The spine-brain axis: is spinal anatomy associated with brain volume?

First small sample studies indicate that disturbances of spinal morphology may impair craniospinal flow of cerebrospinal fluid and result in neurodegeneration. The aim of this study was to evaluate the association of cervical spinal canal width and scoliosis with grey matter, white matter, ventricular and white matter hyperintensity volumes of the brain in a large study sample. Four hundred participants underwent whole-body 3 T magnetic resonance imaging. Grey matter, white matter and ventricular volumes were quantified using a warp-based automated brain volumetric approach. Spinal canal diameters were measured manually at the cervical vertebrae 2/3 level. Scoliosis was evaluated using manual measurements of the Cobb angle. Linear binomial regression analyses of measures of brain volumes and spine anatomy were performed while adjusting for age, sex, hypertension, cholesterol levels, body mass index, smoking and alcohol consumption. Three hundred eighty-three participants were included [57% male; age: 56.3 (±9.2) years]. After adjustment, smaller spinal canal width at the cervical vertebrae 2/3 level was associated with lower grey matter (P = 0.034), lower white matter (P = 0.012) and higher ventricular (P = 0.006, inverse association) volume. Participants with scoliosis had lower grey matter (P = 0.005), lower white matter (P = 0.011) and larger brain ventricular (P = 0.003) volumes than participants without scoliosis. However, these associations were attenuated after adjustment. Spinal canal width at the cervical vertebrae 2/3 level and scoliosis were not associated with white matter hyperintensity volume before and after adjustment (P > 0.864). In our study, cohort smaller spinal canal width at the cervical vertebrae 2/3 level and scoliosis were associated with lower grey and white matter volumes and larger ventricle size. These characteristics of the spine might constitute independent risk factors for neurodegeneration.

Determinants of long-term survival in patients with IDH-mutant gliomas.

BACKGROUND: Survival times of patients with IDH-mutant gliomas are variable and can extend to decades. Many studies provide progression-free rather than overall survival times and prognostic factors remain ill-defined. Here we explored characteristics of short- and long-term survivors within a cohort of patients with extended follow-up. METHODS: This single-center, case-control study included 86 patients diagnosed between 1998 and 2023 who either died within 6 years after diagnosis or survived at least 15 years. Patient characteristics and prognostic factors were stratified by short- (< 6 years) versus long-term (≥ 15 years) survival. RESULTS: Forty-seven patients (55%) diagnosed with astrocytoma and 39 patients (45%) with oligodendroglioma were included retrospectively. Median follow-up of the survivors was 16.6 years (range 15-28.9). Thirty-four deaths (40%) had been reported at database closure. Long-term survival was associated with CNS WHO grade 2 (p < 0.01), smaller tumor volumes (p = 0.01), lack of contrast enhancement (p < 0.01), wait-and-scan strategies (p < 0.01) and female sex (p = 0.04). In multivariate analyses for oligodendroglioma, larger T2 tumor volumes were associated with shorter survival (HR 1.02; 95% CI 1.01-1.05; p = 0.04). In patients with astrocytoma, lack of contrast enhancement (HR 0.38; 95% CI 0.15-0.94; p = 0.04) and wait-and-scan strategies (HR 5.75; 95% CI 1.66-26.61; p = 0.01) were associated with longer survival. CONCLUSION: Large T2 tumor volume and contrast enhancement may be important risk factors for shorter survival, while age might be of lesser importance. Wait-and-scan strategies may yield excellent long-term survival in some patients with astrocytoma.

Accuracy of the Bedside Examination in Patients With Suspected Acute Unilateral Peripheral Vestibulopathy.

