Prostate-specific membrane antigen-radioguided surgery salvage lymph node dissection: experience with fifty oligorecurrent prostate cancer patients.

PURPOSE: The higher detection efficacy of PSMA PET for oligometastatic recurrence of prostate cancer has promoted new loco-regional treatment options. PSMA-targeted radioguided surgery (PSMA-RGS) was introduced to facilitate salvage surgery of small tumor deposits. The objectives of this retrospective analysis are to describe an independent single-center consecutive cohort of patients undergoing PSMA-RGS and to evaluate its clinical and oncological outcomes. METHOD: Between 2018 and 2022, 53 patients were treated with PSMA-RGS and 50 patients were available for final analyses. All patients were initially treated with radical prostatectomy (RP) and presented with biochemical recurrence (BCR) with at least one positive lesion on PSMA-PET imaging. After preparation of 99mTc-PSMA-I&S and intravenous injection, surgery was performed by using a gamma-probe intraoperatively. RESULTS: Median age was 70 years (IQR 65-73) and the median PSA at salvage surgery was 1.2 ng/mL (IQR 0.6-3.0). In all patients pathologically positive lesions could be removed during PSMA-RGS. 29 (58%) patients had one pathologically positive lesion, 14 (28%) had two and 7 (14%) had three or more, respectively. The overall complication rate was 26% with 4 (8%), 1 (2%), and 8 (16%) having Clavien-Dindo (CD) type I, II, and IIIb complications, respectively. During the follow-up period 31 (62%) patients experienced BCR and 29 (58%) received further therapy. CONCLUSIONS: PSMA-RGS is a promising treatment option to enhance salvage surgery in early biochemical recurrence. However, only 42% of the patients treated with PSMA RGS remain without a biochemical recurrence. Further research is mandatory to identify patients, who profit from PSMA-RGS.

Clinical implementation of minimally invasive esophagectomy.

BACKGROUND: Minimally invasive surgery is becoming the method of choice for the resection of esophageal cancer worldwide. METHODS: Retrospective analysis of prospectively collected clinical data in a tertiary care center with a detailed description of the course of the program. RESULTS: A total of 136 transthoracic esophageal resections were performed between 2010 and 2023. The study group included 116 operations, 69 of which were fully minimally invasive and 47 hybrid. 80.0% of the study group underwent surgery using a multimodality approach. The median operation time was 431 min (± 103). The R0 resection rate was 100%. Forty-two patients (36.2%) had no postoperative complications. The postoperative Clavien-Dindo > IIIb morbidity was 27%. The postoperative 90-d mortality rate was 1.7%. The average number of lymph nodes removed in the last quarter of cancer patients was 31. The anastomotic insufficiency rate for reoperation was 4% (Ivor-Lewis 4.2%, McKeown 5%). CONCLUSIONS: With extensive expertise in high-end minimally invasive abdominal and thoracic surgery, implementation of a minimally invasive esophageal resection program with a clinical and oncologic outcome within generally accepted limits is feasible.

Long-term occlusal tooth wear at the onset of permanent dentition.

OBJECTIVES: This study quantified the long-term occlusal wear in the natural posterior teeth and the associations per tooth type within the dentition. METHODS: The sample included 70 orthodontically treated subjects (52 females and 18 males; median age, 14.3 years), followed for a 12.7-year period. They were consecutively selected with no tooth wear-related criteria. Post-treatment (T1) and follow-up dental casts (T2) were scanned and superimposed through three-dimensional methods. Occlusal wear volume of posterior teeth and tooth wear patterns were investigated through non-parametric statistics and analysis of covariance. RESULTS: There were no significant differences between contralateral teeth. The average occlusal wear per posterior tooth was 2.3 mm3, with 65.2% of teeth showing values greater than 1 mm3. Males, mandibular teeth, and first molars exhibited slightly greater wear levels than females (median, 2.57 and 2.21 mm3, respectively; p = 0.005), maxillary teeth, and first or second premolars, respectively. In all first premolars and in the mandibular second premolars, the buccal cusps were primarily affected with no other distinct patterns. There were weak to moderate correlations between tooth types, apart from certain strong correlations detected in males. CONCLUSIONS: Posterior tooth wear was highly prevalent after a 13-year period starting at the onset of permanent dentition. The detected patterns are in accordance with the concept of canine guidance occlusion that is transforming into group synergy through function. CLINICAL RELEVANCE: The widespread tooth wear occurrence and the high intra- and inter-individual variability underline the need for individual patient monitoring to identify high-risk patients at early stages.

