Persisters are phenotypically antibiotic-tolerant cells which can survive antibiotic exposure without acquiring antibiotic resistance. A proposed important factor in persistence is low intracellular ATP levels, which are thought to reduce the activity of antibiotic targets. However, previous studies demonstrated that persisters have comparable DNA damage as drug-sensitive bacteria after fluoroquinolone treatment. Furthermore, recent studies reported that endogenous prophages can reduce levels of antibiotic persistence in Salmonella after fluoroquinolone treatment. In this study, we examined prophage induction and persister cell survival of a prophage-free variant of Salmonella Typhimurium and strains harbouring a deletion of the tisAB genes, with tisB encoding the toxin from the tisB/istR-1 toxin-antitoxin system, known to reduce the intracellular ATP concentration. Treatment of the prophage-free variant with ciprofloxacin resulted in reduced killing and increased persistence as compared to the wild type. In addition, prophage induction and prophage mediated killing was significantly increased after deletion of tisAB following ciprofloxacin treatment. We also demonstrate that the recovery phase following the removal of ciprofloxacin, is crucial for the induction of endogenous prophages. Our results suggest that ATP-dependent prophage activation plays a significant role in DNA damage-mediated killing of bacteria. Low ATP levels can dampen the induction of prophages and increase the fraction of bacterial survivors after ciprofloxacin treatment.

Alzheimer’s disease (AD) is one of the main causes of dementia, with an exponential increment in its incidence as years go by. However, since pathophysiological mechanisms are complex and multifactorial, therapeutic strategies remain inconclusive and only provide symptomatic relief to patients. In order to solve this problem, new strategies have been investigated over recent years for AD treatment. This field has been reborn due to epidemiological and preclinical findings that demonstrate the fact that omega-3 polyunsaturated fatty acids (ω-3 PUFAs) can be promising therapeutic agents because of their anti-inflammatory, antioxidant, and neurogenic-promoting activities, thus allowing us to classify these molecules as neuroprotectors. Similarly, ω-3 PUFAs perform important actions in the formation of characteristic AD lesions, amyloid-β plaques (Aβ) and neurofibrillary tangles, reducing the development of these structures. Altogether, the aforementioned actions hinder cognitive decline and possibly reduce AD development. In addition, ω-3 PUFAs modulate the inflammatory response by inhibiting the production of pro-inflammatory molecules and promoting the synthesis of specialised pro-resolving mediators. Consequently, the present review assesses the mechanisms by which ω-3 PUFAs can act as therapeutic molecules and the effectiveness of their use in patients. Clinical evidence so far has shown promising results on ω-3 PUFA effects, both in animal and epidemiological studies, but remains contradictory in clinical trials. More research on these molecules and their neuroprotective effects in AD is needed, as well as the establishment of future guidelines to obtain more reproducible results on this matter.

Malignant melanoma (MM) affects not only humans but also animals, with gray horses being particularly predisposed to acquiring the disease. Multiomics have greatly advanced the understanding of human MM. In contrasty little is known regarding the pathogenesis of gray-horse melanoma and the unique phenomenon of melanoma “dormancy” in some animals. To help close this gap in knowledge, melanoma tissue and intact skin collected from gray horses were subjected to transcriptome analysis using RNAseq. In the next step, cultured primary tumor cells and normal skin fibroblasts were established from gray horses, and their protein expression profiles were determined. The obtained data unambiguously identified gray-horse melanoma (ghM) as a malignant tumor, as reflected by the overrepresentation of pathways typically activated in human melanoma and other human cancers. These included the RAS/RAF/MAPK, the IRS/IGF1R, and the PI3K/AKT signaling networks. In addition, the obtained data suggest that the key molecules RAC1, RAS, and BRAF, which are frequently mutated in human melanoma, may also contain activating mutations in ghM, whilst PTEN may harbor loss-of-function mutations. This issue will be subject to downstream analyses determining the mutational status in ghM to further advance the understanding of this frequent disease in gray horses.

