Primary or secondary chronic functional dizziness: does it make a difference?

In 2017, the term \textquotedblpersistent postural-perceptual dizziness\textquotedbl (PPPD) was coined by the Bárány Society, which provided explicit criteria for diagnosis of functional vertigo and dizziness disorders. PPPD can originate secondarily after an organic disorder (s-PPPD) or primarily on its own, in the absence of somatic triggers (p-PPPD). The aim of this database-driven study in 356 patients from a tertiary vertigo center was to describe typical demographic and clinical features in p-PPPD and s-PPPD patients. Patients underwent detailed vestibular testing with neurological and neuro-orthoptic examinations, video-oculography during water caloric stimulation, video head-impulse test, assessment of the subjective visual vertical, and static posturography. All patients answered standardized questionnaires (Dizziness Handicap Inventory, DHI; Vestibular Activities and Participation, VAP; and Euro-Qol-5D-3L). One hundred and ninety-five patients (55%) were categorized as p-PPPD and 162 (45%) as s-PPPD, with female gender slightly predominating (♀:♂ = 56%:44%), particularly in the s-PPPD subgroup (64%). The most common somatic triggers for s-PPPD were benign paroxysmal positional vertigo (27%), and vestibular migraine (24%). Overall, p-PPPD patients were younger than s-PPPD patients (44 vs. 48~years) and showed a bimodal age distribution with an additional early peak in young adults (about 30~years of age) beside a common peak at the age of 50-55. The most sensitive diagnostic tool was posturography, revealing a phobic sway pattern in 50% of cases. s-PPPD patients showed higher handicap and functional impairment in DHI (47 vs. 42) and VAP (9.7 vs. 8.9). There was no difference between both groups in EQ-5D-3L. In p-PPPD, anxiety (20% vs. 10%) and depressive disorders (25% vs. 9%) were more frequent. This retrospective study in a large cohort showed relevant differences between p- and s-PPPD patients in terms of demographic and clinical features, thereby underlining the need for careful syndrome subdivision for further prospective studies

Episodic ataxias in children and adolescents: Clinical findings and suggested diagnostic criteria

Background: The main clinical presentation of episodic ataxias (EAs) consists of vertigo and dizziness attacks lasting for minutes to hours with widely varying accompanying symptoms. The differentiation of EA and episodic vertigo/dizziness syndromes in childhood and adolescence such as vestibular migraine (VM) and recurrent vertigo of childhood (RVC) can be challenging. Furthermore, only few prospective studies of children/adolescents with EA are available. Objective: This study aims to characterize clinical and instrument-based findings in EA patients under 18 years of age, to delineate the clinical and therapeutic course in EA, and to present potentially new genetic mutations. Furthermore, the study aims to differentiate distinct characteristics between EA, VM, and RVC patients. Methods: We prospectively collected clinical and instrument-based data of patients younger than 18 years, who presented at the German Center for Vertigo and Balance Disorders (DSGZ) at the LMU University Hospital in Munich with EA, VM, or RVC between January 2016 and December 2021. All patients underwent a comprehensive evaluation of neurological, ocular-motor, vestibular and cochlear function, including video-oculography with caloric testing, video head impulse test, vestibular evoked myogenic potentials, posturography, and gait analysis. Results: Ten patients with EA, 15 with VM, and 15 with RVC were included. In EA the main symptoms were vertigo/dizziness attacks lasting between 5 min and 12 h. Common accompanying symptoms included walking difficulties, paleness, and speech difficulties. Six EA patients had a previously unknown gene mutation. In the interictal interval all EA patients showed distinct ocular-motor deficits. Significant differences between EA, VM, and RVC were found for accompanying symptoms such as speech disturbances and paleness, and for the trigger factor “physical activity”. Furthermore, in the interictal interval significant group differences were observed for different pathological nystagmus types, a saccadic smooth pursuit, and disturbed fixation suppression. Conclusion: By combining clinical and ocular-motor characteristics we propose diagnostic criteria that can help to diagnose EA among children/adolescents and identify patients with EA even without distinct genetic findings. Nevertheless, broad genetic testing (e.g., next generation sequencing) in patients fulfilling the diagnostic criteria should be conducted to identify even rare or unknown genetic mutations for EA

Percutaneous CT fluoroscopy-guided core biopsy of pancreatic lesions: technical and clinical outcome of 104 procedures during a 10-year period

