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Soft Tissue Scaffolds in Breast Reconstruction: Evolution from Acellular Dermal Matrices to Synthetic Polymers -
Preclinical Rheumatoid Arthritis: Pathogenesis, Risk Stratification, and Therapeutic Interception -
Cardiac Involvement in Emery–Dreifuss Muscular Dystrophy, from Arrhythmias to Heart Failure and Sudden Death: A Contemporary Review -
Adherence to CPAP in Randomized Controlled Trials in Obstructive Sleep Apnoea—A Meta-Analysis and Investigation of Predictors -
Navigating the Hemostatic Balance: Anticoagulation and Antiplatelet Therapy in Patients with Thrombocytopenia
Journal Description
Journal of Clinical Medicine
Journal of Clinical Medicine
is an international, peer-reviewed, open access journal of clinical medicine, published semimonthly online by MDPI. The International Bone Research Association (IBRA), Spanish Society of Hematology and Hemotherapy (SEHH), Japan Association for Clinical Engineers (JACE), European Independent Foundation in Angiology/ Vascular Medicine (VAS) and others are all affiliated with JCM, and their members receive a discount on article processing charges.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, Embase, CAPlus / SciFinder, and other databases.
- Journal Rank: JCR - Q1 (Medicine, General and Internal) / CiteScore - Q1 (General Medicine)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 18.5 days after submission; acceptance to publication is undertaken in 2.7 days (median values for papers published in this journal in the second half of 2025).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
- Companion journals for JCM include: Epidemiologia, Transplantology, Uro, Sinusitis, Rheumato, Journal of Clinical & Translational Ophthalmology, Journal of Vascular Diseases, Osteology, Complications, Therapeutics, Sclerosis, Pharmacoepidemiology, Journal of CardioRenal Medicine and Rare Diseases and Therapeutics.
- Journal Clusters of Hematology: Hemato, Hematology Reports, Thalassemia Reports and Journal of Clinical Medicine.
Impact Factor:
2.9 (2024);
5-Year Impact Factor:
3.3 (2024)
Latest Articles
Osteotomy as an Intraoperative Determinant of Early Postoperative Outcomes After Mandibular Third Molar Extraction: A Secondary Analysis of a Randomized Clinical Trial
J. Clin. Med. 2026, 15(10), 3756; https://doi.org/10.3390/jcm15103756 - 13 May 2026
Abstract
Background/Objectives: Surgical extraction of impacted mandibular third molars is frequently associated with postoperative morbidity, including swelling, trismus, and pain. However, the extent to which osteotomy contributes to these outcomes remains unclear. The aim of this study was to evaluate osteotomy as an intraoperative
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Background/Objectives: Surgical extraction of impacted mandibular third molars is frequently associated with postoperative morbidity, including swelling, trismus, and pain. However, the extent to which osteotomy contributes to these outcomes remains unclear. The aim of this study was to evaluate osteotomy as an intraoperative determinant of early postoperative morbidity following mandibular third molar extraction. Methods: This study represents a secondary analysis of data obtained from a randomized clinical trial. Patients undergoing surgical removal of impacted mandibular third molars were categorized according to whether osteotomy was required during the procedure. Postoperative outcomes included surgical duration, facial swelling (primary outcome) assessed by linear facial measurements, maximal mouth opening (trismus), postoperative pain intensity, and early soft tissue healing evaluated using the Early Healing Index. Results: Procedures involving osteotomy were associated with significantly longer surgical duration, as well as greater postoperative swelling and trismus during the early postoperative period. The most pronounced difference in swelling was observed along facial measurement line A on postoperative day 3. Multivariable analysis confirmed that osteotomy remained independently associated with increased postoperative swelling and trismus after adjustment for age, sex, and the original six-arm treatment allocation. In contrast, no statistically significant differences were found between the groups in postoperative pain intensity or early soft tissue healing. Conclusions: Osteotomy during mandibular third molar extraction is independently associated with increased early postoperative morbidity, particularly in terms of swelling and trismus. However, bone removal does not appear to negatively affect early soft tissue healing of the surgical site.