OBJECTIVE: Acute unilateral peripheral vestibulopathy (AUPVP) is a frequent form of peripheral vestibular vertigo characterized by unilateral vestibular organ dysfunction. Diagnostic challenges in anamnesis and bedside examination can lead to potential misdiagnoses. This study investigated the sensitivity of bedside examinations in diagnosing AUPVP. METHODS: This retrospective analysis examined 136 AUPVP inpatients at a level 3 university hospital between 2017 and 2019. Demographic data and bedside test results were collected. Instrumental otoneurological tests included caloric testing and video head impulse test (HIT). The sensitivity of each bedside parameter was computed based on the instrumental diagnostics, and statistical analyses were performed. RESULTS: The study included 76 men and 60 women, with a mean age of 59.2 years. Spontaneous nystagmus exhibited a sensitivity of 92%, whereas the absence of skew deviation was identified with a sensitivity of 98%. Abnormal bedside HIT showed a sensitivity of 87%. The combined HINTS (HIT, nystagmus, and test of skew) had a sensitivity of 83%. The Romberg test and Fukuda test demonstrated sensitivities of 26% and 48%, respectively. CONCLUSION: The sensitivity of bedside tests varied from 26% to 98%. This aligns with previous literature, highlighting the challenge of differentiating AUPVP from vestibular pseudoneuritis solely through bedside examination. Although the tests excel in excluding central causes, they are insufficient for diagnosing AUPVP with certainty. In addition, the bedside examination sensitivities vary widely, and early radiological imaging can be misleading. Therefore, this study underlines the necessity of prompt otoneurological testing for accurate exclusion of vestibular pseudoneuritis and thus improve patient outcomes.

The evolutionary and ecological significance of phylloclade formation: A morpho-anatomical approach.

Instead of leaves, in a few species the main photosynthetic organ is a flattened structure that can be a modified branch (e.g. Ruscus, Jacksonia) or a fused combination of branch and leaf tissue (e.g. Phyllocladus) called a phylloclade. The phylloclades of Phyllocladus lack xeromorphic features in their wet habitat. They are broad under the low light conditions as are those of Ruscus which can occur in forest understories. However Ruscus is also common in dry habitats and shows numerous xeromorphic features. In Jacksonia extensive sclerenchyma and thick cuticle protect the phylloclades from desiccation damage in xeric seasonal conditions. Despite former contrary definitions of phylloclades we advocate they be defined as pseudo-petiolate organs determinate in growth which arise from axillary buds in the axil of reduced leaves and resemble a leaf.

Evaluation of surgical treatment strategies and outcome for cerebral arachnoid cysts in children and adults.

OBJECTIVE: The best treatment strategies for cerebral arachnoid cysts (CAC) are still up for debate. In this study, we present CAC management, outcome data, and risk factors for recurrence after surgical treatment, focusing on microscopic/endoscopic approaches as compared to minimally invasive stereotactic procedures in children and adults. METHODS: In our single-institution retrospective database, we identified all patients treated surgically for newly diagnosed CAC between 2000 and 2022. Microscopic/endoscopic surgery (ME) aimed for safe cyst wall fenestration. Stereotactic implantation of an internal shunt catheter (STX) to drain CAC into the ventricles and/or cisterns was used as an alternative procedure in patients aged ≥ 3 years. Treatment decisions in favor of ME vs. STX were made by interdisciplinary consensus. The primary study endpoint was time to CAC recurrence (TTR). Secondary endpoints were outcome metrics including clinical symptoms and MR-morphological analyses. Data analysis included subdivision of the total cohort into three distinct age groups (AG1, < 6 years; AG2, 6-18 years; AG3, ≥ 18 years). RESULTS: Sixty-two patients (median age 26.5 years, range 0-82 years) were analyzed. AG1 included 15, AG2 10, and AG3 37 patients, respectively. The main presenting symptoms were headache and vertigo. In AG1 hygromas, an increase in head circumference and thinning of cranial calvaria were most frequent. Thirty-five patients underwent ME and 27 STX, respectively; frequency did not differ between AGs. There were two (22.2%) periprocedural venous complications in infants (4- and 10-month-old) during an attempt at prepontine fenestration of a complex CAC, one with fatal outcome in a 10-month-old boy. Other complications included postoperative bleeding (2, 22.2%), CSF leaks (4, 44.4%), and meningitis (1, 11.1%). Overall, clinical improvement and significant volume reduction (p = 0.008) were seen in all other patients; this did not differ between AGs. Median follow-up for all patients was 25.4 months (range, 3.1-87.1 months). Recurrent cysts were seen in 16.1%, independent of surgical procedure used (p = 0.7). In cases of recurrence, TTR was 7.9 ± 12.7 months. Preoperative ventricular expansion (p = 0.03), paresis (p = 0.008), and age under 6 years (p = 0.03) were significant risk factors for CAC recurrence in multivariate analysis. CONCLUSIONS: In patients suffering from CAC, both ME and STX can improve clinical symptoms at low procedural risk, with equal extent of CAC volume reduction. However, in infants and young children, CAC are more often associated with severe clinical symptoms, stereotactic procedures have limited use, and microsurgery in the posterior fossa may bear the risk of severe venous bleeding.

