Imaging intact human organs from the organ to the cellular scale in three dimensions is a goal of biomedical imaging. To meet this challenge, we developed hierarchical phase-contrast tomography ...(HiP-CT), an X-ray phase propagation technique using the European Synchrotron Radiation Facility (ESRF)'s Extremely Brilliant Source (EBS). The spatial coherence of the ESRF-EBS combined with our beamline equipment, sample preparation and scanning developments enabled us to perform non-destructive, three-dimensional (3D) scans with hierarchically increasing resolution at any location in whole human organs. We applied HiP-CT to image five intact human organ types: brain, lung, heart, kidney and spleen. HiP-CT provided a structural overview of each whole organ followed by multiple higher-resolution volumes of interest, capturing organotypic functional units and certain individual specialized cells within intact human organs. We demonstrate the potential applications of HiP-CT through quantification and morphometry of glomeruli in an intact human kidney and identification of regional changes in the tissue architecture in a lung from a deceased donor with coronavirus disease 2019 (COVID-19).
Introduction
Obturator nerve entrapment or idiopathic obturator neuralgia is an unfamiliar pathology for many physicians which can lead to diagnostic errancy. This study aims to identify the ...potential compression areas of the obturator nerve to improve therapeutic management.
Material and methods
18 anatomical dissections of lower limbs from 9 anatomical cadavers were performed. Endopelvic and exopelvic surgical approaches were utilized to study the anatomical variations of the nerve and to identify areas of entrapment.
Results
On 7 limbs, the posterior branch of the obturator nerve passed through the external obturator muscle. A fascia between the adductor brevis and longus muscles was present in 9 of the 18 limbs. The anterior branch of the obturator nerve was highly adherent to the fascia in 6 cases. In 3 limbs, the medial femoral circumflex artery was in close connection with the posterior branch of the nerve.
Conclusion
Idiopathic obturator neuropathy remains a difficult diagnosis. Our cadaveric study did not allow us to formally identify one or more potential anatomical entrapment zones. However, it allowed the identification of zones at risk. A clinical study with staged analgesic blocks would be necessary to identify an anatomical area of compression and would allow targeted surgical neurolysis.
Imaging across different scales is essential for understanding healthy organ morphology and pathophysiological changes. The macro- and microscale three-dimensional morphology of large samples, ...including intact human organs, is possible with X-ray microtomography (using laboratory or synchrotron sources). Preparation of large samples for high-resolution imaging, however, is challenging due to limitations such as sample shrinkage, insufficient contrast, movement of the sample and bubble formation during mounting or scanning. Here, we describe the preparation, stabilization, dehydration and mounting of large soft-tissue samples for X-ray microtomography. We detail the protocol applied to whole human organs and hierarchical phase-contrast tomography at the European Synchrotron Radiation Facility, yet it is applicable to a range of biological samples, including complete organisms. The protocol enhances the contrast when using X-ray imaging, while preventing sample motion during the scan, even with different sample orientations. Bubbles trapped during mounting and those formed during scanning (in the case of synchrotron X-ray imaging) are mitigated by multiple degassing steps. The sample preparation is also compatible with magnetic resonance imaging, computed tomography and histological observation. The sample preparation and mounting require 24-36 d for a large organ such as a whole human brain or heart. The preparation time varies depending on the composition, size and fragility of the tissue. Use of the protocol enables scanning of intact organs with a diameter of 150 mm with a local voxel size of 1 μm. The protocol requires users with expertise in handling human or animal organs, laboratory operation and X-ray imaging.
With the promising results of immunotherapy in patients with stage III melanoma, the role of adjuvant radiotherapy after resection and complete lymph-node dissection must be reassessed. We evaluate ...the outcomes and safety of adjuvant radiotherapy and immunotherapy compared to immunotherapy only in patients with resected stage III melanoma.
This retrospective and single institution study included patients treated for a stage III melanoma with complete lymph-node dissection and adjuvant immunotherapy from January 2019 to December 2022. The radiotherapy associated with immunotherapy group was defined by completion of immunotherapy and adjuvant radiotherapy in the lymph-node dissection area. The primary endpoint was disease-free survival. The secondary endpoints were locoregional progression, incidence of adverse events grade 3 or above and disease-free survival rate in patients with high risk of locoregional recurrence.