Experimental investigation of skin toxicity after immune checkpoint inhibition in combination with radiation therapy.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy. However, structured knowledge to mitigate a patient's specific risk of developing adverse events are limited. Nevertheless, there is an exponential growth of clinical studies combining conventional therapies such as radiation therapy (RT) with ICIs. Cutaneous reactions are among the most common adverse events after monotherapy with either ICIs or RT. So far, little is known about interindividual differences for the risk of developing severe tissue toxicity after the combination of RT with ICIs, and the underlying biological mechanisms are ill defined. We used experimental models of RT-induced skin injury to analyze skin toxicity after simultaneous application of ICIs. We compared different RT regimens such as fractionated or stereotactic RT with varying dose intensity. Strikingly, we found that simultaneous application of RT and ICIs did not significantly aggravate acute skin injury in two different mouse strains. Detailed examination of long-term tissue damage of the skin revealed similar signs of epidermal hyperplasia, dermal fibrosis, and adnexal atrophy. In summary, we here present the first experimental study demonstrating the excellent safety profiles of concurrent treatment with RT and ICIs. These findings will help to interpret the development of adverse events of the skin after radioimmunotherapy and guide the design of new clinical trials and clinical decision-making in individual cases. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Advances in spiral fMRI: A high-resolution study with single-shot acquisition.

Spiral fMRI has been put forward as a viable alternative to rectilinear echo-planar imaging, in particular due to its enhanced average k-space speed and thus high acquisition efficiency. This renders spirals attractive for contemporary fMRI applications that require high spatiotemporal resolution, such as laminar or columnar fMRI. However, in practice, spiral fMRI is typically hampered by its reduced robustness and ensuing blurring artifacts, which arise from imperfections in both static and dynamic magnetic fields. Recently, these limitations have been overcome by the concerted application of an expanded signal model that accounts for such field imperfections, and its inversion by iterative image reconstruction. In the challenging ultra-high field environment of 7 Tesla, where field inhomogeneity effects are aggravated, both multi-shot and single-shot 2D spiral imaging at sub-millimeter resolution was demonstrated with high depiction quality and anatomical congruency. In this work, we further these advances towards a time series application of spiral readouts, namely, single-shot spiral BOLD fMRI at 0.8 mm in-plane resolution. We demonstrate that high-resolution spiral fMRI at 7 T is not only feasible, but delivers both excellent image quality, BOLD sensitivity, and spatial specificity of the activation maps, with little artifactual blurring. Furthermore, we show the versatility of the approach with a combined in/out spiral readout at a more typical resolution (1.5 mm), where the high acquisition efficiency allows to acquire two images per shot for improved sensitivity by echo combination.

X-ray Dark-Field CT for Early Detection of Radiation-induced Lung Injury in a Murine Model.

Online supplemental material is available for this article.

Formation Mechanism of a Nano-Ring of Bismuth Cations and Mono-Lacunary Keggin-Type Phosphomolybdate.

A new hetero-bimetallic polyoxometalate (POM) nano-ring was synthesized in a one-pot procedure. The structure consists of tetrameric units containing four bismuth-substituted monolacunary Keggin anions including distorted [BiO8 ] cubes. The nano-ring is formed via self-assembly from metal precursors in aqueous acidic medium. The compound (NH4 )16 [(BiPMo11 O39 )4 ] ⋅ 22 H2 O; (P4 Bi4 Mo44 ) was characterized by single-crystal X-ray diffraction, extended X-ray absorption fine structure spectroscopy (EXAFS), Raman spectroscopy, matrix-assisted laser desorption/ionisation-time of flight mass spectrometry (MALDI-TOF), and thermogravimetry/differential scanning calorimetry mass spectrometry (TG-DSC-MS). The formation of the nano-ring in solution was studied by time-resolved in situ small- and wide-angle X-ray scattering (SAXS/WAXS) and in situ EXAFS measurements at the Mo-K and the Bi-L3 edge indicating a two-step process consisting of condensation of Mo-anions and formation of Bi-Mo-units followed by a rapid self-assembly to yield the final tetrameric ring structure.