Background/Objectives: More than 33 billion chickens are industrially raised for meat and egg production globally and vaccinated against Marek’s disease virus (MDV). The antigenically related herpesvirus of turkey (HVT) is used as a live-attenuated vaccine, commonly provided as a recombinant vector to protect chickens against additional unrelated pathogens. Because HVT replicates in a strictly cell-associated fashion to low levels of infectious units, adherent primary chicken or duck embryo fibroblasts are infected, dislodged from the cultivation surface and distributed as cryocultures in liquid nitrogen to the site of application. Although viable cells are complex products, application of infected cells in ovo confers protection even in presence of maternal antibodies. Methods/Results: The aim of our study was to determine whether a continuous cell line in a scalable cultivation format can be used for production of HVT-based vaccines. The AGE1.CR cell line (from Muscovy duck) was found to be highly permissive in adherent cultures. Propagation in suspension, however, initially gave very low yields. The induction of cell-to-cell contacts in carrier-independent suspensions and a metabolic shock improved titers to levels suitable for vaccine production (>105 infectious units/mL after infection with multiplicity of 0.001). Conclusions: Production of HVT is challenging to scale to large volumes and the reliance on embryonated eggs from biosecure facilities is complex. We demonstrate that a cell-associated HVT vector can be propagated in a carrier-independent suspension culture of AGE1.CR cells in chemically defined medium. The fed-batch production is independent of primary cells and animal-derived material and can be scaled to large volumes.

Endogenous opioids, such as Endomorphin-2, are not typically associated with severe constipation, unlike pharmaceutical opioids, which induce opioid-induced constipation (OIC) by activating μ-opioid receptors in the gastrointestinal tract. In this study, we present a mathematical model, which integrates the serotonergic and opioid pathways, simulating the interaction between serotonin and opioid signaling within the enteric nervous system (ENS). The model explores the mechanisms underlying OIC, with a focus on the change in adenylyl cyclase (AC) activity, cAMP accumulation, and the distinct functionalities of Endomorphin-2 compared to commonly used pharmaceutical opioids. We study the effects of Morphine, Fentanyl, and Methadone and contrast them with Endomorphin-2. Our findings reveal that opioids do not perturb the signaling of serotonin, but only the activity of AC, suggesting that serotonin levels have no influence on improving opioid-induced constipation. Furthermore, this study reveals that the primary difference between endogenous and pharmaceutical opioids is their degradation rates. This finding shows that modulating opioid degradation rates significantly improves cAMP recovery. In conclusion, our insights steer towards exploring opioid degrading enzymes, localized to the gut, as a strategy for mitigating OIC.

The implementation of the position paper commissioned by the German Society for Social Psychiatry (DGSP) with the abolition of the criminal liability provisions ( 29, 21 German Criminal Code, StGB) and the psychiatric restriction orders ( 63, 64 StGB) would mean that in Germany the vast majority of mentally ill lawbreakers due to the seriousness of the initial offence, would now be imprisoned in penal institutions. Although there is experience in dealing with the mentally ill, they would have to fear a poorer quality of care and, in particular fewer chances of rehabilitation in prison for various reasons. From the author's point of view, instead of abolishing psychiatric restriction orders, more flexibility should be created and, to relieve the burden on psychiatric hospitals, a revitalization of the measure of placement in a social therapy institution, which has never come into force, whereby the measure of preventive detention could be abolished.