Thirty-three patients were included. Among them, twelve received adjuvant lymph-node field radiotherapy. The median duration of follow-up was 17months (range: 8–45months). Patients receiving radiotherapy and immunotherapy had a significantly higher disease stage and more frequent extracapsular extension. At 12months, the disease-free survival rate was 66.7% for the patients receiving immunotherapy alone (95% CI: 42.5–82.5%) and 83.3% for those receiving radiotherapy and immunotherapy (95% CI: 48.2–95.6%; P=0.131). The locoregional progression rate was 24% in patients receiving immunotherapy and 8% in patients receiving immunotherapy and radiotherapy (P=0.379). After adjuvant treatment, 6% of patients developed grade 3 or above immunotherapy-related events and none developed grade 3 or above radiation-related adverse events.
In patients with stage III melanoma, adjuvant lymph-node field radiotherapy combined with immunotherapy seems to be associated with longer disease-free survival, with acceptable tolerance. However, these results need to be confirmed by long-term and prospective studies.
Avec les résultats prometteurs de l’immunothérapie pour les patients atteints d’un mélanome de stade III, le rôle de la radiothérapie ganglionnaire adjuvante doit être réévalué. Dans cette étude rétrospective, nous avons étudié les résultats et la tolérance de l’association de radiothérapie adjuvante et de l’immunothérapie par rapport à l’immunothérapie seule pour les patients atteints d’un mélanome de stade III.
Cette étude monocentrique incluait tous les patients pris en charge pour un mélanome de stade III par résection, curage et immunothérapie adjuvante de janvier 2019 à décembre 2022. Le groupe radiothérapie avec immunothérapie était défini par la réalisation d’une irradiation dans la zone de curage. Le critère d’évaluation principal était la survie sans récidive. Les critères d’évaluation secondaires étaient la progression locorégionale, l’incidence des événements indésirables de grade 3 ou plus et la survie sans récidive pour les patients avec des critères de haut risque de récidive locorégionale.
Trente-trois patients ont été inclus. Parmi eux, douze ont reçu une radiothérapie adjuvante ganglionnaire. Les patients du groupe radiothérapie et immunothérapie avaient un stade de maladie plus évolué et une extension extracapsulaire plus fréquente. La durée médiane de suivi était de 17 mois (intervalle : 8–45 mois). À 12 mois, la probabilité de survie sans récidive était de 66,7 % pour les patients recevant l’immunothérapie seule (intervalle de confiance à 95 % IC95 % : 42,5–82,5 %), et de 83,3 % pour le groupe radiothérapie et immunothérapie (IC95 % : 48,2–95,6 % ; p=0,131). Les taux de récidive ganglionnaire étaient de 24 % chez les patients pris en charge par immunothérapie et de 8 % chez ceux recevant une radiothérapie et une immunothérapie (p=0,379). Les taux d’événements indésirables liés à l’immunothérapie, de grade 3 ou plus étaient de 6 %. Aucun patient n’a souffert d’événement indésirable de grade 3 ou plus secondaire à la radiothérapie.
Pour les patients atteints d’un mélanome de stade III, la radiothérapie adjuvante ganglionnaire associée à l’immunothérapie adjuvante semble être associée à une meilleure probabilité de survie sans récidive avec des effets secondaires acceptables. Cependant, ces résultats nécessitent être confirmés par des études randomisées prospectives.
Efficient ventilation is important during cardiopulmonary resuscitation (CPR). Nevertheless, there is insufficient knowledge on how the patient’s position affects ventilatory parameters during ...mechanically assisted CPR. We studied ventilatory parameters at different positive end-expiratory pressure (PEEP) levels and when using an inspiratory impedance valve (ITD) during horizontal and head-up CPR (HUP-CPR).