Driving ability after right-sided inguinal hernia surgery.

PURPOSE: To investigate driving ability (brake reaction time, BRT) after right-sided hernia repair. It was assumed that postoperatively BRT would be impaired as compared to the preoperative reference and healthy controls. METHODS: BRT was prospectively collected from 30 patients undergoing hernia repair [Lichtenstein or total extraperitoneal endoscopic procedure (TEP)]. BRT was measured with a driving simulator preoperatively and on postoperative days 2 and 14. After receiving a visual stimulus, the patients had to apply the brake pedal with 160 N. The average of ten runs was used as the patient's BRT value. RESULTS: Thirty patients completed all measurements. In the Lichtenstein group, BRT was significantly impaired as compared to the patient's preoperative values (p = 0.021). Two weeks after surgery BRT had returned to the preoperative level (p = 0.859). BRT in the Lichtenstein group was also significantly impaired 2 days postoperatively as compared to the BRT of 60 healthy controls (p = 0.001). In the TEP group, no impaired BRT was detected. CONCLUSIONS: Based on our finding of significantly impaired BRT in patients following right-sided Lichtenstein hernia repair, it seems wise to recommend that such patients refrain from driving for 2 weeks after surgery. No such impairment was found in patients following TEP surgery. Consequently, it is deemed safe for them to resume driving 2 days after the procedure.

Local inhibition of rRNA transcription without nucleolar segregation after targeted ion irradiation of the nucleolus.

Nucleoli have attracted interest for their role as cellular stress sensors and as potential targets for cancer treatment. The effect of DNA double-strand breaks (DSBs) in nucleoli on rRNA transcription and nucleolar organisation appears to depend on the agent used to introduce DSBs, DSB frequency and the presence (or not) of DSBs outside the nucleoli. To address the controversy, we targeted nucleoli with carbon ions at the ion microbeam SNAKE. Localized ion irradiation with 1-100 carbon ions per point (about 0.3-30 Gy per nucleus) did not lead to overall reduced ribonucleotide incorporation in the targeted nucleolus or other nucleoli of the same cell. However, both 5-ethynyluridine incorporation and Parp1 protein levels were locally decreased at the damaged nucleolar chromatin regions marked by γH2AX, suggesting localized inhibition of rRNA transcription. This locally restricted transcriptional inhibition was not accompanied by nucleolar segregation, a structural reorganisation observed after inhibition of rRNA transcription by treatment with actinomycin D or UV irradiation. The presented data indicate that even multiple complex DSBs do not lead to a pan-nucleolar response if they affect only a subnucleolar region.

On the signal-to-noise ratio benefit of spiral acquisition in diffusion MRI.

PURPOSE: Spiral readouts combine several favorable properties that promise superior net sensitivity for diffusion imaging. The purpose of this study is to verify the signal-to-noise ratio (SNR) benefit of spiral acquisition in comparison with current echo-planar imaging (EPI) schemes. METHODS: Diffusion-weighted in vivo brain data from three subjects were acquired with a single-shot spiral sequence and several variants of single-shot EPI, including full-Fourier and partial-Fourier readouts as well as different diffusion-encoding schemes. Image reconstruction was based on an expanded signal model including field dynamics obtained by concurrent field monitoring. The effective resolution of each sequence was matched to that of full-Fourier EPI with 1 mm nominal resolution. SNR maps were generated by determining the noise statistics of the raw data and analyzing the propagation of equivalent synthetic noise through image reconstruction. Using the same approach, maps of noise amplification due to parallel imaging (g-factor) were calculated for different acceleration factors. RESULTS: Relative to full-Fourier EPI at b = 0 s/mm2 , spiral acquisition yielded SNR gains of 42-88% and 40-89% in white and gray matter, respectively, depending on the diffusion-encoding scheme. Relative to partial-Fourier EPI, the gains were 36-44% and 34-42%. Spiral g-factor maps exhibited less spatial variation and lower maxima than their EPI counterparts. CONCLUSION: Spiral readouts achieve significant SNR gains in the order of 40-80% over EPI in diffusion imaging at 3T. Combining systematic effects of shorter echo time, readout efficiency, and favorable g-factor behavior, similar benefits are expected across clinical and neurosciences uses of diffusion imaging.