Strong Association of Depression and Anxiety With the Presence of Back Pain While Impact of Spinal Imaging Findings is Limited: Analysis of an MRI Cohort Study.

Development of back pain is multifactorial, and it is not well understood which factors are the main drivers of the disease. We therefore applied a machine-learning approach to an existing large cohort study data set and sought to identify and rank the most important contributors to the presence of back pain amongst the documented parameters of the cohort. Data from 399 participants in the KORA-MRI (Cooperative health research in the region Augsburg-magnetic resonance imaging) (Cooperative Health Research in the Region Augsburg) study was analyzed. The data set included MRI images of the whole body, including the spine, metabolic, sociodemographic, anthropometric, and cardiovascular data. The presence of back pain was one of the documented items in this data set. Applying a machine-learning approach to this preexisting data set, we sought to identify the variables that were most strongly associated with back pain. Mediation analysis was performed to evaluate the underlying mechanisms of the identified associations. We found that depression and anxiety were the 2 most selected predictors for back pain in our model. Additionally, body mass index, spinal canal width and disc generation, medium and heavy physical work as well as cardiovascular factors were among the top 10 most selected predictors. Using mediation analysis, we found that the effects of anxiety and depression on the presence of back pain were mainly direct effects that were not mediated by spinal imaging. In summary, we found that psychological factors were the most important predictors of back pain in our cohort. This supports the notion that back pain should be treated in a personalized multidimensional framework. PERSPECTIVE: This article presents a wholistic approach to the problem of back pain. We found that depression and anxiety were the top predictors of back pain in our cohort. This strengthens the case for a multidimensional treatment approach to back pain, possibly with a special emphasis on psychological factors.

Functional connectivity MRI provides an imaging correlate for chimeric antigen receptor T-cell-associated neurotoxicity.

Background: Treatment of hematological malignancies with chimeric antigen receptor modified T cells (CART) is highly efficient, but often limited by an immune effector cell-associated neurotoxicity syndrome (ICANS). As conventional MRI is often unremarkable during ICANS, we aimed to examine whether resting-state functional MRI (rsfMRI) is suitable to depict and quantify brain network alterations underlying ICANS in the individual patient. Methods: The dysconnectivity index (DCI) based on rsfMRI was longitudinally assessed in systemic lymphoma patients and 1 melanoma patient during ICANS and before or after clinical resolution of ICANS. Results: Seven lymphoma patients and 1 melanoma patient (19-77 years; 2 female) were included. DCI was significantly increased during ICANS with normalization after recovery (P = .0039). Higher ICANS grades were significantly correlated with increased DCI scores (r = 0.7807; P = .0222). DCI increase was most prominent in the inferior frontal gyrus and the frontal operculum (ie, Broca's area) and in the posterior parts of the superior temporal gyrus and the temporoparietal junction (ie, Wernicke's area) of the language-dominant hemisphere, thus reflecting the major clinical symptoms of nonfluent dysphasia and dyspraxia. Conclusions: RsfMRI-based DCI might be suitable to directly quantify the severity of ICANS in individual patients undergoing CAR T-transfusion. Besides ICANS, DCI seems a promising diagnostic tool to quantify functional brain network alterations during encephalopathies of different etiologies, in general.

Detailed Seed Cone Morpho-Anatomy Provides New Insights into Seed Cone Origin and Evolution of Podocarpaceae; Podocarpoid and Dacrydioid Clades.

