Репозиторий Университета

Nearly half of patients with prostate cancer (PCa) harbour low- or intermediate-risk disease considered suitable for active surveillance (AS). However, up to 44% of patients discontinue AS within the first five years, highlighting the unmet clinical need for robust baseline risk-stratification tools that enable timely and accurate prediction of tumour progression. In this proof-of-concept study, we sought to investigate the added value of MRI-derived radiomic features to standard-of-care clinical parameters for improving baseline prediction of PCa progression in AS patients. Tumour T2-weighted imaging (T2WI) and apparent diffusion coefficient radiomic features were extracted, with rigorous calibration and pre-processing methods applied to select the most robust features for predictive modelling. Following leave-one-out cross-validation, the addition of T2WI-derived radiomic features to clinical variables alone improved the area under the ROC curve for predicting progression from 0.61 (95% confidence interval [CI] 0.481–0.743) to 0.75 (95% CI 0.64–0.86). These exploratory findings demonstrate the potential benefit of MRI-derived radiomics to add incremental benefit to clinical data only models in the baseline prediction of PCa progression on AS, paving the way for future multicentre studies validating the proposed model and evaluating its impact on clinical outcomes.

Viruses manipulate cellular metabolism and macromolecule recycling processes like autophagy. Dysregulated metabolism might lead to excessive inflammatory and autoimmune responses as observed in severe and long COVID-19 patients. Here we show that SARS-CoV-2 modulates cellular metabolism and reduces autophagy. Accordingly, compound-driven induction of autophagy limits SARS-CoV-2 propagation. In detail, SARS-CoV-2-infected cells show accumulation of key metabolites, activation of autophagy inhibitors (AKT1, SKP2) and reduction of proteins responsible for autophagy initiation (AMPK, TSC2, ULK1), membrane nucleation, and phagophore formation (BECN1, VPS34, ATG14), as well as autophagosome-lysosome fusion (BECN1, ATG14 oligomers). Consequently, phagophore-incorporated autophagy markers LC3B-II and P62 accumulate, which we confirm in a hamster model and lung samples of COVID-19 patients. Single-nucleus and single-cell sequencing of patient-derived lung and mucosal samples show differential transcriptional regulation of autophagy and immune genes depending on cell type, disease duration, and SARS-CoV-2 replication levels. Targeting of autophagic pathways by exogenous administration of the polyamines spermidine and spermine, the selective AKT1 inhibitor MK-2206, and the BECN1-stabilizing anthelmintic drug niclosamide inhibit SARS-CoV-2 propagation in vitro with IC50 values of 136.7, 7.67, 0.11, and 0.13 μM, respectively. Autophagy-inducing compounds reduce SARS-CoV-2 propagation in primary human lung cells and intestinal organoids emphasizing their potential as treatment options against COVID-19.

Adoptive cell therapy has received a great deal of interest in the treatment of advanced cancers that are resistant to traditional therapy. The tremendous success of chimeric antigen receptor (CAR)-engineered T (CAR-T) cells in the treatment of cancer, especially hematological cancers, has exposed CAR’s potential. However, the toxicity and significant limitations of CAR-T cell immunotherapy prompted research into other immune cells as potential candidates for CAR engineering. NK cells are a major component of the innate immune system, especially for tumor immunosurveillance. They have a higher propensity for immunotherapy in hematologic malignancies because they can detect and eliminate cancerous cells more effectively. In comparison to CAR-T cells, CAR-NK cells can be prepared from allogeneic donors and are safer with a lower chance of cytokine release syndrome and graft-versus-host disease, as well as being a more efficient antitumor activity with high efficiency for off-the-shelf production. Moreover, CAR-NK cells may be modified to target various antigens while also increasing their expansion and survival in vivo. Extensive preclinical research has shown that NK cells can be effectively engineered to express CARs with substantial cytotoxic activity against both hematological and solid tumors, establishing evidence for potential clinical trials of CAR-NK cells. In this review, we discuss recent advances in CAR-NK cell engineering in a variety of hematological malignancies, as well as the main challenges that influence the outcomes of CAR-NK cell-based tumor immunotherapies.

Underweight or overweight in adolescence is linked to several adverse health outcomes. Less evidence exists about the association between weight status and school-related psychosocial characteristics in high income countries. We sought to investigate the relationship between weight status and psychosomatic and school-related complaints with a focus on gender differences. The study is a cohort of 18,462 adolescents (12–19 years; 51% girls) conducted in Sweden. The associations between weight status and psychosomatic and school-related complaints were estimated by binary logistic regression adjusted for several potential confounders. After correction for multiple testing, being underweight or overweight/obese was adversely associated with several psychosomatic and school-related complaints with significant differences between boys and girls. Specifically, underweight boys had higher odds to have psychosomatic complaints than normal-weight boys, while no such associations were observed among underweight girls. Overweight/obese (vs. normal-weight) boys had higher odds to complain about headache, pain in the back/hips, and feeling low. Overweight/obese (vs. normal-weight) girls were more likely to complain about feeling low, anxious/worried and having difficulty in falling asleep (P ≤ 0.01). In relation to school-related complaints (e.g., being bullied at school and academic failure), greater associations were observed for overweight/obese girls and boys than for underweight adolescents compared with normal-weight peers.

Recently, mesenchymal stem/stromal cells (MSCs) due to their pro-angiogenic, anti-apoptotic, and immunoregulatory competencies along with fewer ethical issues are presented as a rational strategy for regenerative medicine. Current reports have signified that the pleiotropic effects of MSCs are not related to their differentiation potentials, but rather are exerted through the release of soluble paracrine molecules. Being nano-sized, non-toxic, biocompatible, barely immunogenic, and owning targeting capability and organotropism, exosomes are considered nanocarriers for their possible use in diagnosis and therapy. Exosomes convey functional molecules such as long non-coding RNAs (lncRNAs) and micro-RNAs (miRNAs), proteins (e.g., chemokine and cytokine), and lipids from MSCs to the target cells. They participate in intercellular interaction procedures and enable the repair of damaged or diseased tissues and organs. Findings have evidenced that exosomes alone are liable for the beneficial influences of MSCs in a myriad of experimental models, suggesting that MSC- exosomes can be utilized to establish a novel cell-free therapeutic strategy for the treatment of varied human disorders, encompassing myocardial infarction (MI), CNS-related disorders, musculoskeletal disorders (e.g. arthritis), kidney diseases, liver diseases, lung diseases, as well as cutaneous wounds. Importantly, compared with MSCs, MSC- exosomes serve more steady entities and reduced safety risks concerning the injection of live cells, such as microvasculature occlusion risk. In the current review, we will discuss the therapeutic potential of MSC- exosomes as an innovative approach in the context of regenerative medicine and highlight the recent knowledge on MSC- exosomes in translational medicine, focusing on in vivo researches.

Introduction: The claustrum is a structure involved in formation of several cortical and subcortical neural microcircuits which may be involved in such functions as conscious sensations and rewarding behavior. The claustrum is regarded as a multi-modal information processing network. Pathology of the claustrum is seen in certain neurological disorders. To date, there are not enough comprehensive studies that contain accurate information regarding involvement of the claustrum in development of neurological disorders. Objective: Our review aims to provide an update on claustrum anatomy, ontogenesis, cytoarchitecture, neural networks and their functional relation to the incidence of neurological diseases. Materials and methods: A literature review was conducted using the Google Scholar, PubMed, NCBI MedLine, and eLibrary databases. Results: Despite new methods that have made it possible to study the claustrum at the molecular, genetic and epigenetic levels, its functions and connectivity are still poorly understood. The anatomical location, relatively uniform cytoarchitecture, and vast network of connections suggest a divergent role of the claustrum in integration and processing of input information and formation of coherent perceptions. Several studies have shown changes in the appearance, structure and volume of the claustrum in neurodegenerative diseases, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), autism, schizophrenia, and depressive disorders. Taking into account the structure, ontogenesis, and functions of the claustrum, this literature review offers insight into understanding the crucial role of this structure in brain function and behavior.

Prokineticin-2 (Prok2) is an important secreted protein likely involved in the pathogenesis of several acute and chronic neurological diseases through currently unidentified regulatory mechanisms. The initial mechanical injury of neurons by traumatic brain injury triggers multiple secondary responses including various cell death programs. One of these is ferroptosis, which is associated with dysregulation of iron and thiols and culminates in fatal lipid peroxidation. Here, we explore the regulatory role of Prok2 in neuronal ferroptosis in vitro and in vivo. We show that Prok2 prevents neuronal cell death by suppressing the biosynthesis of lipid peroxidation substrates, arachidonic acid-phospholipids, via accelerated F-box only protein 10 (Fbxo10)-driven ubiquitination, degradation of long-chain-fatty-acid-CoA ligase 4 (Acsl4), and inhibition of lipid peroxidation. Mice injected with adeno-associated virus-Prok2 before controlled cortical impact injury show reduced neuronal degeneration and improved motor and cognitive functions, which could be inhibited by Fbxo10 knockdown. Our study shows that Prok2 mediates neuronal cell deaths in traumatic brain injury via ferroptosis.

Recently, mesenchymal stem/stromal cells (MSCs) due to their pro-angiogenic, anti-apoptotic, and immunoregulatory competencies along with fewer ethical issues are presented as a rational strategy for regenerative medicine. Current reports have signified that the pleiotropic effects of MSCs are not related to their differentiation potentials, but rather are exerted through the release of soluble paracrine molecules. Being nano-sized, non-toxic, biocompatible, barely immunogenic, and owning targeting capability and organotropism, exosomes are considered nanocarriers for their possible use in diagnosis and therapy. Exosomes convey functional molecules such as long non-coding RNAs (lncRNAs) and micro-RNAs (miRNAs), proteins (e.g., chemokine and cytokine), and lipids from MSCs to the target cells. They participate in intercellular interaction procedures and enable the repair of damaged or diseased tissues and organs. Findings have evidenced that exosomes alone are liable for the beneficial influences of MSCs in a myriad of experimental models, suggesting that MSC- exosomes can be utilized to establish a novel cell-free therapeutic strategy for the treatment of varied human disorders, encompassing myocardial infarction (MI), CNS-related disorders, musculoskeletal disorders (e.g. arthritis), kidney diseases, liver diseases, lung diseases, as well as cutaneous wounds. Importantly, compared with MSCs, MSC- exosomes serve more steady entities and reduced safety risks concerning the injection of live cells, such as microvasculature occlusion risk. In the current review, we will discuss the therapeutic potential of MSC- exosomes as an innovative approach in the context of regenerative medicine and highlight the recent knowledge on MSC- exosomes in translational medicine, focusing on in vivo researches.

Introduction: The claustrum is a structure involved in formation of several cortical and subcortical neural microcircuits which may be involved in such functions as conscious sensations and rewarding behavior. The claustrum is regarded as a multi-modal information processing network. Pathology of the claustrum is seen in certain neurological disorders. To date, there are not enough comprehensive studies that contain accurate information regarding involvement of the claustrum in development of neurological disorders. Objective: Our review aims to provide an update on claustrum anatomy, ontogenesis, cytoarchitecture, neural networks and their functional relation to the incidence of neurological diseases. Materials and methods: A literature review was conducted using the Google Scholar, PubMed, NCBI MedLine, and eLibrary databases. Results: Despite new methods that have made it possible to study the claustrum at the molecular, genetic and epigenetic levels, its functions and connectivity are still poorly understood. The anatomical location, relatively uniform cytoarchitecture, and vast network of connections suggest a divergent role of the claustrum in integration and processing of input information and formation of coherent perceptions. Several studies have shown changes in the appearance, structure and volume of the claustrum in neurodegenerative diseases, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), autism, schizophrenia, and depressive disorders. Taking into account the structure, ontogenesis, and functions of the claustrum, this literature review offers insight into understanding the crucial role of this structure in brain function and behavior.

Prokineticin-2 (Prok2) is an important secreted protein likely involved in the pathogenesis of several acute and chronic neurological diseases through currently unidentified regulatory mechanisms. The initial mechanical injury of neurons by traumatic brain injury triggers multiple secondary responses including various cell death programs. One of these is ferroptosis, which is associated with dysregulation of iron and thiols and culminates in fatal lipid peroxidation. Here, we explore the regulatory role of Prok2 in neuronal ferroptosis in vitro and in vivo. We show that Prok2 prevents neuronal cell death by suppressing the biosynthesis of lipid peroxidation substrates, arachidonic acid-phospholipids, via accelerated F-box only protein 10 (Fbxo10)-driven ubiquitination, degradation of long-chain-fatty-acid-CoA ligase 4 (Acsl4), and inhibition of lipid peroxidation. Mice injected with adeno-associated virus-Prok2 before controlled cortical impact injury show reduced neuronal degeneration and improved motor and cognitive functions, which could be inhibited by Fbxo10 knockdown. Our study shows that Prok2 mediates neuronal cell deaths in traumatic brain injury via ferroptosis.

Background: During the last decades, the abuse of anabolic androgenic steroids (AASs) has become popular among professional and recreational athletes. The abuse of AASs leads to decreased levels of sex hormones, but the available literature a gives very small pool of data regarding the effects of swimming alone or combined with AASs on testicle tissue. The aim of this study was to investigate the effects of four-week administration of nandrolone decanoate and swimming training alone or in combination on morphometric parameters, androgen receptor (AR) and redox state in testicle tissue. The study included Wistar albino male rats, 10 weeks old, classified into 4 groups: control (T-N-), nandrolone (T-N+), swimming training (T+N-) and swimming training with nandrolone (T+N+). The rats from nandrolone (N+) groups received nandrolone decanoate 20 mg/kg b.w.once per week. The rats from training (T+) groups, swam 1 h/day 5 days/week. The isolated testicles were measured, left testicles were routinely processed for histological analysis, while right testicles were homogenized and prepared for the analysis of the following oxidative stress biomarkers: index of lipid peroxidation (TBARS), nitrites, catalase, superoxide dismutase (SOD), and reduced glutathione (GSH). Results: Diameter, as well as cross-section area of seminiferous tubules were decreased by 10 % and 21 % (respectively) in the T-N+ group and by 15% and 41 % (respectively) in the T+N+ group compared to control. Interstitium of the testicles was decreased in all experimental groups. Reduction of immunoreactivity of AR in T-N+ group was 22 %, in T+N+ group was 9 % compared to control. TBARS levels were increased in T+N- and T+N+ groups. Nitrites were decreased in T+N+ group. Catalase activity was increased in all experimental groups. Swimming alone or combined with nandrolone decreased the level of GSH compared to control. SOD activity was decreased in T-N+ and T+N+ groups compared to control. Conclusions: Nandrolone alone or combined with swimming decreased morphometric parameters and amount of AR in testicle tissue. Changes in the redox state indicate reproductive dysfunction.

Background: During the last decades, the abuse of anabolic androgenic steroids (AASs) has become popular among professional and recreational athletes. The abuse of AASs leads to decreased levels of sex hormones, but the available literature a gives very small pool of data regarding the effects of swimming alone or combined with AASs on testicle tissue. The aim of this study was to investigate the effects of four-week administration of nandrolone decanoate and swimming training alone or in combination on morphometric parameters, androgen receptor (AR) and redox state in testicle tissue. The study included Wistar albino male rats, 10 weeks old, classified into 4 groups: control (T-N-), nandrolone (T-N+), swimming training (T+N-) and swimming training with nandrolone (T+N+). The rats from nandrolone (N+) groups received nandrolone decanoate 20 mg/kg b.w.once per week. The rats from training (T+) groups, swam 1 h/day 5 days/week. The isolated testicles were measured, left testicles were routinely processed for histological analysis, while right testicles were homogenized and prepared for the analysis of the following oxidative stress biomarkers: index of lipid peroxidation (TBARS), nitrites, catalase, superoxide dismutase (SOD), and reduced glutathione (GSH). Results: Diameter, as well as cross-section area of seminiferous tubules were decreased by 10 % and 21 % (respectively) in the T-N+ group and by 15% and 41 % (respectively) in the T+N+ group compared to control. Interstitium of the testicles was decreased in all experimental groups. Reduction of immunoreactivity of AR in T-N+ group was 22 %, in T+N+ group was 9 % compared to control. TBARS levels were increased in T+N- and T+N+ groups. Nitrites were decreased in T+N+ group. Catalase activity was increased in all experimental groups. Swimming alone or combined with nandrolone decreased the level of GSH compared to control. SOD activity was decreased in T-N+ and T+N+ groups compared to control. Conclusions: Nandrolone alone or combined with swimming decreased morphometric parameters and amount of AR in testicle tissue. Changes in the redox state indicate reproductive dysfunction.

Background: New treatments are currently offering new opportunities and challenges in clinical management and research in the migraine field. There is the need of homogenous criteria to identify candidates for treatment escalation as well as of reliable criteria to identify refractoriness to treatment. To overcome those issues, the European Headache Federation (EHF) issued a Consensus document to propose criteria to approach difficult-to-treat migraine patients in a standardized way. The Consensus proposed well-defined criteria for resistant migraine (i.e., patients who do not respond to some treatment but who have residual therapeutic opportunities) and refractory migraine (i.e., patients who still have debilitating migraine despite maximal treatment efforts). The aim of this study was to better understand the perceived impact of resistant and refractory migraine and the attitude of physicians involved in migraine care toward those conditions. Methods: We conducted a web-questionnaire-based cross-sectional international study involving physicians with interest in headache care. Results: There were 277 questionnaires available for analysis. A relevant proportion of participants reported that patients with resistant and refractory migraine were frequently seen in their clinical practice (49.5% for resistant and 28.9% for refractory migraine); percentages were higher when considering only those working in specialized headache centers (75% and 46% respectively). However, many physicians reported low or moderate confidence in managing resistant (8.1% and 43.3%, respectively) and refractory (20.7% and 48.4%, respectively) migraine patients; confidence in treating resistant and refractory migraine patients was different according to the level of care and to the number of patients visited per week. Patients with resistant and refractory migraine were infrequently referred to more specialized centers (12% and 19%, respectively); also in this case, figures were different according to the level of care. Conclusions: This report highlights the clinical relevance of difficult-to-treat migraine and the presence of unmet needs in this field. There is the need of more evidence regarding the management of those patients and clear guidance referring to the organization of care and available opportunities.

In countries where headache services exist at all, their focus is usually on specialist (tertiary) care. This is clinically and economically inappropriate: most headache disorders can effectively and more efficiently (and at lower cost) be treated in educationally supported primary care. At the same time, compartmentalizing divisions between primary, secondary and tertiary care in many health-care systems create multiple inefficiencies, confronting patients attempting to navigate these levels (the “patient journey”) with perplexing obstacles. High demand for headache care, estimated here in a needs-assessment exercise, is the biggest of the challenges to reform. It is also the principal reason why reform is necessary. The structured headache services model presented here by experts from all world regions on behalf of the Global Campaign against Headache is the suggested health-care solution to headache. It develops and refines previous proposals, responding to the challenge of high demand by basing headache services in primary care, with two supporting arguments. First, only primary care can deliver headache services equitably to the large numbers of people needing it. Second, with educational supports, they can do so effectively to most of these people. The model calls for vertical integration between care levels (primary, secondary and tertiary), and protection of the more advanced levels for the minority of patients who need them. At the same time, it is amenable to horizontal integration with other care services. It is adaptable according to the broader national or regional health services in which headache services should be embedded. It is, according to evidence and argument presented, an efficient and cost-effective model, but these are claims to be tested in formal economic analyses.

The purpose of this study was to characterize the morphological variations in the proximal attachments and create an accurate classification of the PPM for use in planning surgical procedures in this area, for evaluating radiological imaging and rehabilitation. One hundred and thirty-four lower limbs of body donors (52 woman and 82 man) fixed in 10% formalin solution were examined. The popliteus muscle was present in all 134 limbs. Four main types were identified with subtypes. The most common type was Type I (34.3%), characterized by a single tendon in the popliteus sulcus. Type II (30.6%) characterized by a main tendon in the popliteus sulcus and accessory bands. This type was divided into five subtypes (A–E) based on presence of specific accessory bands. Type III (15.3%) was characterized by two tendons in the popliteal sulcus. Type IV (19.4%) was characterized by two tendons in the popliteus sulcus and additional bands. This type was also divided into five subtypes (A–E) based on presence of specific accessory bands. The popliteofibular ligament was present in 90.3% of cases. A new classification based on a proximal attachment is proposed. The popliteus tendon is characterized by a very high morphological variability, which can affect posterolateral knee stability and the natural rotation of the tibia. Such a classification system may be useful for clinicians performing medical procedures within the knee joint, including orthopedic surgeons.

Alcohol consumption is a major risk factor for premature mortality. Although alcohol control policies are known to impact all-cause mortality rates, the effect that policies have on specific age groups is an important area of research. This study investigates the effect of alcohol control policies implemented in 2009 and 2017 in Lithuania on all-cause mortality rates. All-cause mortality rates (deaths per 100,000 people) were obtained for 2001–2018 by 10-year age groups (20–29, 30–39, 40–49 years, etc.). All-cause mortality rates, independent of macro-level secular trends (e.g., economic trends) were examined. Following a joinpoint analysis to control for secular trends, an interrupted time series analysis showed that alcohol control policies had a significant effect on all-cause mortality rates (p =.018), with the most significant impact occurring among young adults (20–29 and 30–39 years of age). For these age groups, their mortality rate decreased during the 12 months following policy implementation (following the policy in 2009 for those 20–29 years of age, p =.0026, and following the policy in 2017 for those 30–39 years of age, p =.011). The results indicate that alcohol control policy can impact all-cause mortality rates, above and beyond secular trends, and that the impact is significant among young adults.

The purpose of this study was to characterize the morphological variations in the proximal attachments and create an accurate classification of the PPM for use in planning surgical procedures in this area, for evaluating radiological imaging and rehabilitation. One hundred and thirty-four lower limbs of body donors (52 woman and 82 man) fixed in 10% formalin solution were examined. The popliteus muscle was present in all 134 limbs. Four main types were identified with subtypes. The most common type was Type I (34.3%), characterized by a single tendon in the popliteus sulcus. Type II (30.6%) characterized by a main tendon in the popliteus sulcus and accessory bands. This type was divided into five subtypes (A–E) based on presence of specific accessory bands. Type III (15.3%) was characterized by two tendons in the popliteal sulcus. Type IV (19.4%) was characterized by two tendons in the popliteus sulcus and additional bands. This type was also divided into five subtypes (A–E) based on presence of specific accessory bands. The popliteofibular ligament was present in 90.3% of cases. A new classification based on a proximal attachment is proposed. The popliteus tendon is characterized by a very high morphological variability, which can affect posterolateral knee stability and the natural rotation of the tibia. Such a classification system may be useful for clinicians performing medical procedures within the knee joint, including orthopedic surgeons.

Alcohol consumption is a major risk factor for premature mortality. Although alcohol control policies are known to impact all-cause mortality rates, the effect that policies have on specific age groups is an important area of research. This study investigates the effect of alcohol control policies implemented in 2009 and 2017 in Lithuania on all-cause mortality rates. All-cause mortality rates (deaths per 100,000 people) were obtained for 2001–2018 by 10-year age groups (20–29, 30–39, 40–49 years, etc.). All-cause mortality rates, independent of macro-level secular trends (e.g., economic trends) were examined. Following a joinpoint analysis to control for secular trends, an interrupted time series analysis showed that alcohol control policies had a significant effect on all-cause mortality rates (p =.018), with the most significant impact occurring among young adults (20–29 and 30–39 years of age). For these age groups, their mortality rate decreased during the 12 months following policy implementation (following the policy in 2009 for those 20–29 years of age, p =.0026, and following the policy in 2017 for those 30–39 years of age, p =.011). The results indicate that alcohol control policy can impact all-cause mortality rates, above and beyond secular trends, and that the impact is significant among young adults.

The purpose of this study was to characterize the morphological variations in the proximal attachments and create an accurate classification of the PPM for use in planning surgical procedures in this area, for evaluating radiological imaging and rehabilitation. One hundred and thirty-four lower limbs of body donors (52 woman and 82 man) fixed in 10% formalin solution were examined. The popliteus muscle was present in all 134 limbs. Four main types were identified with subtypes. The most common type was Type I (34.3%), characterized by a single tendon in the popliteus sulcus. Type II (30.6%) characterized by a main tendon in the popliteus sulcus and accessory bands. This type was divided into five subtypes (A–E) based on presence of specific accessory bands. Type III (15.3%) was characterized by two tendons in the popliteal sulcus. Type IV (19.4%) was characterized by two tendons in the popliteus sulcus and additional bands. This type was also divided into five subtypes (A–E) based on presence of specific accessory bands. The popliteofibular ligament was present in 90.3% of cases. A new classification based on a proximal attachment is proposed. The popliteus tendon is characterized by a very high morphological variability, which can affect posterolateral knee stability and the natural rotation of the tibia. Such a classification system may be useful for clinicians performing medical procedures within the knee joint, including orthopedic surgeons.