Ion recombination correction factors and detector comparison in a very-high dose rate proton scanning beam.

PURPOSE: Accurate dosimetry is paramount to study the FLASH biological effect since dose and dose rate are critical dosimetric parameters governing its underlying mechanisms. With the goal of assessing the suitability of standard clinical dosimeters in a very-high dose rate (VHDR) experimental setup, we evaluated the ion collection efficiency of several commercially available air-vented ionization chambers (IC) in conventional and VHDR proton irradiation conditions. METHODS: A cyclotron at the Orsay Proton Therapy Center was used to deliver VHDR pencil beam scanning irradiation. Ion recombination correction factors (ks) were determined for several detectors (Advanced Markus, PPC05, Nano Razor, CC01) at the entrance of the plateau and at the Bragg peak, using the Niatel model, the Two-voltage method and Boag's analytical formula for continuous beams. RESULTS: Mean dose rates ranged from 4 Gy/s to 385 Gy/s, and instantaneous dose rates up to 1000 Gy/s were obtained with the experimental set-up. Recombination correction factors below 2 % were obtained for all chambers, except for the Nano Razor, at VHDRs with variations among detectors, while ks values were significantly smaller (0.8 %) for conventional dose rates. CONCLUSIONS: While the collection efficiency of the probed ICs in scanned VHDR proton therapy is comparable to those in the conventional regime with recombination coefficiens smaller than 1 % for mean dose rates up to 177 Gy/s, the reduction in collection efficiency for higher dose rates cannot be ignored when measuring the absorbed dose in pre-clinical proton scanned FLASH experiments and clinical trials.

Secondary neutron dose contribution from pencil beam scanning, scattered and spatially fractionated proton therapy.

The Orsay Proton therapy Center (ICPO) has a long history of intracranial radiotherapy using both double scattering (DS) and pencil beam scanning (PBS) techniques, and is actively investigating a promising modality of spatially fractionated radiotherapy using proton minibeams (pMBRT). This work provides a comprehensive comparison of the organ-specific secondary neutron dose due to each of these treatment modalities, assessed using Monte Carlo (MC) algorithms and measurements. A MC model of a universal nozzle was benchmarked by comparing the neutron ambient dose equivalent,H*(10), in the gantry room with measurements obtained using a WENDI-II counter. The secondary neutron dose was evaluated for clinically relevant intracranial treatments of patients of different ages, in which secondary neutron doses were scored in anthropomorphic phantoms merged with the patients' images. The MC calculatedH*(10) values showed a reasonable agreement with the measurements and followed the expected tendency, in which PBS yields the lowest dose, followed by pMBRT and DS. Our results for intracranial treatments show that pMBRT yielded a higher secondary neutron dose for organs closer to the target volume, while organs situated furthest from the target volume received a greater quantity of neutrons from the passive scattering beam line. To the best of our knowledge, this is the first study to compare MC secondary neutron dose estimates in clinical treatments between these various proton therapy modalities and to realistically quantify the secondary neutron dose contribution of clinical pMBRT treatments. The method established in this study will enable epidemiological studies of the long-term effects of intracranial treatments at ICPO, notably radiation-induced second malignancies.

Comparable clinical and functional outcomes after anterior cruciate ligament reconstruction over and under 40 years of age.

PURPOSE: The aim of the present meta-analysis was to update the literature on the outcomes and complications of ACL reconstruction in patients aged 40 years and older. It has been hypothesized that patients older than 40 years of age may have comparable clinical outcomes to those of younger patients. METHODS: A systematic review of articles from 1996 to 2018 was completed using Pubmed, Medline, Cochrane Reviews, and Google Scholar databases using the keyword terms "anterior cruciate ligament reconstruction" and "middle-aged OR elderly OR over 40 OR age factors." Functional and clinical outcomes (International Knee Documentation Committee, Lysholm and Tegner score and KT-1000 arthrometer), complication and graft failure rate were evaluated. RESULTS: Eleven articles met inclusion criteria. In total, 306 middle-aged patients and 566 younger patients were included in this study. The mean age of patients > 40 was 49 ± 7 (range 40-75) years with a mean follow-up of 25 ± 9 months (range 12-68). The mean age of younger patients was 26 ± 2.7 (range 15-39) years with a mean post-operative follow-up of 26.7 ± 11.5 months (range 3-64). The results were slightly higher (but no significantly different) towards the younger group in terms of objective IKDC (P = n.s.), Lysholm (P = n.s.) and Tegner (P = n.s.) scores and knee laxity assessment (P = n.s.). Complication rate (P = n.s.) and graft failure (P = n.s.) were low even in this cohort. CONCLUSIONS: The present meta-analysis shows that patients older than 40 years achieve comparable clinical outcomes to those of younger patients following primary ACL reconstruction. This evidence may push the surgeons toward a more aggressive approach in this specific cohort of patients. LEVEL OF EVIDENCE: III.

The cutaneous microvascular architecture of human diabetic toe studied by corrosion casting and scanning electron microscopy analysis.

In this morphological study, we report on the three-dimensional microvascular architecture constituting the toes of a patient affected by diabetic microangiopathy. We applied corrosion casting (CC) technique to the toes of a patient affected by Type 2 diabetes, who underwent surgery for explantation of inferior left limb due to necrotic processes of soft tissues. The toes of a foot traumatically explanted in a motorcycle accident were kept as controls. According to technical protocols, toes were injected with a low-viscosity acrylic resin (Mercox) through the major digital artery, tissues were corroded in KOH solution (8%), and resulting casts processed for SEM observations. Already at low magnification, in diabetic toes, we found an impairment of the linear track-like disposition of the vessels of plantar side, with signs of vascular disruption and obliterations, stopped resin, and leakages. Capillaries under the nail and a lot of vascular villi in eponychium and nail borders were damaged, and vascular regression phenomena acting on them were clearly visible. Resin leakages and impairment of normal vascular architecture were also observed in the root of the nail. This preliminary report represents only the first step for further investigations regarding morphological three-dimensional appearance of diabetic microangiopathy. CC and scanning electron microscopy technique well documented these morphological modifications, highlighting on both structural and ultrastructural features of diabetic toes microvessels. In conclusion, our qualitative data try to better focus on the pathophysiological mechanisms involved in diabetic dermopathy and microangiopathy, proposing CC as useful method to investigate on them.

Biomechanics of the goat three bundle anterior cruciate ligament.

The goat is a widely used animal model for basic research on the anterior cruciate ligament (ACL), but the biomechanical role of the different bundles [intermediate (IM), anteromedial (AM), posterolateral (PL)] of the ACL is unclear. Therefore, the aim of this study is to describe the biomechanical function of the different bundles and evaluate its use for a double bundle ACL reconstruction model. A CASPAR Stäubli RX90 robot with a six degree-of-freedom load cell was used for measurement of anterior tibial translation (ATT) (mm) and in situ forces (N) at 30 degrees (full extension), 60 degrees , 90 degrees as well as rotational testing at 30 degrees in 14 paired goat knees before and after each bundle was cut. When the AM-bundle was cut, the ATT increased significantly at 60 degrees and 90 degrees of flexion (p < 0.05). When the PL-bundle was cut, the ATT increased only at 30 degrees. However, most load was transferred through the big AM-bundle while the PL-bundle shared significant load only at 30 degrees, with only minimal contribution from the IM-bundle at all flexion degrees. The observed biomechanical results in this study are similar to the human ACL observed previously in the literature. Though anatomically discernible, the IM-bundle plays only an inferior role in ATT and might be neglected as a separate bundle during reconstruction. The goat ACL shows some differences to the human ACL, whereas the main functions of the ACL bundles are similar.

Gait analysis of pre- and post-meniscectomy knee: a prospective study.

Degenerative changes in the knee joint after meniscectomy are well known. Although likely to be due to changed biomechanics, there is no evidence in the literature to identify the underlying biomechanical alterations. The aim of this study was to analyse lower limb gait biomechanics before and after meniscectomy. Ten patients who required partial medial meniscectomy for irreparable meniscal tear took part in motion analysis before surgery, then at 6 and 12 months post-operatively. A control group was also set up consisting of 10 healthy volunteers. Joint kinematics did not show significant alterations between pre-operative and 6 month post-operative evaluations. However flexion increases at the hip, knee and ankle joint were observed in late swing and early stance phase 12 months after surgery. Hip and knee flexion-extension moments were affected with knee moment altered both before and after surgery. Before surgery and at 6 months after, the changes occurred mainly at the point of push off, while at 12 months they occurred during the swing phase. Hip flexion-extension moment had also changed 12 months after surgery. When examining symmetry of gait patterns prior to surgery, there were differences between the flexion-extension moments of the healthy and of the injured knee at first impact and during late stance. After surgery, asymmetries were not more apparent at first impact, but in late stance phase a reduced knee extension moment in the injured limb was still present. Before surgery, the joint kinematics were not greatly altered and changes were mainly due to pain. After partial meniscectomy, the pain disappeared and new joint responses were observed. These could be caused by the altered mechanics and/or through proprioceptive mechanisms.

Follow-up of collagen meniscus implants by MRI.

PURPOSE: The purpose of our study was to evaluate the usefulness of magnetic resonance imaging (MRI) in the follow-up of patients treated with collagen meniscus implant (CMI) and to identify MRI patterns suitable for defining its evolution. MATERIALS AND METHODS: Between March 2001 and June 2003, CMI was performed on 40 patients (27 men and 13 women, age 23-58 years, median 41 years) affected by irreparable medial meniscal lesions. All patients underwent MRI follow-up at 6 months and 1 year and 16 patients 2 years after the operation; 12 patients underwent second-look arthroscopy with implant biopsy. All MRI examinations were performed with a 1.5-T unit using GE T2*, spin-echo (SE) T1, and FatSat fast spin-echo (FSE) DP and T2-weighted sequences, with different orientations. At 24 months, MR arthrography was also performed. Implant evolution was assessed on the basis of MRI direct and indirect criteria. Direct criteria were morphology and signal intensity of the collagen meniscus/residual meniscus complex. Based on these characteristics, three pattern were identified and classified from 1 to 3, where a higher score corresponded to characteristics approaching those of the normal meniscus. Indirect criteria were chondral surface and subchondral bone marrow oedema at implant site and associated synovial pathology. RESULTS: MRI follow-up at 6 months showed CMI shape and size to be normal (type 3) in 35/40 patients and type 2 in 5/40 patients. CMI signal intensity was type 1 in 32/40 patients and type 2 in 8/40. An interface between prosthetic and native meniscus was identified in 27/40 patients. Chondral lesions were present in 3/40 cases and subchondral bone marrow oedema in 8/40 cases. Reactive synovial effusion was seen in 2/40 patients. MRI follow-up at 12 months showed CMI shape and size to be normal (type 3) in 33/40 patients and type 2 in 7/40. Signal intensity was type 1 in 14/40 patients and type 2 in 26/40 patients. The interface was seen in 19/40 patients. The associated chondral lesions were unchanged, whereas subchondral bone marrow oedema was present in 3/40 patients. No synovial reaction was detected. At 24 months, CMI size was type 3 in 9/16 patients, type 2 in 6/16, and type 1 in one patient in whom the implant could not be identified, as it had been totally resorbed. CMI signal intensity was type 2 in 11/15 and type 3 in 4/16. The interface was identified in seven patients. MR arthrography depicted two additional chondral lesions and enabled correct grading of all lesions. Subchondral bone marrow oedema was present in two patients only. CONCLUSIONS: MRI enables morphological and structural changes of CMI to be monitored over time. Follow-up can be extended beyond 2 years, until the CMI has stabilised and subchondral bone marrow oedema has completely resolved. In the single case with a poor CMI outcome, no related direct or indirect signs were identified.

Plexiform vascular structures in the human digital dermal layer: a SEM--corrosion casting morphological study.

This study aimed to describe the impressive diversity of vascular plexiform structures of the hypodermal layer of human skin. We chose the human body site with the highest concentration of dermal corpuscles, the human digit, and processed it with the corrosion casting technique and scanning electron microscopy analysis (SEM). This approach proved to be the best tool to study these microvascular architectures, free from any interference by surrounding tissues. We took high-definition pictures of the vascular network of sweat glands, thermoreceptorial and tactile corpuscles, the vessels constituting the glomic bodies and those feeding the hair follicles. We observed that the three-dimensional disposition of these vessels strictly depends on the shape of the corpuscles supplied. We could see the tubular vascularization of the excretory duct of sweat glands and the ovoid one feeding their bodies, sometimes made up of two lobes. In some cases, knowledge of these morphological data regarding the normal disposition in space and intrinsic vascularization structure of the dermal corpuscles can help to explain many of the physiopathological changes occurring during chronic microangiopathic diseases.

Autologous chondrocyte implantation using a bilayer collagen membrane: a preliminary report.

OBJECTIVE: To present preliminary clinical experience with Matrix-induced autologous chondrocyte implantation, a new tissue-engineering technique for treatment of deep cartilage defects, in which autologous chondrocytes are seeded on a tridimensional scaffold provided by a bilayer type I-III collagen membrane. METHODS: From December 1999 to January 2001, 13 patients underwent implantation procedure for deep cartilage defects. Age of patients ranged from 18 to 49 years (mean age, 35 years). The mean defect size was 3.5 cm(2) (range, 2.0-4.5 cm(2)). Clinical and functional evaluation were performed using various score systems for the ankle and the knee, and magnetic resonance imaging was performed at 6 and 12 months postoperatively. Membrane structure and cellular population were investigated by light microscopy, scanning electron microscopy, and electrophoresis before implantation. RESULTS: The mean follow-up was 6.5 months (range, 2-15 months). No complications were observed in the postoperative period. The 6 patients with a minimum follow-up of 6 months showed an improvement in clinical and functional status after surgery. Magnetic resonance images showed the presence of hyaline-like cartilage at the site of implantation; there was evidence of chondroblasts and type II collagen inside the seeded membrane. CONCLUSION: Matrix-induced autologous chondrocyte implantation offers several advantages with respect to the traditional cultured cell procedure. These include technical simplicity, short operating time, minimal invasiveness, and easier access to difficult sites. It appears to be a reliable method for the repair of deep cartilage defects.