The study of reproductive morphology and trait evolution provides a vital insight to understand the evolutionary history of plants. The conifer family Podocarpaceae has a remarkable diversity of seed cones, with distinct morphology among the genera and with conifers in general. However, we lack a good understanding of the seed cone morpho-anatomy and trait evolution of Podocarpaceae. We investigated detailed seed cone morpho-anatomy using staining and sectioning techniques to clarify the anatomical, morphological diversity and evolution of functional traits. The presence of a fleshy receptaculum is a characteristic feature of both clades. However, species of Retrophyllum, Afrocarpus and some species of Nageia and Podocarpus form a fleshy sarcotesta-like seed coat, lacking a fleshy receptaculum. The ancestral state reconstructions show a shift between and sometimes within the genus. Although both clades demonstrate fleshiness as an ancestral trait, the shift in fleshy structures provides evidence for complex multiple evolutions of fleshy morphologies. These seed cone traits (e.g., fleshiness and size), along with the broad, flattened and well-adapted (leaf dimorphism) foliage in both clades, are largely congruent with efficient light harvesting and bird dispersal. These traits make these two clades well adapted to their environment, when growing in communities including tall and broad-leaved angiosperms (closed-canopy angiosperm forests), compared to other podocarps, making them more successful in achieving a wider distribution and species richness.

Prognostic factors in surgically treated malignant salivary gland tumors.

OBJECTIVES: To identify prognostic factors for evidence-based risk stratification in malignant salivary gland tumors. METHODS: This retrospective study identified 162 patients who presented with malignant salivary gland tumors between 2010 and 2020. Final analysis included 91 patients who underwent surgical treatment at our institution and were followed-up for ≥ 1 year. Medical records were reviewed and patients were categorized according to their risk profile. RESULTS: This study included 91 patients (51 males, 40 females, mean age 61 years). The most frequent entities were adenoid cystic carcinoma (n = 13, 14.3%) and mucoepidermoid carcinoma (n = 12, 13.2%). Kaplan-Meier analysis demonstrated a five-year overall survival (OS) of 66.2% and a recurrence-free survival (RFS) of 50.5%. Age > 60 years (p = 0.011), categorization into high-risk group (p = 0.011), UICC stage (p = 0.020), T stage (p = 0.032), grading (p = 0.045) and vascular invasion (p < 0.001) were significantly associated with OS; age > 60 years (p = 0.014), categorization into high-risk group (p < 0.001), UICC stage (p = 0.021), T stage (p = 0.017), grading (p = 0.011), vascular invasion (p = 0.012) and lymphovascular invasion (p < 0.001) were significantly associated with RFS. Multivariate Cox regression with backward elimination identified T stage (HR 1.835; 95% CI 1.187-2.836; p = 0.006) and grading (HR 2.233; 95% CI 1.113-4.480; p = 0.024) as significant factors for OS. Grading (HR 2.499; 95% CI 1.344-4.648; p = 0.004) was confirmed as a significant factor for RFS. CONCLUSION: Considering the risk of recurrence and distant metastasis in malignant salivary gland tumors, locoregional surgical control may not be sufficient and adjuvant therapies such as radiotherapy and/or systemic therapies should be considered.

Treatment benefit in patients aged 80 years or older with biopsy-proven and non-resected glioblastoma is dependent on MGMT promoter methylation status.

PURPOSE: Glioblastoma is associated with especially poor outcome in the elderly. It is unclear if patients aged ≥80 years benefit from tumor-specific therapy as opposed to receiving best supportive care (BSC) only. METHODS: Patients with IDH-wildtype glioblastoma (WHO 2021), aged ≥80 years, and diagnosed by biopsy between 2010 and 2022 were included. Patient characteristics and clinical parameters were assessed. Uni- and multivariate analyses were performed. RESULTS: 76 patients with a median age of 82 (range 80-89) and a median initial KPS of 80 (range 50-90) were included. Tumor-specific therapy was initiated in 52 patients (68%). 22 patients (29%) received temozolomide monotherapy, 23 patients (30%) were treated with radiotherapy (RT) alone and 7 patients (9%) received combination therapies. In 24 patients (32%), tumor-specific therapy was omitted in lieu of BSC. Overall survival (OS) was longer in patients receiving tumor-specific therapy (5.4 vs. 3.3 months, p < 0.001). Molecular stratification showed that the survival benefit was owed to patients with MGMT promoter methylation (MGMTpos) who received tumor-specific therapy as opposed to BSC (6.2 vs. 2.6 months, p < 0.001), especially to those with better clinical status and no initial polypharmacy. Patients with unmethylated MGMT promoter (MGMTneg) did not benefit from tumor-specific therapy (3.6 vs. 3.7 months, p = 0.18). In multivariate analyses, better clinical status and MGMT promoter methylation were associated with prolonged survival (p < 0.01 and p = 0.01). CONCLUSION: Benefit from tumor-specific treatment in patients with newly diagnosed glioblastoma aged ≥80 years might be restricted to MGMTpos patients, especially to those with good clinical status and no polypharmacy.