In this human cadaver experimental study, we measured tidal volume (VT) and pressure during CPR at different randomized PEEP levels (0, 5 or 10 cmH2O) or with an ITD. CPR was performed, in the following order: horizontal (FLAT), at 18° and then at 35° head-thorax elevation. During the inspiratory phase we measured the net tidal volume (VT) adjusted to predicted body weight (VTPBW), reversed airflow (RAF), and maximum and minimum airway pressure (Pmax and Pmin).
Using ten thawed fresh-frozen cadavers we analyzed the inspiratory phase of 1843 respiratory cycles, 229 without CPR and 1614 with CPR. In a mixed linear model, thoracic position and PEEP significantly impacted VTPBW (p < 0.001 for each), and the insufflation time, thoracic position and PEEP significantly affected the RAF (p < 0.001 for each) and Pmax (p < 0.001). For Pmin, only PEEP was significant (p < 0.001). In subgroup analysis, at 35° VTPBW and Pmax were significantly reduced compared with the flat or 18° position.
When using mechanical ventilation during CPR, it seems that the PEEP level and patient position are important determinants of respiratory parameters. Moreover, tidal volume seems to be lower when the thorax is positioned at 35°.
The aim of the study was to analyze the weaning success, the type of weaning procedures, and weaning duration in consecutive infants hospitalized in a pediatric intensive care unit over a winter ...season.
A retrospective observational study was conducted in a pediatric intensive care unit in a tertiary center. Infants hospitalized for severe bronchiolitis were included and the weaning procedure from continuous positive airway pressure (CPAP), noninvasive ventilation (NIV), or high-flow nasal cannula (HFNC) was analyzed.
Data from 95 infants (median age, 47 days) were analyzed. On admission, 26 (27%), 46 (49%), and 23 (24%) infants were supported with CPAP, NIV, and HFNC, respectively. Weaning failed in one (4%), nine (20%), and one (4%) infants while supported with CPAP, NIV, or HFNC, respectively (p = 0.1). In infants supported with CPAP, CPAP was stopped directly in five patients (19%) while HFNC was used as an intermediate ventilatory support in 21 (81%). The duration of weaning was shorter for HFNC (17 h, IQR: 0–26) than for CPAP (24 h, 14–40) and NIV (28 h, 19–49) (p < 0.01).
The weaning phase corresponds to a large proportion of noninvasive ventilatory support duration in infants with bronchiolitis. The weaning procedure following a “step-down” strategy may lead to an increase in the duration of weaning.
Mountainous areas pose a challenge for the out-of-hospital cardiac arrest (OHCA) chain of survival. Survival rates for OHCAs in mountainous areas may differ depending on the location. Increased ...survival has been observed compared to standard location when OHCA occurred on ski slopes. Limited data is available about OHCA in other mountainous areas. The objective was to compare the survival rates with a good neurological outcome of OHCAs occurring on ski slopes (On-S) and off the ski slopes (OffS) compared to other locations (OL).
Analysis of prospectively collected data from the cardiac arrest registry of the Northern French Alps Emergency Network (RENAU) from 2015 to 2021. The RENAU corresponding to an Emergency Medicine Network between all Emergency Medical Services and hospitals of 3 counties (Isère, Savoie, Haute-Savoie). The primary outcome was survival at 30 days with a Cerebral Performance Category scale (CPC) of 1 or 2 (1: Good Cerebral Performance, 2: Moderate Cerebral Disability).
A total of 9589 OHCAs were included: 213 in the On-S group, 141 in the Off-S group, and 9235 in the OL group. Cardiac etiology was more common in On-S conditions (On-S: 68.9% vs OffS: 51.1% vs OL: 66.7%, p < 0.001), while Off-S cardiac arrests were more often due to traumatic circumstances (OffS: 39.7% vs On-S: 21.7% vs OL: 7.7%, p < 0.001). Automated external defibrillator (AED) use before rescuers' arrival was lower in the Off-S group than in the other two groups (On-S: 15.2% vs OL: 4.5% vs OffS: 3.7%; p < 0.002). The first AED shock was longer in the Off-S group (median time in minutes: OffS: 22.0 (9.5–35.5) vs On-S: 10.0 (3.0–19.5) vs OL: 16.0 (11.0–27.0), p = 0.03). In multivariate analysis, on-slope OHCA remained a positive factor for 30-day survival with a CPC score of 1 or 2 with a 1.96 adjusted odds ratio (95% confidence interval (CI), 1.02–3.75, p = 0.04), whereas off-slope OHCA had an 0.88 adjusted odds ratio (95% CI, 0.28–2.72, p = 0.82).