Background: In unclear pancreatic lesions, a tissue sample can confirm or exclude the suspected diagnosis and help to provide an optimal treatment strategy to each patient. To date only one small study reported on the outcome of computed tomography (CT) fluoroscopy-guided biopsies of the pancreas. Purpose: To evaluate technical success and diagnostic rate of all CT fluoroscopy-guided core biopsies of the pancreas performed in a single university center during a 10-year period. Material and Methods: In this retrospective study we included all patients who underwent a CT fluoroscopy-guided biopsy of a pancreatic mass at our comprehensive cancer center between 2005 and 2014. All interventions were performed under local anesthesia on a 16-row or 128-row CT scanner. Technical success and diagnostic rates as well as complications and effective patient radiation dose were analyzed. Results: One hundred and one patients (54 women;mean age, 63.912.6 years) underwent a total of 104 CT fluoroscopy-guided biopsies of the pancreas. Ninety-eight of 104 interventions (94.2%) could be performed with technical success and at least one tissue sample could be obtained. In 88 of these 98 samples, a definitive pathological diagnosis, consistent with clinical success could be achieved (89.8%). Overall 19 minor and three major complications occurred during the intra- or 30-day post-interventional period and all other interventions could be performed without complications;there was no death attributable to the intervention. Conclusion: CT fluoroscopy-guided biopsy of pancreatic lesions is an effective procedure characterized by a low major complication and a high diagnostic rate

CT fluoroscopy-guided percutaneous osteoplasty with or without radiofrequency ablation in the treatment of painful extraspinal and spinal bone metastases: technical outcome and complications in 29 patients

PURPOSE:We aimed to assess the safety and technical outcome of computed tomography (CT) fluoroscopy-guided osteoplasty with or without prior percutaneous radiofrequency ablation (RFA) in patients with painful osteolyses.METHODS:We performed a retrospective analysis of 29 patients with painful extraspinal and spinal osteo- lyses (16 women, 13 men; 63.1±14.4 years) who underwent CT fluoroscopy-guided osteoplasty (10-20 mAs tube current) with or without RFA (26 and 14 lesions, respectively), in 33 consecutive procedures from 2002 to 2016. Technical success was defined as at least one complete RFA cycle and subsequent polymethyl metacrylate (PMMA) bone cement injection covering ≥75% of longest diameter of extraspinal osteolysis on axial plane or of distance between vertebral endplates. Procedure-related complications within 30 days and dose-length-product (DLP) were also evaluated.RESULTS:Osteolyses were located in the pelvis (acetabulum, n=10; iliac bone, n=4), spine (thoracic, n=6; lumbar, n=5; sacral, n=8), long bones (femur, n=3; tibia, n=1), sternum (n=2) and glenoid (n=1). Mean size of the treated osteolysis was 4.0±1.2 cm (range, 1.9–6.9 cm). Of 40 osteolyses, 31 (77.5%) abutted neighboring risk structures (spinal canal or neuroforamen, n=18; neighboring joint, n=11; other, n=8). Mean number of RFA electrode positions and complete ablation cycles was 1.5±0.9 and 2.1±1.7, respectively. Mean PMMA filling volume was 7.7±5.7 mL (range, 2–30 mL). Small asymptomatic PMMA leakages were observed in 15 lesions (37.5%). Mean total DLP was 850±653 mGy*cm. Six minor complications were observed, without any major complications.CONCLUSION:CT fluoroscopy-guided percutaneous osteoplasty with or without concomitant RFA for the treatment of painful extraspinal and spinal osteolyses can be performed with a low complication rate and high technical success

BlenderProc2: A Procedural Pipeline for Photorealistic Rendering

BlenderProc2 is a procedural pipeline that can render realistic images for the training of neural networks. Our pipeline can be employed in various use cases, including segmentation, depth, normal and pose estimation, and many others. A key feature of our Blender extension is the simple-to-use python API, designed to be easily extendable. Furthermore, many public datasets, such as 3D FRONT (Fu et al., 2021) or Shapenet (Chang et al., 2015), are already supported, making it easier to clutter synthetic scenes with additional objects