Echinococcosis is a life-threatening neglected zoonotic disease. Cystic echinococcosis (CE) due to Echinococcus (E.) granulosus usually involves livestock and dogs; alveolar echinococcosis (AE) due to E. multilocularis involves rodents and canines such as foxes and dogs. Human hosts are infected accidentally via hand to mouth and/or foodborne/waterborne pathways. Albania is deemed to be endemic for cystic echinococcosis (CE), but there is a scarcity of data to confirm this. A systematic literature search was performed in PubMed, Google Scholar, and in other medical sources. Because of the scarcity of existing information, data confirming CE cases were reviewed from the medical hospital records of Albania's largest Hospital, the Mother Teresa University Hospital (UHCMT) Tirana, and from a large private laboratory in Tirana (Pegasus laboratory). A total of eight eligible publications on 540 CE patients were found. Three hundred forty seven additional cases hospitalized in UHCMT from 2011 to 2020 were confirmed, as well as 36 laboratory cases and 10 Albanian cases notified in Germany. Taking all cases into account and considering 162 overlapping cases, 771 cases were documented from 2011 to 2020. The only case reported as AE was most likely a multi-organic CE. Surgery was the most frequent therapy approach used (84.7%). Autochthonous human CE seems to be widespread, and transmission is ongoing in Albania. CE patients in Albania undergo surgery more frequently compared with CE cases in other European countries. In order to establish a realistic estimate of prevalence and incidence of CE in Albania, mandatory notification should be reinforced. Stage-specific therapy can be used in CE to reduce therapy cost and diminish mortality by avoiding surgical overtreatment.

Intestinal barrier studies often employ cell lines having limited cell type representation compared to native tissue. Organoids comprising most intestinal cell types better mimic in vivo conditions. However, 3D organoids pose challenges for barrier analysis. Thus, organoid-derived monolayers were generated that closely resemble donor tissue under optimized conditions, making them suitable for tissue-specifi c investi gation. Further developments will incorporate additional intestinal compartments.

Objectives This study aimed to evaluate the influence of vestibuloplasty on the clinical success and survival of dental implants in head and neck tumor patients.Materials and methods A retrospective single-center study was conducted. All patients received surgical therapy of a tumor in the head or neck and underwent surgical therapy and, if necessary, radiotherapy/radiochemotherapy. Patients with compromised soft tissue conditions received vestibuloplasty using a split thickness skin graft and an implant-retained splint. Implant survival and success and the influence of vestibuloplasty, gender, radiotherapy, and localizations were evaluated.Results A total of 247 dental implants in 49 patients (18 women and 31 men; mean age of 63.6 years) were evaluated. During the observation period, 6 implants were lost. The cumulative survival rate was 99.1% after 1 year and 3 years and 93.1% after 5 years for patients without vestibuloplasty, compared to a survival and success rate of 100% after 5 years in patients with vestibuloplasty. Additionally, patients with vestibuloplasty showed significantly lower peri-implant bone resorption rates after 5 years (mesial: p = 0.003; distal: p = 0.001).Conclusion This study demonstrates a high cumulative survival and success rate of dental implants after 5 years in head and neck tumor patients, irrespective of irradiation. Patients with vestibuloplasty showed a significantly higher rate of implant survival and significantly lower peri-implant bone resorption after 5 years.

Background: With the Chronic Ear Survey (CES), a validated measurement instrument for the assessment of disease-specific health-related quality of life (HRQoL) has been available internationally since 2000. The aim of this study was to provide a validated German version of this international instrument and to compare it with the German Chronic Otitis Media Outcome Test 15 (COMOT-15). Methodology: The CES was translated into German via a forward-backward translation process. For validation, 79 patients with COM undergoing middle ear surgery were prospectively included. HRQoL was determined preoperatively and 6 months postoperatively using the CES and the COMOT-15. Pure tone audiometry was also performed at both measurement time points. In the control examination, an additional retrospective assessment of the preoperative situation was additionally performed using the CES and the COMOT-15 to assess the response shift. The determined psychometric characteristics were internal consistency, test-retest reliability, discrimination validity, agreement validity, responsiveness, and response shift for both measurement instruments. Convergent validity of both measurement instruments was assessed using linear regression. Results: On the basis of the CES, patients with COM could be reliably distinguished from patients with healthy ears. The CES showed satisfactory reliability with high internal consistency (Cronbach a 0.65-0.85) and high retest reliability (r> 0.8). The global assessment of HRQoL impairment correlated very well with the scores of the CES (r= 0.51). In addition, it showed a high sensitivity to change (standardized response mean -0.86). Compared to the COMOT-15, it showed a lower response shift (effect size -0.17 vs. 0.44). Both measurement instruments correlated only slightly with air conduction hearing threshold (r= 0.29 and r= 0.24, respectively). The concordant validity of both measurement instruments was high (r= 0.68). Conclusion: The German version of the CES shows satisfactory psychometric characteristics, so that its use can be recommended. The CES focuses on the influence of ear symptoms on HRQoL, whereas the COMOT-15 also includes functional and psychological aspects. Due to only minor response shift effects, the CES is particularly suitable for studies with multiple repeat measurements.