OHCAs in ski-slopes conditions were associated with an improvement in neurological outcomes at 30 days, whereas off-slopes OHCAs were not. Ski-slopes rescue patrols are efficient in improving outcomes.
Purpose
The objective of this study was to identify the most appropriate cadaver perfusion techniques for surgical training through a systematic review with a description of the protocols used.
...Methods
The search strategy included PubMed and reference tracking. Studies were identified by searching the electronic Medline databases. The search concepts included perfusion, cadavers and simulation training, and the protocol used is reported. This resulted in a qualitative review of 12 articles out of 250 articles consulted. We collected all the important data from these 12 articles.
Results
Regarding the characteristics of the studies and the declotting or perfusion techniques, the results were heterogeneous. Indeed, in several studies, a good deal of information was unclear or insufficiently precise, making it unfeasible to summarize the data. The methods used were not sufficiently explicit and detailed. However, a majority of the fresh cadavers used tap water for declotting. Perfusion, type of fluid, number of pumps, pressure, pulsatility, and arterial or venous approaches differed greatly. Only two studies fulfilled five of our six realism criteria for surgical simulation.
Conclusions
This systematic review provided an overview of all the different cadaver perfusion techniques. It could be used to establish a reference method of a simulation model.
To provide an overview of cadaver models for cardiac arrest and to identify the most appropriate cadaver model to improve cardiopulmonary resuscitation through a systematic review.
The search ...strategy included PubMed, Embase, Current contents, Pascal, OpenSIGLE and reference tracking. The search concepts included “heart arrest”, “cardiopulmonary resuscitation” and “cadavers”. All studies, published until February 2019, in English or French, on research or simulation in the field of cardiac arrest and using cadaver models were eligible for inclusion.
Overall, 29 articles out of the 244 articles located were selected. The characteristics of the studies and the cadaver models were heterogenous. Indeed, 31% of the studies lacked a proper description of the model used and its specificities. Fresh cadavers were used in 55% of the studies and chest compressions were performed in 90%. This model was appreciated for its realism in terms of mechanical properties and tissue conservation. Thiel-embalmed cadavers also showed promising results concerning lung and chest compliance. The lack of circulation stood out as the strongest limitation of all types of human cadaver models.
Four types of cadaver models are used in cardiac arrest research. The great heterogeneity of these models coupled with unequal quality in reporting makes comparisons between studies difficult. There is a need for uniform reporting and standardisation of human cadaver models in cardiac arrest research.
Purpose
Dissection provides direct experience in anatomy, which constitutes an essential discipline for medical students. For this purpose, we created a dissection guide for students in the 2nd-year ...of medical studies at the Grenoble University School of Medicine. The objective was to evaluate this tool of reverse pedagogy in terms of student satisfaction and educational interest.
Methods
Every 2nd-year student takes four sessions of limb dissection. To assist this dissection course, we developed a photographic guide launched in 2013. It includes an introduction presenting a methodology for dissection, followed by detailed protocols for each dissection area. Each step is illustrated with captioned photographs associated with a concise explanatory text. A questionnaire was then sent to 242 students to assess the impact of this tool and their overall satisfaction.
Results
Overall student satisfaction with this guidebook was rated 8.1 out of 10 with a 93.2% with significant improvement (
p
= 0.0137) and 78.7% of them declaring they had a better understanding of anatomy and mastery of the dissection techniques, respectively. In addition, students assessed the usefulness of the dissection guide at 3.6 out of 4 with the relevance of the content and presentation judged at 3.4 out of 4. Finally, the exam scores increased significantly with use of the guidebook (
p
< 0.0001).
Conclusions
Students deemed the organization of this anatomy tutorial as highly satisfactory, and using the guidebook as a reference in dissection sessions allowed students to prepare for the dissection and improve their knowledge of anatomy, as demonstrated by improved exam scores.