Introduction. Trabecular bone score (TBS) is a parameter of bone microarchitecture that is determined by the level analysis of DXA images. TBS is associated with fractures in the preliminary case-control and prospective studies. The aim of this study was to assess the TBS role in the traumatology and orthopedics. Materials and methods. We've examined 176 healthy women aged 40–79 years (mean age – 53.4±0.6 yrs) and 117 men aged 40–79 years (mean age – 59.8±0.9 yrs). Bone mineral density (BMD) of whole body, PA lumbar spine and proximal femur were measured by DXA method (Prodigy, GEHC Lunar, Madison, WI, USA) and PA spine TBS were assessed by TBS iNsight® software package installed on the available DXA machine (Med-Imaps, Pessac, France). Results. We have observed a significant decrease of TBS as a function of age (F=6.56; p=0.0003) whereas PA spine BMD was significantly increasing with age (F=4.04; p=0.008) in the examined women. This contradiction can be traced to the spinal osteoarthritis and degenerative diseases progressing with age in the elderly patients. TBS was significantly lower in women with duration of PMP over 4 yrs (p=0.003) in comparison with women without menopause; BMD of spine significantly decreased in women with duration of PMP over 7–9 yrs (p=0.02). So, the TBS can detect changes in the state of bone tissue at the earlier stage than BMD. We have observed a significant decrease of TBS in men with ageing (F=2.44; p=0.05). Overall TBS values in men are lower than the age matched TBS values in women. Conclusion. TBS is an independent parameter which has a potential diagnostic value of its own, without taking into account the BMD results. The study concerning patients with osteoporosis and fractures is underway

Osteoarthritis (OA) is a disabling disease depriving the quality of life of patients. Mesenchymal stem cells (MSCs) are recently used to modify the inflammatory and degenerative cascade of the disease. Source of MSCs could change the progression and symptoms of OA due to their different metabolomic activities. We asked whether MSCs derived from the infrapatellar fat (IPF), synovium (Sy) and subcutaneous (SC) tissues will decrease inflammatory and degenerative markers of normal and OA chondrocytes and improve regeneration in culture. Tissues were obtained from three male patients undergoing arthroscopic knee surgery due to sports injuries after ethical board approval. TNFa concentration decreased in all MSC groups (Sy=156,6±79, SC=42,1±6 and IPF=35,5±3 pg/ml; p=0,036) on day 14 in culture. On day seven (Sy=87,4±43,7, SC=23±8,9 and IPF=14,7±3,3 pg/ml, p=0,043) and 14 (Sy=29,1±11,2, SC=28,3±18,5 and IPF=20,3±16,2 pg/ml, p=0,043), MMP3 concentration decreased in all groups. COMP concentration changes however were not significant. Plot scores of tissues for PC2-13,4% were significantly different. Based on the results of liquid chromatography-mass spectrometry (LC-MS) metabolomics coupled with recent data processing strategies, clinically relevant seven metabolites (L-fructose, a-tocotrienol, coproporphyrin, nicotinamide, bilirubin, tauro-deoxycholic acid and galactose-sphingosine) were found statistically different (p<0.05 and fold change>1.5) ratios in tissue samples. Focusing on these metabolites as potential therapeutics could enhance MSC therapies. Acknowledgment: Hacettepe University, Scientific Research Projects Coordination Unit (#THD-2020-18692) and Turkish Society of Orthopedics and Traumatology (#TOTBID-89) funded this project. Feza Korkusuz MD is a member of the Turkish Academy of Sciences (TÜBA)