Copeptin, pro-atrial natriuretic peptide and pro-adrenomedullin as markers of hypoxic stress in patients with obstructive sleep apnea-a prospective intervention study.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) might lead to oxidative stress, inflammation and elevated circulating copeptin, proANP and proADM levels. We aimed to evaluate whether the levels of these prohormones are higher in patients with OSA and whether they might change under continuous positive airway pressure (CPAP) therapy, serving as potential proxies for the diagnosis and therapy-response in OSA. METHODS: A total of 310 patients with suspicion of OSA were recruited. Screening for OSA was performed using overnight pulse oximetry followed by polygraphy and a venous puncture in the morning. All patients diagnosed with OSA underwent CPAP adaptation. A venous puncture was conducted in the night before CPAP and in the following morning. At 1 and 6 months of treatment, polygraphy was performed, followed by a venous puncture in the morning. In the acquired blood, copeptin, proANP and proADM levels were measured. RESULTS: We analyzed 232 patients with OSA and 30 patients without OSA. Our results indicated that only copeptin levels differed significantly among patients with and without OSA at baseline. In OSA patients, the levels of proADM significantly changed after 1 and 6 months on CPAP therapy, when compared to baseline (p < 0.001 and p = 0.020). Additionally, proANP levels significantly decreased after 12 h on CPAP therapy, as compared to baseline levels (p < 0.001). CONCLUSIONS: Copeptin is significantly associated with the presence of OSA. ProANP levels might serve as a potential proxy for the acute response to non-invasive ventilation (12 h), while proADM reflects the long-term response (1 and 6 months).

Early detection of radiation-induced lung damage with X-ray dark-field radiography in mice.

OBJECTIVE: Assessing the advantage of x-ray dark-field contrast over x-ray transmission contrast in radiography for the detection of developing radiation-induced lung damage in mice. METHODS: Two groups of female C57BL/6 mice (irradiated and control) were imaged obtaining both contrasts monthly for 28 weeks post irradiation. Six mice received 20 Gy of irradiation to the entire right lung sparing the left lung. The control group of six mice was not irradiated. A total of 88 radiographs of both contrasts were evaluated for both groups based on average values for two regions of interest, covering (irradiated) right lung and healthy left lung. The ratio of these average values, R, was distinguished between healthy and damaged lungs for both contrasts. The time-point when deviations of R from healthy lung exceeded 3σ was determined and compared among contrasts. The Wilcoxon-Mann-Whitney test was used to test against the null hypothesis that there is no difference between both groups. A selection of 32 radiographs was assessed by radiologists. Sensitivity and specificity were determined in order to compare the diagnostic potential of both contrasts. Inter-reader and intra-reader accuracy were rated with Cohen's kappa. RESULTS: Radiation-induced morphological changes of lung tissue caused deviations from the control group that were measured on average 10 weeks earlier with x-ray dark-field contrast than with x-ray transmission contrast. Sensitivity, specificity, and accuracy doubled using dark-field radiography. CONCLUSION: X-ray dark-field radiography detects morphological changes of lung tissue associated with radiation-induced damage earlier than transmission radiography in a pre-clinical mouse model. KEY POINTS: • Significant deviations from healthy lung due to irradiation were measured after 16 weeks with x-ray dark-field radiography (p = 0.004). • Significant deviations occur on average 10 weeks earlier for x-ray dark-field radiography in comparison to x-ray transmission radiography. • Sensitivity and specificity doubled when using x-ray dark-field radiography instead of x-ray transmission radiography.

Lomeguatrib Increases the Radiosensitivity of MGMT Unmethylated Human Glioblastoma Multiforme Cell Lines.