Background Spinal function can be assessed through different patient reported outcome measures (PROMs). Purpose: The aim of the present study was to evaluate a novel single-item score for the assessment of spinal function: The Subjective Spine Value (SSpV). It was hypothesized that the SSpV correlates with the established scores Oswestry disability index (ODI) and Core Outcome Measures Index (COMI).Methods Between 08/2020 and 11/2021 151 consecutive patients were prospectively enrolled and completed a questionnaire with the ODI, COMI as well as the SSpV. Patients were divided into 4 groups depending on their specific pathology (Group 1: Degenerative pathologies, Group 2: Tumor, Group 3: Inflammatory / Infection, Group 4: Trauma). Pearson correlation coefficient was used to evaluate correlation between the SSpV and the ODI and COMI separately. Floor and ceiling effects were evaluated.Results Overall, the SSpV correlated significantly with both ODI (p = < 0.001; r = - 0.640) and COMI (p = < 0.001; r = - 0.640). This was also observed across all investigated groups (range - 0.420-0.736). No relevant floor or ceiling effects were noticed.Conclusions The SSpV is a valid single-item score for the assessment of spinal function. The SSpV offers a useful tool to efficiently assess spinal function in a variety of spinal pathologies.

Background: With the Chronic Ear Survey (CES), a validated measurement instrument for the assessment of disease-specific health-related quality of life (HRQoL) has been available internationally since 2000. The aim of this study was to provide a validated German version of this international instrument and to compare it with the German Chronic Otitis Media Outcome Test 15 (COMOT-15). Methodology: The CES was translated into German via a forward-backward translation process. For validation, 79 patients with COM undergoing middle ear surgery were prospectively included. HRQoL was determined preoperatively and 6 months postoperatively using the CES and the COMOT-15. Pure tone audiometry was also performed at both measurement time points. In the control examination, an additional retrospective assessment of the preoperative situation was additionally performed using the CES and the COMOT-15 to assess the response shift. The determined psychometric characteristics were internal consistency, test-retest reliability, discrimination validity, agreement validity, responsiveness, and response shift for both measurement instruments. Convergent validity of both measurement instruments was assessed using linear regression. Results: On the basis of the CES, patients with COM could be reliably distinguished from patients with healthy ears. The CES showed satisfactory reliability with high internal consistency (Cronbach a 0.65-0.85) and high retest reliability (r>0.8). The global assessment of HRQoL impairment correlated very well with the scores of the CES (r = 0.51). In addition, it showed a high sensitivity to change (standardized response mean -0.86). Compared to the COMOT-15, it showed a lower response shift (effect size -0.17 vs. 0.44). Both measurement instruments correlated only slightly with air conduction hearing threshold (r = 0.29 and r = 0.24, respectively). The concordant validity of both measurement instruments was high (r= 0.68). Conclusion: The German version of the CES shows satisfactory psychometric characteristics, so that its use can be recommended. The CES focuses on the influence of ear symptoms on HRQoL, whereas the COMOT-15 also includes functional and psychological aspects. Due to only minor response shift effects, the CES is particularly suitable for studies with multiple repeat measurements.