[Demographic and epidemiological risk factors in patients with acute vestibular neuritis]. / Demografische und epidemiologische Risikofaktoren bei Patienten mit akuter unilateraler Vestibulopathie M. Menière (hydropische Innenohrerkrankung).

OBJECTIVE: Vestibular neuritis (VN) is one of the most common peripheral vestibular balance disorder. Demographic and other risk factors associated with VN are insufficiently published. Therefore, the aim of this study is to identify associated risk factors in patients with acute VN. METHODS: This study evaluated all hospitalized VN cases between 2017-2019. Inclusion criteria was an otoneurologically confirmed diagnosis of acute VN. Patient data was compared with data of the German normal population (Robert Koch Institute, "Gesundheit in Deutschland aktuell"). RESULTS: 168 patients (Ø 59.8 years) were included. Compared with the normal German population, the study population was significantly more likely to have preexisting cardiovascular diseases, and the male patients were significantly more likely to have arterial hypertension. No significant differences were measurable between the study population and the normal population for other secondary diseases. Leukocytosis was present in 23% on admission, and 9% of patients reported a history of VZV or HSV-1 disease. DISCUSSION: Etiology and pathogenesis of VN are poorly understood. Inflammatory and vascular causes are discussed. In this study, patients had increased prevalence of cardiovascular disease compared with the normal population, but the study population had a higher average age. Currently, it is unclear what significance nonspecific elevated leukocyte values could have as a possible sign of VN triggered by an infection. Since the number of inpatient cases with VN is rising, prospective studies should be performed to get a better understanding of the pathogenesis of the disease.

Subgroup Analysis of Overall Survival among Smoking and Non-Smoking Elderly Patients with HNSCC.

Smoking is a leading cause of head and neck squamous cell carcinoma (HNSCC). However, non-smokers are also affected by HNSCC, and the prognostic factors applicable to older non-smokers with HNSCC are largely unknown. The aim of this study was to determine predictors of overall survival (OS) in patients both with and without a smoking history aged 70 and over at initial diagnosis. Retrospective data of patients aged ≥70 (initial diagnoses 2004-2018) were examined. Evaluated predictors included tumour stage, biological age, health and therapy. A total of 688 patients (520 smokers, 168 non-smokers) were included with a median age of 74. The 5-year OS was 39.6%. Non-smokers had significantly improved OS compared to smokers (52.0% versus 36.0%, p < 0.001). Disease-free survival (DFS) differed significantly between both groups (hazard ratio = 1.3; 95%CI 1.04-1.626). TNM stage and the recommended therapies (curative versus palliative) were comparable. The proportion of p16-positive oropharyngeal carcinomas was significantly higher in non-smokers (76.7% versus 43.8%, p < 0.001). Smokers were significantly more likely to be men (p < 0.001), drinkers (p < 0.001), and have poorer health status (Karnofsky performance status, KPS, p = 0.023). They were also more likely to have additional tumours (p = 0.012) and lower treatment adherence (p = 0.038). Important predictors of OS identified in both groups, were, among others, alcohol abuse, KPS, Charlson comorbidity index, site of primary tumour, UICC stage and treatment received. Elderly non-smokers are also affected by HNSCC, however, both OS and DFS are increased compared to smokers.

Restoring speech intelligibility for hearing aid users with deep learning.