Full article
(This article belongs to the Special Issue Clinical Updates on Oral Health and Dental Care)
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Open AccessArticle
Impact of Statin Therapy on Clinical Outcomes of Patients Hospitalised with Skin and Soft Tissue Infections
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Ying Chuin Wee, Udul Hewage, Chris Horwood and Yogesh Sharma
J. Clin. Med. 2026, 15(10), 3755; https://doi.org/10.3390/jcm15103755 - 13 May 2026
Abstract
Background: Statins have anti-inflammatory properties beyond their lipid-lowering effects, but their impact on skin and soft tissue infections (SSTIs) remains unclear. This study evaluated whether statins improve clinical outcomes in patients hospitalised with SSTIs. Methods: Adults aged ≥18 years hospitalised with
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Background: Statins have anti-inflammatory properties beyond their lipid-lowering effects, but their impact on skin and soft tissue infections (SSTIs) remains unclear. This study evaluated whether statins improve clinical outcomes in patients hospitalised with SSTIs. Methods: Adults aged ≥18 years hospitalised with SSTIs at a tertiary hospital in Australia between 1 June 2021 and 31 December 2021 were identified using the International Classification of Diseases 10th Revision Australian Modification (ICD-10-AM) codes. Patients were categorised into two groups based on statin use at admission. Multivariable regression models assessed differences in clinical outcomes including length of hospital stay (LOS), septic shock, Medical Emergency Response Team (MET) calls, intensive care unit (ICU) admission, mortality and 30-day readmissions, adjusting for age, sex, Charlson Comorbidity Index and C-reactive protein levels. Results: Of 387 admissions, complete data were available for 381 patients. The mean (standard deviation [SD]) age was 58.5 years (21.9 years), and 55.9% were male. Statins were used by 110 patients (28.9%) at admission. Statin users were older, had more comorbidities, and were more likely to have positive culture results than statin non-users (p < 0.05). Median (interquartile range [IQR]) LOS was significantly longer for statin users compared to non-users (4 [2,7] versus 3 [2,5] days, p < 0.05). However, after adjusted analysis, LOS was not significantly different between the two groups (adjusted incidence risk ratio [aIRR] 1.08; 95% confidence interval [CI] 0.97–1.20, p = 0.134). Other clinical outcomes were also similar between the two groups. Conclusions: This study found that statin use at admission was not associated with statistically significant differences in clinical outcomes among patients hospitalised with SSTIs.
Full article
Open AccessArticle
Association Between Diabetic Foot Lesions and Diabetic Foot Ulcers: A Cross-Sectional Study
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Moe Murai, Yoshitaka Hashimoto, Haruka Utsuyama, Takashi Ogasawara, Akifumi Shiota, Nozomi Yoshioka, Yusuke Hamazawa and Michiaki Fukui
J. Clin. Med. 2026, 15(10), 3754; https://doi.org/10.3390/jcm15103754 - 13 May 2026
Abstract
Aims: The purpose of this study was to clarify the prevalence of diabetic foot lesions and their association with lower-limb amputations and/or foot ulcers. Materials and Methods: In this cross-sectional study, 968 patients with diabetes were surveyed. Diabetic foot lesions were defined according
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Aims: The purpose of this study was to clarify the prevalence of diabetic foot lesions and their association with lower-limb amputations and/or foot ulcers. Materials and Methods: In this cross-sectional study, 968 patients with diabetes were surveyed. Diabetic foot lesions were defined according to the broad national criteria, which encompass both mild abnormalities and more advanced conditions. Based on this definition, foot lesions were assessed using a questionnaire comprising the following 10 items: a history of lower-limb amputations, a history of treatment of foot lesions, numbness/loss of sensation/pain, skin discolorations, skin symptoms, nail abnormalities, foot ulcers/gangrene, foot deformities, foot infection, and intermittent claudication. Logistic regression analysis was used to examine risk factors for foot lesions. Area under the curve (AUC) of the number of foot lesions for lower-limb amputations or foot ulcers/gangrene was calculated using the receiver operating characteristic curve (ROC) analysis. Results: Approximately two-thirds of the patients had at least one type of diabetic foot lesion. Logistic regression analysis revealed that women, past or current smoking, a history of cardiovascular disease, and nephropathy were associated with the risk of diabetic foot lesions. According to the ROC analysis, the optimal cut-off point of number of diabetic foot lesions was three for identifying patients with a history of lower-limb amputation and/or the presence of foot ulcers or gangrene (AUC 0.80 (95% CI, 0.70–0.91), p < 0.01). Conclusions: Diabetic foot lesions are common in patients with diabetes and the prevalence of diabetic foot lesions was higher in patients with a history of lower-limb amputations and/or the presence of foot ulcers or gangrene. Early detection and care of diabetic foot lesions are necessary to prevent lower-limb amputations and foot ulcers.