Purpose Risk scores for community-acquired pneumonia (CAP) are widely used for standardized assessment in immunocompetent patients and to identify patients at risk for severe pneumonia and death. In immunocompromised patients, the prognostic value of pneumonia-specific risk scores seems to be reduced, but evidence is limited. The value of different pneumonia risk scores in kidney transplant recipients (KTR) is not known.Methods Therefore, we retrospectively analyzed 310 first CAP episodes after kidney transplantation in 310 KTR. We assessed clinical outcomes and validated eight different risk scores (CRB-65, CURB-65, DS-CRB-65, qSOFA, SOFA, PSI, IDSA/ATS minor criteria, NEWS-2) for the prognosis of severe pneumonia and in-hospital mortality. Risk scores were assessed up to 48 h after admission, but always before an endpoint occurred. Multiple imputation was performed to handle missing values.Results In total, 16 out of 310 patients (5.2%) died, and 48 (15.5%) developed severe pneumonia. Based on ROC analysis, sequential organ failure assessment (SOFA) and national early warning score 2 (NEWS-2) performed best, predicting severe pneumonia with AUC of 0.823 (0.747-0.880) and 0.784 (0.691-0.855), respectively.Conclusion SOFA and NEWS-2 are best suited to identify KTR at risk for the development of severe CAP. In contrast to immunocompetent patients, CRB-65 should not be used to guide outpatient treatment in KTR, since there is a 7% risk for the development of severe pneumonia even in patients with a score of zero.

Objectives The use of remdesivir (RDV) as the first drug approved for coronavirus disease 2019 (COVID-19) remains controversial. Based on the Lean European Open Survey on severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infected patients (LEOSS), we aim to contribute timing-focused complementary real-world insights to its evaluation.Methods SARS-CoV-2 infected patients between January 2020 and December 2021 treated with RDV were matched 1:1 to controls considering sociodemographics, comorbidities and clinical status. Multiple imputations were used to account for missing data. Effects on fatal outcome were estimated using uni- and multivariable Cox regression models.Results We included 9,687 patients. For those starting RDV administration in the complicated phase, Cox regression for fatal outcome showed an adjusted hazard ratio (aHR) of 0.59 (95%CI 0.41-0.83). Positive trends could be obtained for further scenarios: an aHR of 0.51 (95%CI 0.16-1.68) when RDV was initiated in uncomplicated and of 0.76 (95% CI 0.55-1.04) in a critical phase of disease. Patients receiving RDV with concomitant steroids exhibited a further reduction in aHR in both, the complicated (aHR 0.50, 95%CI 0.29-0.88) and critical phase (aHR 0.63, 95%CI 0.39-1.02).Conclusion Our study results elucidate that RDV use, in particular when initiated in the complicated phase and accompanied by steroids is associated with improved mortality. However, given the limitations of non-randomized trials in estimating the magnitude of the benefit of an intervention, further randomized trials focusing on the timing of therapy initiation seem warranted.

Most mental disorders have a typical onset between 12 and 25 years of age, highlighting the importance of this period for the pathogenesis, diagnosis, and treatment of mental ill-health. This perspective addresses interactions between risk and protective factors and brain development as key pillars accounting for the emergence of psychopathology in youth. Moreover, we propose that novel approaches towards early diagnosis and interventions are required that reflect the evolution of emerging psychopathology, the importance of novel service models, and knowledge exchange between science and practitioners. Taken together, we propose a transformative early intervention paradigm for research and clinical care that could significantly enhance mental health in young people and initiate a shift towards the prevention of severe mental disorders.