BACKGROUND: Treatment resistance of glioblastoma multiforme to chemo- and radiotherapy remains a challenge yet to overcome. In particular, the O6-methylguanine-DNA-methyltransferase (MGMT) promoter unmethylated patients have only little benefit from chemotherapy treatment using temozolomide since MGMT counteracts its therapeutic efficacy. Therefore, new treatment options in radiotherapy need to be developed to inhibit MGMT and increase radiotherapy response. METHODS: Lomeguatrib, a highly specific MGMT inhibitor, was used to inactivate MGMT protein in vitro. Radiosensitivity of established human glioblastoma multiforme cell lines in combination with lomeguatrib was investigated using the clonogenic survival assay. Inhibition of MGMT was analyzed using Western Blot. Cell cycle distribution and apoptosis were investigated to determine the effects of lomeguatrib alone as well as in combination with ionizing radiation. RESULTS: Lomeguatrib significantly decreased MGMT protein and reduced radiation-induced G2/M arrest. A radiosensitizing effect of lomeguatrib was observed when administered at 1 µM and increased radioresistance at 20 µM. CONCLUSION: Low concentrations of lomeguatrib elicit radiosensitization, while high concentrations mediate a radioprotective effect.

[Integrative and complementary primary care medicine: new evidence in 2020]. / Médecine complémentaire intégrative : nouveautés utiles en médecine de premier recours.

Integrative medicine proposes a coordinated approach to conventional medicine and complementary treatments. This approach is of particular interest in the field of prevention and in comprehensive primary care. This article presents some key studies published in 2020, which highlight the potential benefits of an integrative approach in primary care medicine.

La médecine intégrative permet de coordonner médecine conventionnelle et traitements complémentaires. Cette approche est particulièrement intéressante dans le domaine de la prévention et dans la prise en charge globale en médecine de premier recours. Cet article présente quelques études clés, publiées en 2020, qui mettent en lumière les bénéfices potentiels d'une approche intégrative en médecine de premier recours.

Motion detection with NMR markers using real-time field tracking in the laboratory frame.

PURPOSE: To enhance the utility of motion detection with nuclear magnetic resonance (NMR) markers by removing the need for sequence-dependent calibration. METHODS: Two sets of NMR markers are used for simultaneous observation of magnetic field dynamics during imaging procedures. A set of stationary markers at known positions in the laboratory frame serves to determine the field evolution in that frame. Concurrent recording from a set of head-mounted markers then permits calculating their lab-frame positions and derived rigid-body motion parameters. The precision and accuracy of this approach are evaluated relative to current calibration-based solutions. Use for prospective motion correction is then demonstrated in high-resolution imaging of long scan duration. RESULTS: Motion detection with real-time field tracking overcomes the need for explicit calibration without compromising precision, which is assessed at 10 to 30 µm. Relative to full conventional calibration, it is found to offer superior robustness against thermal drift. Relative to more economical modes of calibration, it achieves substantially higher accuracy. Prospective motion correction based on real-time field tracking resulted in consistently high image quality even when head motion exceeded the image resolution by one order of magnitude. CONCLUSION: Real-time field tracking enables motion detection with NMR markers without calibration overhead and thus overcomes a key obstacle toward routine use. In addition, it renders this mode of motion tracking more robust against system imperfections.

A transmit-receive array for brain imaging with a high-performance gradient insert.

PURPOSE: The aim of this work was to provide parallel imaging capability for the human head in a gradient insert of 33-cm inner diameter within the related constraints of space, encoding ambiguity, and eddy current immunity. METHODS: Eddy current behavior of the 8-channel transmit-receive array coil was investigated via heating and field deviation measurements. RF performance was evaluated using S-parameters, noise statistics, B1 maps, and g-factor maps. In vivo images of a human head and knee were acquired with Cartesian readout and TE below 0.45 ms. RESULTS: Under intense gradient use, the shield was heated up to 55°C and other coil structures to 40°C. After standard preemphasis calibration, eddy current-related field distortions caused by the developed RF coil were smaller than for a commercial receive-only coil. In the ambiguous regions of the gradient, B1+ is 20 dB lower than in the center of the FOV. Coupling between elements is below -15 dB, and noise correlation is less than 0.31 when the coil is loaded with a head. Power efficiency was 0.52 ± 0.02 µT/√W, and the SD of the flip angle was below 10% in central slices of the brain. 2D, up to fourfold acceleration causes less than 30% noise amplification. The RF coil can be used during full gradient performance. CONCLUSION: Based on the described features, the presented coil enables parallel imaging in the high-performance gradient insert.