Almost half a billion people world-wide suffer from disabling hearing loss. While hearing aids can partially compensate for this, a large proportion of users struggle to understand speech in situations with background noise. Here, we present a deep learning-based algorithm that selectively suppresses noise while maintaining speech signals. The algorithm restores speech intelligibility for hearing aid users to the level of control subjects with normal hearing. It consists of a deep network that is trained on a large custom database of noisy speech signals and is further optimized by a neural architecture search, using a novel deep learning-based metric for speech intelligibility. The network achieves state-of-the-art denoising on a range of human-graded assessments, generalizes across different noise categories and-in contrast to classic beamforming approaches-operates on a single microphone. The system runs in real time on a laptop, suggesting that large-scale deployment on hearing aid chips could be achieved within a few years. Deep learning-based denoising therefore holds the potential to improve the quality of life of millions of hearing impaired people soon.

Non-intrusive deep learning-based computational speech metrics with high-accuracy across a wide range of acoustic scenes.

Speech with high sound quality and little noise is central to many of our communication tools, including calls, video conferencing and hearing aids. While human ratings provide the best measure of sound quality, they are costly and time-intensive to gather, thus computational metrics are typically used instead. Here we present a non-intrusive, deep learning-based metric that takes only a sound sample as an input and returns ratings in three categories: overall quality, noise, and sound quality. This metric is available via a web API and is composed of a deep neural network ensemble with 5 networks that use either ResNet-26 architectures with STFT inputs or fully-connected networks with wav2vec features as inputs. The networks are trained and tested on over 1 million crowd-sourced human sound ratings across the three categories. Correlations of our metric with human ratings exceed or match other state-of-the-art metrics on 51 out of 56 benchmark scenes, while not requiring clean speech reference samples as opposed to metrics that are performing well on the other 5 scenes. The benchmark scenes represent a wide variety of acoustic environments and a large selection of post-processing methods that include classical methods (e.g. Wiener-filtering) and newer deep-learning methods.

Effects of the COVID-19 Pandemic on Head and Neck Cancer Stage and Treatment Duration.

Objective To assess the efficacy of oncologic healthcare during the COVID-19 pandemic on patients with head and neck squamous cell carcinoma (SCC) in a tertiary university hospital in Germany. Methods This retrospective, cross-sectional, observational study included 94 patients with newly diagnosed head and neck squamous cell carcinoma during a two-year period. Patients were assigned to two date-dependent groups; referrals before (group A) and during (group B) the COVID-19 pandemic. Time intervals from the symptom(s) onset to diagnosis, diagnosis to treatment, and treatment initiation to completion were recorded. Furthermore, TNM stages and the application of reconstructive surgery with free tissue transfer were determined. Patients' outcomes and characteristics were compared between the two groups. Finally, a comprehensive literature review was carried out to identify similar epidemiological studies. Results The symptom-to-diagnosis interval was longer during the COVID-19 pandemic [median 9.5 (A) versus 15 (B) weeks, p = 0.054]. The intervals from diagnosis to treatment and treatment initiation to end of treatment were approximately the same in both groups [median 3 (A) versus 3.2 (B) weeks, p = 0.264; and 6.9 (A) versus 6.3 (B) weeks, p = 0.136]. The T-and N-stages were not higher during the pandemic [early T-stage (T1+T2) versus advanced T-stage (T3+T4), p = 0.668; and N-negative (N0) versus N-positive status (N1,2,3), p = 0.301]. Patients who presented with distant metastatic disease and those who underwent reconstructive surgery with free tissue transfer were observed more frequently in the lockdown phase [M1 versus M0, p= 0.022; and flap versus no flap, p=0.007]. Conclusion This study suggests the consistent diagnostic and therapeutical performance of the tertiary oncologic healthcare in Berlin, Germany, despite the challenges that patient care units faced during the COVID-19 pandemic.

Detailed seed cone morpho-anatomy of the Prumnopityoid clade: an insight into the origin and evolution of Podocarpaceae seed cones.