In the absence of randomized controlled trials comparing tisagenlecleucel vs. standard of care (SOC) in pediatric and young adult patients with relapsed or refractory acute lymphoblastic leukemia (r/r ALL), the objective was to compare the efficacy of tisagenlecleucel with historical controls from multiple disease registries using patient-level adjustment of the historical controls. The analysis is based on patient-level data of three tisagenlecleucel studies (ELIANA, ENSIGN and CCTL019B2001X) vs. three registries in Germany/Austria. Statistical analyses were fully pre-specified and propensity score weighting of the historical controls by fine stratification weights was used to adjust for relevant confounders identified by systematic literature review. Results showed high comparability of cohorts after adjustment with absolute SMD <= 0.1 for all pre-specified confounders and favorable outcomes for tisagenlecleucel compared to SOC for all examined endpoints. Hazard ratios for OS(Intention to treat)ITT,adjusted, EFS(Full analysis set)FAS,na & iuml;ve and RFSFAS,na & iuml;ve were 0.54 (95% CI: 0.41-0.71, p < 0.001), 0.67 (0.52-0.86, p = 0.001) and 0.77 (0.51-1.18, p = 0.233). The OSITT, adjusted, EFSFAS,na & iuml;ve and RFSFAS,naive survival probability at 2 years was 59.49% for tisagenlecleucel vs. 36.16% for SOC population, 42.31% vs. 30.23% and 59.60% vs. 54.57%, respectively. Odds ratio for ORRITT,adjusted was 1.99 (1.33-2.97, p < 0.001). Results for OS and ORR were statistically significant after adjustment for confounders and provide evidence supporting a superiority of tisagenlecleucel in r/r ALL given the good comparability of cohorts after adjustment for confounders.

Background Both obesity hypoventilation syndrome (OHS) and opium dependence can negatively affect nocturnal respiratory functionality. However, the effects of a combination of the two are relatively unknown. In this study, the tidal volume (VT) of OHS patients with and without opium dependence was estimated by measuring changes in the circumference of the thorax and the abdomen during sleep.Materials and methods This case-control study was performed in Iran, Isfahan. Initially, 20 healthy subjects calibrated the Pneumobelts (Lowenstein Medical Technology GmbH, Hamburg, Germany) by wearing the device and also breathing in and out of a Spirobag. From this, it was possible to estimate the coefficient factors for determining VT based on thoracic and abdominal measures. Subsequently, the study included 55 patients with OHS, who were divided into two groups: opium dependent and non-users. They were then admitted to the sleep lab for a single night of polysomnography (PSG). VT was estimated and then compared between groups.Results In total, there were 24 patients in the opium group and 31 in the non-user control group. All PSG variables were analyzed with independent-sample t-tests and an analysis of covariance was used to adjust for potential confounding variables. The following confounding variables were adjusted: sex, smoking, body mass index, and hypertension. VT values were not significantly different between groups (opium: 772 +/- 125.4; non-user: 774 +/- 95). Average oxygen saturation values were significantly lower in opium-dependent patients (opium: 86.1 +/- 5.5; non-user: 89.1 +/- 4.1). All other variables from PSG including chest and abdominal circumference were not significantly different between groups.Conclusion OHS patients with opium dependency showed similar VT levels when compared to non-users with OHS. Due to the rarity of the sample, it was difficult to gather exactly matched pairs. Therefore, it is possible that with a more closely related sample, we might be able to see a difference in VT between groups.

Diagnosing pedohebephilia is fraught with obstacles given the tabooed nature of this sexual preference. The viewing reaction time effect (VRT) provides a non-intrusive indirect measure of sexual interest in minors. In forensic populations, the ability of the difference between the latencies while viewing child and adult sexual stimuli (VRT index) to discern child sexual offenders from a range of control groups has been ascertained meta-analytically. Given that the effect has been studied almost exclusively in forensic samples, its dependence or independence on prior overt (deviant) sexual behavior remains unclear. The present study sought to examine the relationship of prior sexual and non-sexual behaviors with the VRT in a sample of 282 self-referring, help-seeking men with and without pedohebephilia with and without a history of prior child sexual offenses (CSO) or a use of child sexual abuse materials (CSAM) recruited outside a forensic context. We found that (1) the clinical diagnosis of pedohebephilia but not prior CSO or CSAM showed a significant association with the VRT index; (2) the discriminatory ability of the VRT index did not differ significantly between samples with and without a history of prior overt sexual behavior with children; (3) the VRT index correlated positively with a behavioral marker of pedohebephilia in a subsample of individuals with prior judicially detected or undetected overt sexual behavior with children; and (4) in the same subsample, the VRT index correlated positively with markers of sexual interests in minors or hypersexuality but not of antisociality. Equivalence testing failed to refute a potential effect of prior sexual behavior on the VRT index. Our study showed that the VRT may provide an unintrusive diagnostic tool for pedohebephilia. The effect of prior overt sexual behavior with children needs further examination.