A proof of principle experiment for microbeam radiation therapy at the Munich compact light source.

Microbeam radiation therapy (MRT), a preclinical form of spatially fractionated radiotherapy, uses an array of microbeams of hard synchrotron X-ray radiation. Recently, compact synchrotron X-ray sources got more attention as they provide essential prerequisites for the translation of MRT into clinics while overcoming the limited access to synchrotron facilities. At the Munich compact light source (MuCLS), one of these novel compact X-ray facilities, a proof of principle experiment was conducted applying MRT to a xenograft tumor mouse model. First, subcutaneous tumors derived from the established squamous carcinoma cell line FaDu were irradiated at a conventional X-ray tube using broadbeam geometry to determine a suitable dose range for the tumor growth delay. For irradiations at the MuCLS, FaDu tumors were irradiated with broadbeam and microbeam irradiation at integral doses of either 3 Gy or 5 Gy and tumor growth delay was measured. Microbeams had a width of 50 µm and a center-to-center distance of 350 µm with peak doses of either 21 Gy or 35 Gy. A dose rate of up to 5 Gy/min was delivered to the tumor. Both doses and modalities delayed the tumor growth compared to a sham-irradiated tumor. The irradiated area and microbeam pattern were verified by staining of the DNA double-strand break marker γH2AX. This study demonstrates for the first time that MRT can be successfully performed in vivo at compact inverse Compton sources.

A Mechanistic Perspective on Plastically Flexible Coordination Polymers.

Mechanical flexibility in single crystals of covalently bound materials is a fascinating and poorly understood phenomenon. We present here the first example of a plastically flexible one-dimensional (1D) coordination polymer. The compound [Zn(µ-Cl)2 (3,5-dichloropyridine)2 ]n is flexible over two crystallographic faces. Remarkably, the single crystal remains intact when bent to 180°. A combination of microscopy, diffraction, and spectroscopic studies have been used to probe the structural response of the crystal lattice to mechanical bending. Deformation of the covalent polymer chains does not appear to be responsible for the observed macroscopic bending. Instead, our results suggest that mechanical bending occurs by displacement of the coordination polymer chains. Based on experimental and theoretical evidence, we propose a new model for mechanical flexibility in 1D coordination polymers. Moreover, our calculations propose a cause of the different mechanical properties of this compound and a structurally similar elastic material.

Systematic review of how Play Streets impact opportunities for active play, physical activity, neighborhoods, and communities.

BACKGROUND: Active play and physical activity are important for preventing childhood obesity, building healthy bones and muscles, reducing anxiety and stress, and increasing self-esteem. Unfortunately, safe and accessible play places are often lacking in under-resourced communities. Play Streets (temporary closure of streets) are an understudied intervention that provide safe places for children, adolescents, and their families to actively play. This systematic review examines how Play Streets impact opportunities for children and adolescents to engage in safe active play and physical activity, and for communities and neighborhoods. Methods for evaluating Play Streets were also examined. METHODS: A systematic literature review was conducted in Academic Search Complete, CINHAL, PsycINFO, PubMED, Web of Science, and Google Scholar. Peer-reviewed intervention studies published worldwide were included if they were published in English, through December 2017 and documented free-to-access Play Streets or other temporary spaces that incorporated a designated area for children and/or adolescents to engage in active play. Systematic data extraction documented sample, implementation, and measurement characteristics and outcomes. RESULTS: Of 180 reviewed abstracts, 6 studies met inclusion criteria. Studies were conducted in five different countries (n = 2 in U.S.), using mostly cross-sectional study designs (n = 4). Physical activity outcomes were measured in half of the studies; one used observational and self-report measures, and two used device-based and self-report measures. In general, Play Streets provided safe places for child play, increased sense of community, and when measured, data suggest increased physical activity overall and during Play Streets. CONCLUSIONS: Play Streets can create safe places for children to actively play, with promise of increasing physical activity and strengthening community. Given the popularity of Play Streets and the potential impact for active play, physical activity, and community level benefits, more rigorous evaluations and systematic reporting of Play Streets' evaluations are needed.