BACKGROUND AND AIMS: Seed cone traits are significant for understanding the evolutionary history of conifers. Podocarpaceae has fleshy cones with a distinct morphology compared with other conifers. However, we have a poor understanding of the seed cone morphology of the Prumnopityoid clade and within Podocarpaceae. This study presents detailed seed cone morpho-anatomy and the evolution of fleshy structures traits in the Prumnopityoid clade. METHODS: We investigated the detailed seed cone morpho-anatomy of selected species from the nine genera using the histological method. The evolution of morpho-anatomical traits was assessed using ancestral state reconstruction methods. KEY RESULTS: The Prumnopityoid clade has evolved fleshy seed cones using different functional structures (e.g. aril, epimatium, bracts or receptaculum) and fleshiness is an ancestral trait in the clade. An epimatium is present in all genera except Phyllocladus, but with different structural morphologies (e.g. a fleshy asymmetrical cup-like epimatium or an epimatium that is fused with the integument, forming a fleshy sarcotesta-like seed coat). In all species with fleshy sarcotesta-like seed coats, the endotesta is hard and woody, forming a sclerotesta-like structure and the epimatium and exotesta are fused, forming a fleshy sarcotesta-like structure. CONCLUSIONS: This study highlights that the Prumnopityoid clade has an amazing diversity of structures and complex evolutionary patterns. Fleshiness is an ancestral trait of the clade and has been achieved via diverse evolutionary pathways and structures. This clade has four distinct seed cone types, i.e. drupe-like, receptaculate, arilloid and dacrydioid cones, based on morpho-anatomical structures and traits. The macrofossil record also demonstrates the presence of several structures and traits.

Predictors for Adherence to Treatment Strategies in Elderly HNSCC Patients.

Finding a cure may be less important than ensuring the quality of life in elderly patients with head and neck squamous cell carcinoma (HNSCC). The aim of this study was to determine predictors for adherence. Clinical and pathological data from patients ≥70 years with HNSCC (initial diagnoses 2004-2018) were investigated retrospectively. Evaluated clinical predictors included biological age (Charlson Comorbidity Index; CCI), patient health (Karnofsky Performance Status; KPS) and therapy data. A total of 1125 patients were included. The median age was 75 years, 33.1% reached CCI ≥ 6, and 53.7% reached KPS ≤ 70%. In total, 968 patients were adherent, whereas 157 were nonadherent. Nonadherent patients were significantly more often smokers (p = 0.003), frequent drinkers (p = 0.001), had a worse health status (p ≤ 0.001) and a lower biological age (p = 0.003), an advanced T classification and lymph node involvement or UICC stage (each p ≤ 0.001). Approximately 88.0% of the included patients received a curative treatment recommendation. A total of 6.9% discontinued the therapy, and 7.0% refused the therapy. With the increasing complexity of a recommended therapy, adherence decreased. The 5-year overall survival was significantly higher in adherent patients (45.1% versus 19.2%). In contrast to the chronological patient age, biological age is a significant predictor for adherence. The evaluated predictors for nonadherence need to be verified prospectively.

Subventricular zone involvement is associated with worse outcome in glioma WHO grade 2 depending on molecular markers.

Neural stem cells within the subventricular zone were identified as cells of origin driving growth of high-grade gliomas, and anatomical involvement of the subventricular zone has been associated with an inferior clinical outcome. Whether the association between poor outcome and subventricular zone involvement also applies to glioma of lower grades is unclear. We therefore analysed a retrospective cohort of 182 patients with glioma grade 2 (according to the WHO 2016 classification) including 78 individuals (43%) with subventricular zone involvement. Patients with and without subventricular zone involvement did not differ in regard to demographics, histopathology, and molecular markers. Notably, subventricular zone involvement was a negative prognostic marker for malignant progression and overall survival on uni- and multivariate analysis. When patients were stratified according to the cIMPACT-NOW update 6, subventricular zone involvement was negatively associated with outcome in IDH-wildtype astrocytomas and 1p19q-codeleted oligodendrogliomas but not in IDH-mutant astrocytomas. Collectively, subventricular zone involvement may represent a risk factor for worse outcome in glioma WHO grade 2 depending on the molecular tumor signature. The present data confirm the relevance of molecular glioma classifications as proposed by the cIMPACT-NOW update 6. These findings warrant evaluation in prospective cohorts.