Recent investigations analyzed in depth the biochemical and biophysical properties of the endothelial glycocalyx. In comparison, this complex cell-covering structure is largely understudied in alveolar epithelial cells. To better characterize the alveolar glycocalyx ultrastructure, unaffected versus injured human lung tissue explants and mouse lungs were analyzed by transmission electron microscopy. Lung tissue was treated with either heparinase (HEP), known to shed glycocalyx components, or pneumolysin (PLY), the exotoxin of Streptococcus pneumoniae not investigated for structural glycocalyx effects so far. Cationic colloidal thorium dioxide (cThO(2)) particles were used for glycocalyx glycosaminoglycan visualization. The level of cThO(2) particles orthogonal to apical cell membranes ( estimates stained glycosaminoglycan height) of alveolar epithelial type I (AEI) and type II (AEII) cells was stereologically measured. In addition, cThO(2) particle density was studied by dual-axis electron tomography ( estimates stained glycosaminoglycan density in three dimensions). For untreated samples, the average cThO(2) particle level was & AP; 18 nm for human AEI, & AP; 17 nm for mouse AEI, ≈ AP; 44 nm for human AEII and ≈ AP; 35 nm for mouse AEII. Both treatments, HEP and PLY, resulted in a significant reduction of cThO(2) particle levels on human and mouse AEI and AEII. Moreover, a HEP- and PLY-associated reduction in cThO(2) particle density was observed. The present study provides quantitative data on the differential glycocalyx distribution on AEI and AEII based on cThO(2) and demonstrates alveolar glycocalyx shedding in response to HEP or PLY resulting in a structural reduction in both glycosaminoglycan height and density. Future studies should elucidate the underlying alveolar epithelial cell type-specific distribution of glycocalyx subcomponents for better functional understanding.

Purpose: This study sought to investigate the role of radiotherapy (RT) in addition to surgery for oncological outcomes in patients with malignant peripheral nerve sheath tumors (MPNST).Methods: In this single-center, retrospective cohort study, histopathologically confirmed MPNST were analyzed. Local control (LC), overall survival (OS), and distant metastasis-free survival (DMFS) were assessed using the Kaplan-Meier estimator. Multivariable Cox regression analysis was performed to identify factors associated with LC, OS, and DMFS.Results: We included 57 patients with a median follow-up of 20.0 months. Most MPNSTs were located deeply (87.5%), were larger than 5 cm (55.8%), and had high-grade histology (78.7%). Seventeen patients received surgery only, and 25 patients received surgery and pre- or postoperative RT. Median LC, OS, and DMFS after surgery only were 8.7, 25.5, and 22.0 months; after surgery with RT, the median LC was not reached, while the median OS and DMFS were 111.5 and 69.9 months. Multivariable Cox regression of LC revealed a negative influence of patients presenting with local disease recurrence compared to patients presenting with an initial primary diagnosis of localized MPNST (hazard ratio: 8.86, p = 0.003).Conclusions: The addition of RT to wide surgical excision appears to have a beneficial effect on LC. Local disease recurrence at presentation is an adverse prognostic factor for developing subsequent local recurrences. Future clinical and translational studies are warranted to identify molecular targets and find effective perioperative combination therapies with RT to improve patient outcomes.