Immunosuppressive niche engineering at the onset of human colorectal cancer

The evolutionary dynamics of tumor initiation remain undetermined, and the interplay between neoplastic cells and the immune system is hypothesized to be critical in transformation. Colorectal cancer (CRC) presents a unique opportunity to study the transition to malignancy as pre-cancers (adenomas) and early-stage cancers are frequently resected. Here, we examine tumor-immune eco-evolutionary dynamics from pre-cancer to carcinoma using a computational model, ecological analysis of digital pathology data, and neoantigen prediction in 62 patient samples. Modeling predicted recruitment of immunosuppressive cells would be the most common driver of transformation. As predicted, ecological analysis reveals that progressed adenomas co-localized with immunosuppressive cells and cytokines, while benign adenomas co-localized with a mixed immune response. Carcinomas converge to a common immune “cold” ecology, relaxing selection against immunogenicity and high neoantigen burdens, with little evidence for PD-L1 overexpression driving tumor initiation. These findings suggest re-engineering the immunosuppressive niche may prove an effective immunotherapy in CRC

Combining targeted and systematic prostate biopsy improves prostate cancer detection and correlation with the whole mount histopathology in biopsy naïve and previous negative biopsy patients

OBJECTIVE: Guidelines for previous negative biopsy (PNB) cohorts with a suspicion of prostate cancer (PCa) after positive multiparametric (mp) magnetic-resonance-imaging (MRI) often favour the fusion-guided targeted prostate-biopsy (TB) only approach for Prostate Imaging-Reporting and Data System (PI-RADS) ≥3 lesions. However, recommendations lack direct biopsy performance comparison within biopsy naïve (BN) vs. PNB patients and its prognostication of the whole mount pathology report (WMPR), respectively. We suppose, that the combination of TB and concomitant TRUS-systematic biopsy (SB) improves the PCa detection rate of PI-RADS 2, 3, 4 or 5 lesions and the International Society of Urological Pathology (ISUP)-grade predictability of the WMPR in BN- and PNB patients. METHODS: Patients with suspicious mpMRI, elevated prostate-specific-antigen and/or abnormal digital rectal examination were included. All PI-RADS reports were intramurally reviewed for biopsy planning. We compared the PI-RADS score substratified TB, SB or combined approach (TB/SB) associated BN- and PNB-PCa detection rate. Furthermore, we assessed the ISUP-grade variability between biopsy cores and the WMPR. RESULTS: According to BN (n = 499) vs. PNB (n = 314) patients, clinically significant (cs) PCa was detected more frequently by the TB/SB approach (62 vs. 43%) than with the TB (54 vs. 34%) or SB (57 vs. 34%) (all p < 0.0001) alone. Furthermore, we observed that the TB/SB strategy detects a significantly higher number of csPCa within PI-RADS 3, 4 or 5 reports, both in BN and PNB men. In contrast, applied biopsy techniques were equally effective to detect csPCa within PI-RADS 2 lesions. In case of csPCa diagnosis the TB approach was more often false-negative in PNB patients (BN 11% vs. PNB 19%; p = 0.02). The TB/SB technique showed in general significantly less upgrading, whereas a higher agreement was only observed for the total and BN patient cohort. CONCLUSION: Despite csPCa is more frequently found in BN patients, the TB/SB method always detected a significantly higher number of csPCa within PI-RADS 3, 4 or 5 reports of our BN and PNB group. The TB/SB strategy predicts the ISUP-grade best in the total and BN cohort and in general shows the lowest upgrading rates, emphasizing its value not only in BN but also PNB patients

On simulated annealing phase transitions in phylogeny reconstruction

Phylogeny reconstruction with global criteria is NP-complete or NP-hard, hence in general requires a heuristic search. We investigate the powerful, physically inspired, general-purpose heuristic simulated annealing, applied to phylogeny reconstruction. Simulated annealing mimics the physical process of annealing, where a liquid is gently cooled to form a crystal. During the search, periods of elevated specific heat occur, analogous to physical phase transitions. These simulated annealing phase transitions play a crucial role in the outcome of the search. Nevertheless, they have received comparably little attention, for phylogeny or other optimisation problems. We analyse simulated annealing phase transitions during searches for the optimal phylogenetic tree for 34 real-world multiple alignments. In the same way in which melting temperatures differ between materials, we observe distinct specific heat profiles for each input file. We propose this reflects differences in the search landscape and can serve as a measure for problem difficulty and for suitability of the algorithm’s parameters. We discuss application in algorithmic optimisation and as a diagnostic to assess parameterisation before computationally costly, large phylogeny reconstructions are launched. Whilst the focus here lies on phylogeny reconstruction under maximum parsimony, it is plausible that our results are more widely applicable to optimisation procedures in science and industry

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe