the distal convoluted tubule (DCT).
As the key-interface responsible for salt/water adaptation to environmental changes, the kidney is a highly dynamic system.
Therefore, renal TRPM6 expression and Mg2+-reabsorption might not be restricted to the DCT, as previously indicated. To
address this, protein targeting is mandatory since genomic detection is insufficient to conclude on functional expression.
For this purpose, we used a polyclonal TRPM6 antibody from an established manufacturer and detected immunostaining in
murine proximal and distal tubules. As a matter of fact, the specificity of most commercially available TRPM6 antibodies is
insufficiently validated which relies on the lack of constitutive trpm6 knockouts. Therefore, conditional trpm6 knockout mice
were used for control experiments. Similar signals were observed in the knockout tissue when compared to wildtype using the
TRPM6 antibody. Overlaps with TRPM7 epitopes or other peptides are conceivable. Thus, TRPM6 immunohistochemistry
and immunofluorescence results are difficult to interpret, and the spectrum of renal TRPM6 expression is not yet elucidated
Sex-Specific Properties of Astrocytes: From Development to Evolutionary Insights
Get PDFExploring sex-specific differences in astrocytes has emerged as a vital area of neurobiological research. This research sheds light on how astrocytes in females and males differ in their contribution to neuronal functionality, overall brain health, and various neurological disorders. These cells play a critical role in sustaining homeostasis, providing metabolic support, facilitating neurotransmitter recycling and responding to injuries to the central nervous system. Their physiology exhibits significant variability, which is influenced by factors such as sex, developmental stage, species differences and environmental conditions. This review provides an integrated overview of these factors, addressing key themes including developmental dynamics, aging, signalling mechanisms, glial interactions, responses to pathological states and cross-species comparisons
Assessment of cardiac biomarker "point-of-care" testing as postmortem diagnostic tool
Get PDFIn cardiac death, some entities, such as arrhythmia or nonocclusive myocardial ischemia, are not associated with clear and certain macroscopic surrogates of cardiac death. Cardiac biomarker point-of-care testing (POCT) seems suitable for further improving postmortem diagnostics in legal medicine casework. Considering the preanalytic phase, the present study aims to define criteria for blood samples suitable for POCT and assess the diagnostic performance of postmortem cardiac biomarker POCT. A fluorescent immunoassay device was used. The biomarkers assessed were myoglobin, brain-type natriuretic peptide (BNP), N-terminal proBNP, creatine kinase muscle-brain type, and cardiac troponin I. Blood was obtained from the intrapericardial inferior vena cava. In a prestudy, criteria for the selection of blood samples were established and the biomarker stability over time, test reliability and reproducibility of postmortem cardiac biomarker analyses were assessed. Afterward, blood samples from 150 autopsied individuals were evaluated for their diagnostic performance and compared with findings from autopsy as the postmortem diagnostic gold standard. In doing so, the assessed biomarkers provided valid and reproducible results. Cardiac troponin I yielded the highest sensitivity for detecting cardiac death, whereas BNP had the highest specificity and positive predictive value for detecting cardiac death. Markers of myocardial damage had better negative than positive predictive value. NT-proBNP and BNP POCT seem applicable to support diagnosis of death associated with congestive heart failure. Postmortem cardiac biomarker POCT results need to be interpreted in conjunction with all available information, i.e., autopsy findings, medical history, investigatory results, and other test results
Feature Extractor for Damage Localization on Composite-Overwrapped Pressure Vessel Based on Signal Similarity Using Ultrasonic Guided Waves
Get PDFHydrogen is one of the future green energy sources that could resolve issues related to
fossil fuels. The widespread use of hydrogen can be enabled by composite-overwrapped
pressure vessels for storage. It offers advantages due to its low weight and improved
mechanical performance. However, the safe storage of hydrogen requires continuous
monitoring. Combining ultrasonic guided waves with interpretable machine learning
provides a powerful tool for structural health monitoring. In this study, we developed a
feature extraction approach based on a similarity method that enables interpretability in
the proposed machine learning model for damage detection and localization in pressure
vessels. Furthermore, a systematic optimization was performed to explore and tune the
model’s parameters. This resulting model provides accurate damage localization and is
capable of detecting and localizing damage on hydrogen pressure vessels with an average
localization error of 2 cm and a classification accuracy of 96.5% when using quantized
classification. In contrast, binarized classification yields a higher accuracy of 99.5%, but
with a larger localization error of 6 cm
Case Report: "DEK::AFF2 fusion associated sinonasal carcinomas: a novel oncogenic driver and emerging therapeutic strategies"
Get PDFBackground: DEK::AFF2 fusion-associated carcinomas of the sinonasal tract are exceedingly rare, with fewer than 100 cases reported worldwide, but probably underrecognized. Recently classified by the WHO as a distinct provisional subtype of non-keratinizing squamous cell carcinoma, these tumors pose significant diagnostic and therapeutic challenges. Their histological resemblance to inverted papillomas and their bland histology in most cases often leads to misdiagnosis, while their aggressive behavior underscores the need for a tailored treatment approach.
Case presentation: We report two cases of DEK::AFF2 fusion-associated carcinomas managed at Saarland University Medical Center. The first case involved a 46-year-old woman who initially presented with recurrent sinonasal inverted papilloma, confirmed through multiple surgical interventions over nearly a decade. In 2023, reevaluation and genetic analysis revealed a DEK::AFF2 fusion. The patient demonstrated an exceptional response to three cycles of neoadjuvant gemcitabine and cisplatin, achieving complete remission on MRI restaging. This allowed a shift to definitive chemoradiotherapy, with sustained disease-free status confirmed by a PET-CT three months post-treatment in July 2024. The second case involved a 66-year-old woman presenting with recurrent inverted papilloma affecting the sinonasal and tympanic regions. Despite multiple surgeries, malignant transformation to invasive squamous cell carcinoma occurred, with lymph node metastasis and intracranial spread. A combined otolaryngological and neurosurgical approach was undertaken, but the disease progressed. The patient passed away in January 2020, with postmortem review of the prior histology and genetic analysis confirming DEK::AFF2 fusion carcinoma that showed bland-looking papilloma-like morphology in the initial specimens and later a high-grade cytology indicating biological progression to poorly differentiated carcinoma.
Conclusion: These cases highlight the aggressive nature of DEK::AFF2 fusion-associated carcinomas and the critical role of genetic profiling in diagnosis and management. The exceptional, first ever reported response to neoadjuvant chemotherapy in one case underscores the potential for personalized treatment strategies, warranting further investigation into targeted therapies for this rare malignancy
Cardiac dissection techniques for pathoanatomical research on myocardial hypertrophy and anatomical teaching
Get PDFBackground
Various cardiac dissection techniques are used in basic pathoanatomical research on cardiovascular diseases and anatomical teaching. In contrast, diagnostic routine techniques in pathology and legal medicine have subject-specific recommendations. However, these recommendations do not outline specific techniques for the determination of heart weight and myocardial hypertrophy. Thus, the present manuscript outlines cardiac dissection techniques that may be employed in pathoanatomic and autopsy-based research and anatomical teaching.
Methods
A narrative literature review and discussion of established cardiac dissection techniques for diagnostic routine (Short-Axis and Inflow-Outflow methods), anatomical teaching (combined Window and Base-of-Heart methods) and pathoanatomic research on myocardial hypertrophy (Fulton and Chamber Partition techniques).
Results
Cardiac dissection techniques such as the Fulton method allow an in-depth assessment of ventricular hypertrophy by capturing the weight of specific parts of the heart. Such techniques, which are outside current recommendations for diagnostic routine, are desirable for research purposes. The examples in this review show how different dissection techniques visualize different cardiac structures for anatomical teaching.
Conclusion
Various cardiac dissection techniques enable the in-depth assessment of myocardial hypertrophy and heart weight. For anatomical teaching, the simultaneous display of several dissection techniques improves visualization of cardiac structures and supports a better understanding of the topographic cardiac anatomy. In pathoanatomical research on cardiovascular diseases, certain dissection techniques beyond those employed in diagnostic routine improve the evaluation of myocardial hypertrophy and heart weight
Metabolic engineering of Corynebacterium glutamicum for increased cis, cis-muconate production from plant-derived p-hydroxycinnamates via deregulated pathway flux and increased CoA intermediate availability
Get PDFLignocellulosic biomass represents a promising renewable feedstock for sustainable biochemical production,
with p-hydroxycinnamates emerging as key aromatic building blocks derived from agricultural residues and
grassy plants. C. glutamicum has recently been engineered to produce cis, cis-muconate (MA), a high-value
platform chemical used in biobased plastics, resins, and specialty chemicals. However, unlike other aromatics,
the metabolism of the p-hydroxycinnamates p-coumarate, ferulate, and caffeate in MA-producing C. glutamicum is
inefficient, limiting MA production performance. Here, we discovered that p-hydroxycinnamate metabolism,
encoded by the phd operon, is repressed by the local repressor PhdR under glucose-rich conditions, while the
global regulator GlxR activates the pathway in the absence of glucose. The deregulated C. glutamicum MA-10
lacking phdR exhibited an up to 98-fold increase in the conversion of p-coumarate, ferulate, and aromatic
mixtures derived from plant waste into MA. Transcriptomic and metabolomic analyses revealed strong induction
of the phd operon in strain MA-10 and a marked increase in intracellular aromatic CoA-esters and acetyl-CoA,
indicating enhanced flux through the p-hydroxycinnamate degradation pathway. 13C-tracer studies demon strated a substantial contribution of aromatic side-chain carbon to central metabolic pathways, supporting
biomass formation and enabling MA production even in the absence of sugars. Additionally, MA-10 showed
broadened substrate flexibility, degrading cinnamate into MA and methoxylated cinnamates into valuable
benzoate derivatives. The strain also successfully converted aromatics from real straw lignin hydrolysates into
MA. Our findings reveal the potential of targeted regulatory engineering to optimize C. glutamicum for lignin
valorization. The newly developed strain MA-10 provides a robust platform for the biobased production of MA
from lignocellulosic feedstocks, paving the way for sustainable and economically viable biorefinery processes