Spinal surgery deals with the treatment of different pathological conditions of the spine such as tumors, deformities, degenerative disease, infections and traumas. Research in the field of vertebral surgery can be divided into two main areas: 1) research lines transversal to the different branches; 2) specific research lines for the different branches. The transversal lines of research are represented by strategies for the reduction of complications, by the development of minimally invasive surgical techniques, by the development of surgical navigation systems and by the development of increasingly reliable systems for the control of intra-operative monitoring. Instead, specific lines of research are developed within the different branches. In the field of oncological pathology, the current research concerns the development of in vitro models for the study of metastases and research for the study of targeted treatment methods such as electrochemotherapy and mesenchymal stem cells for the treatment of aneurysmal bone cysts. Research in the field of spinal deformities is focused on the development of increasingly minimally invasive methods and systems which, combined with appropriate pharmacological treatments, help reduce trauma, stress and post-operative pain. Scaffolds based on blood clots are also being developed to promote vertebral fusion, a fundamental requirement for improving the outcome of vertebral arthrodesis performed for the treatment of degenerative disc disease. To improve the management and the medical and surgical treatment of vertebral infections, research has focused on the definition of multidisciplinary strategies aimed at identifying the best possible treatment path. Thus, flow-charts have been created which allow to manage the patient suffering from vertebral infection. In addition, dedicated silver-coated surgical instrumentation and bone substitutes have been developed that simultaneously guarantee mechanical stability and reduce the risk of further local infection. In the field of vertebral traumatology, the most recent research studies have focused on the development of methods for the biostimulation of the bone growth in order to obtain, when possible, healing without surgery. Methods have also been developed that allow the minimally invasive percutaneous treatment of fractures by means of vertebral augmentation with PMMA, or more recently with the use of silicone which from a biomechanical point of view has an elastic modulus more similar to that of bone. It is clear that scientific research has changed clinical practice both in terms of medical and surgical management of patients with spinal pathologies. The results obtained stimulate the basic research to achieve even more. For this reason, new lines of research have been undertaken which, in the oncology field, aim at developing increasingly specific therapies against target receptors. Research efforts are also being multiplied to achieve regeneration of the degenerated intervertebral disc and to develop implants with characteristics increasingly similar to those of bone in order to improve mechanical stability and durability over time. Photodynamic therapies are being developed for the treatment of infections in order to reduce the use of antibiotic therapies. Finally, innovative lines of research are being launched to treat and regenerate damaged nerve structures with the goal, still far from today, of making patients with spinal cord injuries to walk

Open limb fractures are typically due to a high energy trauma. Several recent studied have showed treatment's superiority when a multidisciplinary approach is applied. World Health Organization reports that isolate limb traumas have an incidence rate of 11.5/100.000, causing high costs in terms of hospitalization and patient disability. A lack of experience in soft tissue management in orthopaedics and traumatology seems to be the determining factor in the clinical worsening of complex cases. The therapeutic possibilities offered by microsurgery currently permit simultaneous reconstruction of multiple tissues including vessels and nerves, reducing the rate of amputations, recovery time and preventing postoperative complications. Several scoring systems to assess complex limb traumas exist, among them: NISSSA, MESS, AO and Gustilo Anderson. In 2010, a further scoring system was introduced to focus open fractures of all locations: OTA-OFC. Rather than using a single composite score, the OTA-OFC comprises five components grades (skin, arterial, muscle, bone loss and contamination), each rated from mild to severe. The International Consensus Meeting of 2018 on musculoskeletal infections in orthopaedic surgery identified the OTA-OFC score as an efficient catalogue system with interobserver agreement that is comparable or superior to the Gustilo-Anderson classification. OTA-OFC predicts outcomes such as the need for adjuvant treatments or the likelihood of early amputation. An orthoplastic approach reconstruction must pay adequate attention to bone and soft tissue infections management. Concerning bone management: there is little to no difference in terms of infection rates for Gustilo-Anderson types I–II treated by reamed intramedullary nail, circular external fixator, or unreamed intramedullary nail. In Gustilo-Anderson IIIA-B fractures, circular external fixation appears to provide the lowest infection rates when compared to all other fixation methods. Different technique can be used for the reconstruction of bone and soft tissue defects based on each clinical scenario. Open fracture management with fasciocutaneous or muscle flaps shows comparable outcomes in terms of bone healing, soft tissue coverage, acute infection and chronic osteomyelitis prevention. The type of flap should be tailored based on the type of the defect, bone or soft tissue, location, extension and depth of the defect, size of the osseous gap, fracture type, and orthopaedic implantation. Local flaps should be considered in low energy trauma, when skin and soft tissue is not traumatized. In high energy fractures with bone exposure, muscle flaps may offer a more reliable reconstruction with fewer flap failures and lower reoperation rates. On exposed fractures several studies report precise timing for a proper reconstruction. Hence, timing of soft tissue coverage is a critical for length of in-hospital stay and most of the early postoperative complications and outcomes. Early coverage has been associated with higher union rates and lower complications and infection rates compared to those reconstructed after 5-7 days. Furthermore, early reconstruction improves flap survival and reduces surgical complexity, as microsurgical free flap procedures become more challenging with a delay due to an increased pro-thrombotic environment, tissue edema and the increasingly friable vessels. Only those patients presenting to facilities with an actual dedicated orthoplastic trauma service are likely to receive definitive treatment of a severe open fracture with tissue loss within the established parameters of good practice. We conclude that the surgeon's experience appears to be the decisive element in the orthoplastic approach, although reconstructive algorithms may assist in decisional and planification of surgery

Treatment of large bone defects represents a great challenge for orthopedic surgeons. The main causes are congenital abnormalities, traumas, osteomyelitis and bone resection due to cancer. Each surgical method for bone reconstruction leads its own burden of complications. The gold standard is considered the autologous bone graft, either of cancellous or cortical origin, but due to graft resorption and a limitation for large defect, allograft techniques have been identified. In the bone defect, these include the placement of cadaver bone or cement spacer to create the ‘Biological Chamber’ to restore bone regeneration, according to the Masquelet technique. We report eight patients, with large bone defect (for various etiologies and with an average size defect of 13.3 cm) in the lower and upper limbs, who underwent surgery at our Traumatology Department, between January 2019 and October 2020. Three patients were treated with both cortical and cancellous autologous bone grafts, while five received cortical or cement spacer allografts from donors. They underwent pre and postoperative radiographs and complete osseointegration was observed in all patients already undergoing monthly radiographic checks, with a restoration of length and range of motion. In our study, both the two stage-Masquelet and the cortical bone graft from a cadaver donor proved to be valid techniques in patients with very extensive defects to reconstruct the defect, restore the length, minimize implant left in situ and achieve complete functional recovery

Introduction and Objective. Virtual Surgical Planning (VSP) is becoming an increasingly important means of improving skills acquisition, optimizing clinical outcomes, and promoting patient safety in orthopedics and traumatology. Pediatric Orthopedics (PO) often deals with the surgical treatment of congenital or acquired limbs and spine deformities during infancy. The objective is to restore function, improve aesthetics, and ensure proper residual growth of limbs and spine, using osteotomies, bone grafts, age-specific or custom-made hardware and implants. Materials and Methods. Three-dimensional (3D) digital models were generated from Computed Tomography (CT) scans, using free open-source software, and the surgery was planned and simulated starting from the 3D digital model. 3D printed sterilizable models were fabricated using a low-cost 3D printer, and animations of the operation were generated with the aim to accurately explain the operation to parents. All procedures were successfully planned using our VSP method and the 3D printed models were used during the operation, improving the understanding of the severely abnormal bony anatomy. Results. The surgery was precisely reproduced according to VSP and the deformities were successfully corrected in eight cases (3 genu varum in Blount disease, 2 coxa vara in pseudo achondroplasia, 1 SCFE, 1 missed Monteggia lesion and 1 post-traumatic forearm malunion deformity). In one case, a focal fibrocartilaginous dysplasia, the intraoperative intentional undersizing of the bone osteotomy produced an incomplete correction of a congenital forearm deformity. Conclusions. Our study describes the application of a safe, effective, user-friendly, VSP process in PO surgery. We are convinced that our study will stimulate the widespread adoption of this technological innovation in routine clinical practice for the treatment of rare congenital and post-traumatic limb deformities during childhood

Introduction and Objective. Management of bone loss associated with bone contamination or infection represents a double biological and clinical challenge frequent in traumatology. The advent of new biomaterials can allow a different approach in the treatment of bone gap. The purpose of this study was to evaluate the prophylactic and therapeutic effectiveness of addition of a new absorbable bone substitute (BS) eluting different antibiotics in reconstruction of bone defects after infections and fractures with soft tissue damage. Materials and Methods. We conducted a review of patients with contaminated or infected bone defects treated using a new biomaterial, a porous composite of collagen matrices and Beta tricalcium phosphate (β TCP), able to provide a long-term release of different antibiotics. We have included treatment of osteomyelitis and osteosynthesis of exposed fracture (Gustilo Anderson 1–3b) or fractures with soft tissue damage and high risk of contamination. Surgical technique included debridement filling bone defect with BS eluting antibiotics, osteosynthesis (plate, nail, external fixator, kirschner wire), soft tissue coverage, and systemic antibiotic therapy. Radiographic and clinical data including complications (wound dehiscence, superficial or deep infection, osteomyelitis) were collected. Results. We treated 25 patients (21 male, 4 female) with mean age 47 yrs. (range 21–83). The locations treated (for incidence) was: 9 femurs (7 plates, 2 nail), 7 calcanei (one bilateral), 3 tibias, 2 forearms, 2 metatarsi, 2 hands, 1 elbow. 6 patients had large bone loss. 7 patients had bone infections (4 were Cierny Madern 4); 8 patients had osteosynthesis of exposed fractures Gustilo Anderson 1–3b (9 plate, one bilateral calcaneus). 8 patients had treatment for pseudoarthrosis of exposed fractures (6 femurs, 1 forearm, 1 metatarsus) and 3 patients a prophylactic treatment for calcaneal fractures with soft tissue damage. 4 deep infection were treated with multiple surgical debridement and new filling bone defect with BS eluting antibiotic with infection eradication. We have used a combination of vancomycin and gentamicin on 15 cases, vancomycin alone on 4 cases, combination of vancomycin and amikacin on 1 case and amikacin and Linezolid in a targeted multi drug resistance. At final follow-up functional outcome was good in all cases with bone healing. Conclusions. Extensive debridement is a fundamental requisite for eradication of bone infections and contamination. Filling of the bone void with loaded bio-composite eluting diversifiable local antibiotics with synergistic anti-biofilm activity is desirable. Treatment of this bone defects are advantaged when combining his reconstruction with BS and the possibility of release high antibiotic concentration at least for 10 days. This is an important complementing prophylactic and therapeutic antimicrobial option with adjuvant role to systemic therapy that enlarges the success rate

Artificial bone models (ABMs) are commonly used in traumatology and orthopedics for training, education, research and development purposes. The aim of this study was to develop the first evidence-based generic Asian pelvic bone model and compare it to an existing pelvic model. A hundred clinical CT scans of intact adult pelvises (54.8±16.4 years, 161.3±8.3 cm) were acquired. They represented evenly distributed female and male patients of Malay (n=33), Chinese (n=34) and Indian (n=33) descent. The CTs were segmented and defined landmarks were placed. By this means, 100 individual three-dimensional models were calculated using thin plate spline transformation. Following, three statistical mean pelvic models (male, female, unisex) were generated. Anatomical variations were analyzed using principal component analysis (PCA). To quantify length variations, the distances between the anterior superior iliac spines (ASIS), the anterior inferior iliac spines (AIIS), the promontory and symphysis (conjugate vera) as well as the ischial spines (diameter transversa) were measured for the three mean models and the existing ABM. PCA demonstrated large variability regarding pelvic surface and size. Principal component one (PC 1) contributed to 24% of the total anatomical variation and predominantly displayed a size variation pattern. PC 2 (17.7% of variation) mainly exhibited anatomical variations originating from differences in shape. Female and male models were similar in ASIS (225±20 mm; 227±13 mm) and AIIS (185±11 mm; 187±10 mm), whereas differed in conjugate vera (116±10 mm; 105±10 mm) and diameter transversa (105±7 mm; 88±8 mm). Comparing the Asian unisex model to the existing ABM, the external pelvic measurements ASIS (22.6 cm; 27.5 cm) and AIIS (186 mm; 209 mm) differed notably. Conjugate vera (111 mm; 105 mm) and diameter transversa (97 mm; 95 mm) were similar in both models. Low variability of mean distances (3.78±1.7 mm) was found beyond a sample number of 30 CTs. Our analysis revealed notable anatomical variations regarding size dominating over shape and gender-specific variability. Dimensions of the generated mean models were comparatively smaller compared to the existing ABM. This highlights the necessity for generation of Asian ABMs by evidence-based modeling techniques

Abstract. Background. Proximal fibular osteotomy (PFO) was defined to provide a treatment option for knee pain caused by gonarthrosis(1). Minor surgical procedure, low complication rate and dramatic pain relief were the main reasons for popularization of this procedure(2, 3). However, changes at the knee and ankle joint after PFO were not clarified objectively in the literature. Questions/purposes. We asked: 1) Does PFO change the maximum and average pressures at the medial and lateral chondral surface of the tibia plateau? 2) Are chondral surface stresses redistributed at the knee and ankle joint after PFO? 3)Does PFO change the distribution of total load on the knee joint? 4) Can PFO lead to change in alignment of lower limb?. Methods. This study was conducted at Maltepe University Faculty of Medicine Hospital, Orthopedics and Traumatology Department and Yildiz Technical University Mechanical Engineering Department in Istanbul, Turkey, between September 2019 and February 2020. Finite element analysis (FEA) was used to evaluate effects of PFO(4). One 62 years old, female volunteer's X-ray, computer tomography and magnetic resonance imaging images were used for creating right lower limb model. Two different lower limb models were created. One of them was osteotomized model (OM) which was created according to definition of PFO and the other was non-osteotomized model (NOM). To obtain a stress distribution comparison between the two models, 350 N of axial force was applied to the femoral heads of the models. Results. After PFO, the maximum contact pressures at the medial and lateral tibial cartilages decreased 83.2% and 66.9%, respectively at the knee joint. The average contact pressure decreased 26.1% at the medial tibial cartilage and increased 42.4% at the lateral tibial cartilage. The Von Mises stresses decreased 57.1% at the femoral cartilage and decreased 79.1% at tibial cartilage. The stress on the tibial cartilage increased 44.6%, and stress on the talar cartilage increased 7.1% at the ankle joint. Under a 350 N axial force, distribution of the total load at the knee joint was changed and become more homogenous in OM compared to NOM. Change in lower extremity alignment after PFO could not be evaluated with FEA. Conclusion. FEA revealed that PFO causes some changes in knee and ankle joint kinematics. Main loading at the knee joint shifted from medial tibial cartilage to the lateral tibial cartilage after PFO. Additionally, the stresses on each cartilage were redistributed across a wider and more peripheral area. These changes could be the main reason for pain relief at the knee joint. FEA also demonstrated that the Von Mises stresses of the tibial and talar cartilages of the ankle joint increased after PFO. This stress increase may cause long-term arthritic changes in the ankle joint. Level IV; in silico study

Distraction histogenesis (DH) techniques have been widely accepted and practiced in orthopaedics, traumatology, and craniofacial surgery over the last two decades. Using DH methods, many previously untreatable conditions have been successfully managed with outstanding clinical outcomes. The biological mechanisms underlying DH have been studied and the tension-stress principles of tissue regeneration are attributed to upregulated gene expression, enhanced cell proliferation, angiogenesis and tissue remodelling and endogenous stem cell mobilization. The new methods of enhancing bone consolidation in DH are proposed and need further clinical studies. The novel applications of DH have now been extended for the treatment of vascular diseases, cranial defect (with neuronal disorders), hip and spinal deformity corrections and soft-tissue defects in addition to various bone defects and deformities. There are more surprises and novel mechanisms yet to be discovered for these novel applications of DH

Recently in traumatology various methods of impregnation biodegradable implants and allografts with antibiotics are widely used. Among them the soaking, shaking and ionophores are common used. We aimed to choose the optimal method of impregnation with the antibiotic of the head of the femur, taken from patients after arthroplasty. We studied 6 femoral heads after hip replacement. Head №1 the iohexol (Omnipaque) was injected through circular ligament and through the neck of the femur. Head №2 through the circular ligament, head №3 through the neck of the femur, head №4 through the circular ligament and through the neck of the femur, head №5 through 4 pre-drilled channels a brilliant green solution was injected. The head №6 was soaked in a brilliant green solution. Head №1 assessed by radiology. All the heads, treated with brilliant green, were cut in half to assess the degree of impregnation. On the X-ray image of head №1 the contrast agent has spread enough. In osteotomy, the impregnation with brilliant green head №2, №3, №4, №5 was seen in 3–4 mm around the needle passage place. Head №6 the bone was not impregnated. Despite the fact that the radiograph showed a sufficient spread of contrast agent, on the sections of the head, treated with brilliant green, showed the spread of liquid 3–4 mm around the needle passage place. This indicates that the impregnation of large bone is not effective

Background. External fixation is a method of osteosynthesis currently required in traumatology and orthopaedic surgery. Pin tract infection is a common problem in clinical practice. Infection occurs after a bacterial colonisation of the pin due to its contact with skin and local environment. To prevent such local contamination, one way to handle this issue is to create a specific coating using method which could be applied in the medical field. In this work we develop a surface coating for external fixator pins based on photocatalytic TiOα properties, producing a bactericidal effect with sufficient mechanical strength to be compatible with surgical use. Method. The morphology and structure of the sol-gel coating layers were characterised using, respectively, scanning electron microscopy and X-ray diffraction. Resistance properties of the coating were investigated by mechanical testing. Photo-degradation of acid orange 7 in aqueous solution was used as a probe, to assess the photo-catalytic activity of titanium dioxide layers under UV irradiation. The bactericidal effect induced by the process was evaluated against 2 strains: a Staphylococcus aureus and a multiresistant Staphylococcus epidermidis. Results. The coated pins showed good mechanical strength and efficient antibacterial effect after 1 hour of UV irradiation. Conclusion. Our study allowed to develop an antibacterial coating for stainless steel commonly used in surgical practice. The process using photoactive TiO2 exposed to UV irradiation is actually well known and applied in many disinfection fields, and exhibited efficiency against the two main bactericidal strains involved in pin tract infections. Mechanical tests confirmed the coating's ability to resist to important stresses. Moreover, this kind of coating created by sol-gel dip-coating techniques is not expensive and quite easy to do. As a consequence, we can hope that this new option would treat preventively pin tract infection, even if there is an important optimisation task to be done in order to amplify bactericidal properties. Level of evidence. II

Bone infection occurring after fractures or orthopedic surgery can progress to the chronic stage and lead to poor results of treatment. Optimal treatment of chronic osteomyelitis are stabilization the fracture, biological recovery of bone defects and destroy bacterial infection. Traditional methods of treatment are systemic administration of antibiotics and surgical treatment of active infection focus. Systemic antibiotics are part of the standard therapy after surgical treatment of infected bone, but their effectiveness is limited due to malnutrition and low absorption at the site of infection. Moreover, long-term treatment and higher doses are associated with serious side effects. The aim of this investigation was to study the results of the complex treatment of patients with chronic osteomyelitis using biodegradable nanomaterials “PerOssal” as antibiotic delivery system. The study was performed at Regional center traumatology and orthopedics, Karaganda, Kazakhstan. A total 20 patient with post-traumatic/post-operative osteomyelitis were included in this open-label, prospective study. Bacteriological examination was taken with the determination of culture and sensitivity test preoperatively, during and postoperatively. After radical surgical debridement and ultrasound cavitation, the bone cavity was full filled with Perosal which can be loaded with different antibiotics depending from the antibiotic sensitivity test. Postoperative wound is completely was sutured. Systemic antibiotic treatment are allowed. The course of infection was monitored by determination leukocyte count and blood sedimentation rate; blood samples were taken befor, 24 hours after surgery, and on days 3, 7, 10, 14. Wound healing was assessed on days 2, 3, 7, 10, and at the time of removal of sutures. Resorption of implanted beads and bone reconstruction were evaluated by X-ray at after operation and at approximately one, three and six months after implantation. A total of 20 patients (mean age 38,1 (26 to 53), 14 male, 6 female) were treated with Perossal pellets (AAP, Germany) from October 2013 to April 2015. Mean leukocyte counts and blood sedimentation rate were within the normal laboratory range and did not indicate infectious complications during the first 21 days after surgery. Primary wound healing occurred in 18 patients and secondary wound healing in two patients. There were two cases of re-infection during the course of the study, one of them related to an incomplete eradication of infected tissue and multidrug-resistant strain occurring during the course of the study, the other is occurred that patient non-compliance. Radiographic analysis six months after surgery showed progressive resorption of the implanted pellets, but only 10 cases have decreasing size of defects on X-ray. This study in adult patients with chronic post-traumatic/post-operative osteomyelitis demonstrated that these biodegradable bone filler pellets which can be loaded with different antibiotics are a clinically useful local antibiotic delivery system and bone substitute which can be used as an alternative to other anti-infective implants. The implantation of the pellets was safety and well tolerated in all patients. This composite can provide adequate protection against bacterial infection during the first weeks after implantation and to support the bone healing process

Objectives

Intramedullary fixation is considered the most stable treatment for pertrochanteric fractures of the proximal femur and cut-out is one of the most frequent mechanical complications. In order to determine the role of clinical variables and radiological parameters in predicting the risk of this complication, we analysed the data pertaining to a group of patients recruited over the course of six years.