Full article
(This article belongs to the Special Issue Diabetic Foot: From Prevention to Diagnosis and Treatment)
Open AccessReview
From Invisible to Visible: Cutting-Edge Ultrasound Insights into Entheses of the Distal Extremities in Rheumatology
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Luis Coronel, Chiara Rizzo, Juan José de Agustin, David Bong, Maribel Miguel-Pérez, Stefano Alivernini, Lene Terslev, Maria Antonietta D’Agostino and Ingrid Möller
J. Clin. Med. 2026, 15(10), 3753; https://doi.org/10.3390/jcm15103753 - 13 May 2026
Abstract
Musculoskeletal ultrasound (MSUS) is a well-established and reliable tool for the evaluation of entheses and enthesitis, particularly at larger and accessible sites. Recent technological advances, including high- and ultra-high-frequency transducers, have expanded its potential, enabling detailed assessment of distal extremity entheses. This narrative
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Musculoskeletal ultrasound (MSUS) is a well-established and reliable tool for the evaluation of entheses and enthesitis, particularly at larger and accessible sites. Recent technological advances, including high- and ultra-high-frequency transducers, have expanded its potential, enabling detailed assessment of distal extremity entheses. This narrative review provides a focused and updated perspective on this evolving field, highlighting three key advances. First, the identification and characterization of previously underrecognized entheseal sites in the distal extremities, such as pulley systems, retinacula, novel tendon insertions, and collateral ligaments, broadening the morphological spectrum of entheseal imaging. This is complemented by improved evaluation of vascularization through microvascular imaging and contrast-enhanced US (CEUS). Second, the emergence of interventional approaches, particularly US-guided entheseal biopsy, offers a novel means to investigate entheseal tissue in vivo and may establish a link between imaging and histopathology. Third, the integration of advanced functional imaging modalities, including elastography and multispectral optoacoustic tomography (MSOT), provides preliminary additional insights into the biomechanical and molecular properties of the enthesis beyond conventional structural assessment. Collectively, these developments support new investigational perspectives, positioning MSUS as a dynamic and integrative modality capable of exploring new anatomical territories and biological dimensions, with the potential to reshape the understanding and evaluation of entheseal involvement in rheumatology.
Full article
(This article belongs to the Special Issue Clinical Updates in Imaging of Musculoskeletal Diseases)
Open AccessArticle
Multidisciplinary Decision-Making and Integrated Strategies in Stage III Non-Small Cell Lung Cancer: Exploring Clinical Reasoning in Therapeutic Choices
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Paolo Borghetti, Fabiana Vitiello, Niccolò Giaj-Levra, Alessio Bruni, Fabiana Cecere, Marco Chiappetta, Patrizia Ciammella, Francesco Guerrera, Antonio Mazzella, Michele Montrone, Alessandro Russo, Vieri Scotti, Diego Signorelli, Stefano Vagge and Filippo Lococo
J. Clin. Med. 2026, 15(10), 3752; https://doi.org/10.3390/jcm15103752 - 13 May 2026
Abstract
Background/Objectives: Stage III non-small cell lung cancer (NSCLC) is a heterogeneous and clinically challenging disease. Despite therapeutic advances, decisions regarding resectability and treatment sequencing remain complex. Multidisciplinary discussion (MDD) is increasingly recognized as key to personalized, evidence-based care. Methods: The “Integrate
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Background/Objectives: Stage III non-small cell lung cancer (NSCLC) is a heterogeneous and clinically challenging disease. Despite therapeutic advances, decisions regarding resectability and treatment sequencing remain complex. Multidisciplinary discussion (MDD) is increasingly recognized as key to personalized, evidence-based care. Methods: The “Integrate 6.0” conference gathered approximately 90 lung cancer specialists, including oncologists, thoracic surgeons, and radiation oncologists, divided into mixed groups simulating multidisciplinary team (MDT) meetings. Groups reviewed complex clinical cases, supported by facilitators providing concise, evidence-based updates. A pre-event survey explored MDT structure and dynamics across institutions. Results: The survey highlighted considerable variability in MDT composition and practices. Most participants had significant involvement in thoracic oncology. Discussions revealed higher consensus in straightforward cases, while complex stage III scenarios—especially with driver mutations or bulky nodal disease—required more nuanced, collaborative decision making. Key topics included neoadjuvant chemoimmunotherapy, surgery in borderline resectable cases, and managing immune-related toxicities. Conclusions: “Integrate 6.0” effectively connected theoretical knowledge with real-world practice through interactive, multidisciplinary dialogue. It underscored the vital role of MDD in managing complex stage III NSCLC and the need for adaptable treatment strategies. Future conferences should assess MDD’s impact on outcomes and expand participation to include molecular pathologists and geriatricians.
Full article
(This article belongs to the Special Issue Non-Small Cell Lung Cancer (NSCLC): Recent Advances in Clinical Diagnosis and Treatment)
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Bidirectional Associations Between Blood Glucose and Blood Pressure: A Data-Driven Causal Analysis Using Structural Equation Modelling and Granger Causality on NHANES Longitudinal Data
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Irina Naskinova, Mikhail Kolev, Mariyan Milev, Hristo Kalinov, Meglena Lazarova, Stanislava Stoilova and Iveta Nikolova
J. Clin. Med. 2026, 15(10), 3751; https://doi.org/10.3390/jcm15103751 - 13 May 2026
Abstract
Background and Objectives: Whether hyperglycaemia causes hypertension, hypertension worsens glycaemic control, or both conditions arise from shared metabolic drivers remains clinically consequential yet unresolved. This study applies a triangulated causal inference framework to large-scale population data to quantify the direction, magnitude, and robustness
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Background and Objectives: Whether hyperglycaemia causes hypertension, hypertension worsens glycaemic control, or both conditions arise from shared metabolic drivers remains clinically consequential yet unresolved. This study applies a triangulated causal inference framework to large-scale population data to quantify the direction, magnitude, and robustness of the glucose–blood pressure relationship. The primary objective is to test for bidirectional causal effects between glycaemic status and blood pressure; secondary objectives include quantifying effect magnitudes by multiple complementary methods and assessing robustness to unmeasured confounding. Materials and Methods: We analysed 55,386 adults from the National Health and Nutrition Examination Survey (NHANES, 1999–2023). Multiple causal inference techniques were integrated: directed acyclic graph (DAG) testing, structural equation modelling (SEM) with latent constructs, propensity score matching (PSM), inverse probability weighting (IPW), doubly robust augmented IPW (AIPW), and E-value/Rosenbaum Γ sensitivity analyses, with external replication in the Framingham Heart Study data (n = 4240). Results: All of the methods used confirmed the bidirectional effects. PSM showed that hyperglycaemia increased systolic BP by 1.76 mmHg (95% CI: 0.58–2.96, p = 0.005), and hypertension increased fasting glucose by 6.55 mg/dL (95% CI: 4.61–8.58, p < 0.001), revealing a marked asymmetry favouring the BP → glucose direction. AIPW confirmed both effects (3.51 mmHg and 6.15 mg/dL, both p < 0.001). SEM identified significant bidirectional structural paths between latent glycaemic and blood-pressure constructs, with the Glycaemic → BPState path showing a negative coefficient (β = −0.15, p = 0.043), a sign reversal attributable to conditioning on the shared latent metabolic-syndrome factor. Sensitivity analyses indicated that an unmeasured confounder would need associations of RR ≥ 1.40–1.64 with both exposure and outcome to nullify these estimates, representing moderate robustness. Conclusions: The BP → glucose pathway is the dominant causal direction, suggesting that prioritisation of hypertension control may yield underappreciated benefits for glycaemic regulation. These findings support integrated cardiometabolic management strategies.
Full article
(This article belongs to the Special Issue Clinical Advances in Diabetes, Obesity, and Hypertension)
Open AccessArticle
FOOPAS Study: Functional Assessment and Prognostic Value in Aortic Valve Replacement for Patients ≥ 75 Years
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Dennis Eckner, Susanne Wicklein, Markus Gosch, Theodor Fischlein, Basel Habboub, Jürgen Jessl, Matthias Pauschinger and Ferdinand Vogt
J. Clin. Med. 2026, 15(10), 3750; https://doi.org/10.3390/jcm15103750 - 13 May 2026
Abstract
Background: Because of demographic changes, the number of older patients undergoing cardiac interventions has increased. The most common indication in this group is aortic valve stenosis, treated with either surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVR), with good
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Background: Because of demographic changes, the number of older patients undergoing cardiac interventions has increased. The most common indication in this group is aortic valve stenosis, treated with either surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVR), with good outcomes. Our study investigated whether the heart team’s choice of intervention (TAVI, SAVR, or conservative) is influenced by geriatric assessment results. Methods: This study was a single-centre, prospective, longitudinal case–control study conducted over 12 months and did not affect routine diagnostic examinations or clinical decisions. After risk stratification and clinical evaluation, patients were assigned to undergo TAVI, SAVR, or conservative management. Cardiological evaluation and geriatric assessment were performed for up to 12 months. Results: Of 135 patients (mean age 81 ± 4.6 years), 60% underwent TAVI, 29% SAVR, and 11% conservative therapy. Age, Frailty Score, cognition, and nutritional status were significantly associated with the heart team’s decision, whereas EuroSCORE II remained the only independent predictor of one-year mortality (OR 1.58, 95% CI 1.13–2.19, p = 0.007). One-year mortality was 9.9% (n = 11). Compared to the literature, one-year mortality was lower than expected, particularly in the intervention group. Conclusions: Single assessment tools did not have the power to predict mortality. Similar to other trials, a combination of different scores can assess the risk of mortality.
Full article
(This article belongs to the Special Issue Aortic Valve Disease: Current Evolution and Future Opportunities)
Open AccessArticle
Implementation of Intraoperative Cone-Beam CT (Loop-X) in an Established Robotic-Assisted Pedicle Screw Program: An Epoch-Based Cohort Study
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Julien N. Jost, Kristina Catalano, Jaqueline Lattmann, Debora Cipriani, Thomas Rhomberg, Lukas Andereggen, Gerrit A. Schubert and Markus Bruder
J. Clin. Med. 2026, 15(10), 3749; https://doi.org/10.3390/jcm15103749 - 13 May 2026
Abstract
Background/Objectives: Reliable intraoperative imaging is essential for robotic-assisted (RA) pedicle screw placement. Mobile intraoperative cone-beam CT (iCBCT) systems like Loop-X have been introduced into RA workflows, but implementation data remain limited. We evaluated whether Loop-X introduction was associated with efficiency or safety,
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Background/Objectives: Reliable intraoperative imaging is essential for robotic-assisted (RA) pedicle screw placement. Mobile intraoperative cone-beam CT (iCBCT) systems like Loop-X have been introduced into RA workflows, but implementation data remain limited. We evaluated whether Loop-X introduction was associated with efficiency or safety, and whether associations differed by surgeon experience. Methods: We performed a retrospective epoch-based cohort study of 146 patients undergoing RA pedicle screw placement using 3D C-arm navigation (3D-BV) or Loop-X iCBCT. Outcomes were operating room (OR) time, estimated blood loss (EBL), and length of stay (LOS). The safety endpoint was 30-day complications (Clavien–Dindo grade III or higher). Multivariable regression models adjusted for patient- and procedure-related covariates; the complication model was kept parsimonious because of the limited number of events. Interaction terms tested surgeon experience. Results: After adjustment, implementation phase was not independently associated with OR time (β 30.76 min, 95% CI −31.97 to 93.48; p = 0.33), EBL (β −19.94 mL, 95% CI −287.01 to 247.14; p = 0.88), or LOS (β 3.21 days, 95% CI −3.31 to 9.72; p = 0.33). No significant interaction with surgeon experience was detected. Major complications occurred in 16 of 146 cases (11.0%) and were not associated with Loop-X implementation (OR 0.41, 95% CI 0.10–1.74; p = 0.224). Patient factors and procedural complexity were the main determinants of outcomes. Conclusions: In this cohort, Loop-X implementation in an RA pedicle screw program was not associated with deterioration in perioperative efficiency or short-term safety after adjustment. These findings support feasibility in practice, but do not establish superiority, equivalence, or imaging-specific effects.
Full article
(This article belongs to the Special Issue Precision and Innovation in Spine Surgery: Advanced Techniques for Spinal Disorders)
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Exploring the Association of Systolic Blood Pressure and Intracranial Pressure Variability and Subarachnoid Hemorrhage Patient Outcomes
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Stephanie Cardona, Saad Pirzada, Jane Quackenbush, Joshua Olexa, Abbey Kim, Yiting Lin and Quincy K. Tran
J. Clin. Med. 2026, 15(10), 3748; https://doi.org/10.3390/jcm15103748 - 13 May 2026
Abstract
Background: Subarachnoid hemorrhage (SAH) results from extravasation of blood into the subarachnoid space and is associated with high morbidity and mortality. This study aimed to compare systolic blood pressure variability (SBPV) and intracranial pressure variability (ICPV) in three 8 h intervals during
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Background: Subarachnoid hemorrhage (SAH) results from extravasation of blood into the subarachnoid space and is associated with high morbidity and mortality. This study aimed to compare systolic blood pressure variability (SBPV) and intracranial pressure variability (ICPV) in three 8 h intervals during the first 24 h after hospital admission and investigate their associations with discharge disposition and in-hospital mortality. Methods: We retrospectively reviewed charts of adult patients with spontaneous, non-traumatic SAH admitted for at least 24 h from 2016 to 2020. Hourly measurements were recorded for both systolic blood pressure (SBP) and intracranial pressure (ICP), and SBPV and ICPV were measured using successive variation (SV) and standard deviation (SD). Results: A total of 240 patients were included (mean age 57 ± 14.2 years, 64.6% female); 40 (16.7%) died. Univariate analyses showed higher SBP-SV (22.7 ± 13.8) in the first 8 h to be significantly associated with mortality (p = 0.028) and not being discharged home (p = 0.022), compared to those who survived (17.6 ± 7.5) or were discharged home (16.7 ± 5.5). Multivariate logistic regression did not show an association between SBPV and outcomes of interest. Conclusions: Greater early SBPV was associated with mortality in univariate analysis but was not independently predictive after adjustment for clinical severity, suggesting it reflects underlying physiologic instability rather than an independent prognostic factor in SAH.
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(This article belongs to the Special Issue Current Trends and Prospects of Critical Emergency Medicine)
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Open AccessArticle
First-Line Faricimab in Diabetic Macular Edema: Insights from a Real-World Treatment-Naïve Population in Austria
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Paul Widmann-Sedlnitzky, Kim Lien Huber, Irene Steiner, Heiko Stino, Laura Kunze, Tilman Schmoll, Bianca S. Gerendas, Katharina Kriechbaum, Stefan Sacu and Andreas Pollreisz
J. Clin. Med. 2026, 15(10), 3747; https://doi.org/10.3390/jcm15103747 - 13 May 2026
Abstract
Background: Diabetic macular edema (DME) is a leading cause of vision loss. Although real-world data on faricimab, a bispecific antibody targeting vascular endothelial growth factor-A and Angiopoietin-2, are expanding, its long-term durability in routine clinical practice has not yet been fully established.
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Background: Diabetic macular edema (DME) is a leading cause of vision loss. Although real-world data on faricimab, a bispecific antibody targeting vascular endothelial growth factor-A and Angiopoietin-2, are expanding, its long-term durability in routine clinical practice has not yet been fully established. We evaluated effectiveness, anatomic response and treatment durability of first-line faricimab in treatment-naïve DME. Methods: We conducted a single-center, retrospective cohort study of treatment-naïve DME eyes initiated on intravitreal faricimab (August 2023–October 2024) in a real-world setting. After a loading phase, eyes were managed with a treat-and-extend or pro re nata regimen. The primary endpoint was retreatment interval at 48 weeks. Secondary endpoints were retreatment interval at weeks 12, 24 and 36; change in visual acuity (VA); central subfield thickness (CST); and optical coherence tomography (OCT) fluid. Results: Fifty-two eyes from 40 consecutive patients were included (baseline VA 65.96 ± 13.55 letters; CST 426.56 ± 106.72 µm). Mean injections were 4.02 ± 1.11 between months 1–6 and 1.90 ± 0.98 between months 7–12. VA improved by +8.46, +7.57, +7.65 and +7.72 letters at 12, 24, 36, and 48 weeks (all p < 0.0001), respectively. Relative CST decreased by −28.05%, −27.01%, −29.46% and −25.22% at the same time points (all p < 0.0001). At week 48, 15.4% of eyes were on a treatment interval of less than 12 weeks, 23.1% were between 12 and 16 weeks, and 46.1% were on 16 or more weeks; 15.4% were managed PRN. Conclusions: First-line faricimab in treatment-naïve DME in a real-world setting yielded clinically meaningful and durable extensions in treatment intervals, alongside sustained functional and anatomical improvements.
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(This article belongs to the Section Ophthalmology)
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Mental-Health-Related Temporary Work Disability Among Informal Caregivers During the COVID-19 Lockdown in Spain (March–June 2020): A Nationwide Occupational Health Study
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Eva María Gutiérrez Naharro, José Fernández Sáez, Raquel Ayuso Margañon, Ana María Montserrat Gala, José Ponce Blandón and Amalia Sillero Sillero
J. Clin. Med. 2026, 15(10), 3746; https://doi.org/10.3390/jcm15103746 - 13 May 2026
Abstract
Background/Objectives: During the first COVID-19 lockdown, the sudden disruption of formal care services substantially increased reliance on informal caregiving. Emerging evidence suggests that increased caregiving demands may have contributed to a higher burden of mental-health-related temporary work disability; however, population-based data from
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Background/Objectives: During the first COVID-19 lockdown, the sudden disruption of formal care services substantially increased reliance on informal caregiving. Emerging evidence suggests that increased caregiving demands may have contributed to a higher burden of mental-health-related temporary work disability; however, population-based data from occupational health systems remain limited. This study aimed to quantify and characterise, descriptively, the sociodemographic, clinical, and territorial characteristics of mental-health-related temporary work disability among workers with informal caregiving responsibilities in Spain during the first COVID-19 lockdown, and to descriptively examine differences between episodes occurring among workers with and without caregiving responsibilities. Methods: A retrospective descriptive study was conducted using anonymised nationwide occupational health records from Mutua Asepeyo. All episodes of temporary work disability certified for mental and behavioural disorders (ICD-10 F00–F99) between 14 March and 21 June 2020 were analysed. Caregiver status was determined based on documented informal caregiving responsibilities recorded within the occupational disability records. Sociodemographic, occupational, clinical, and territorial variables were examined using descriptive statistics and non-parametric tests. Results: A total of 2857 caregiver-associated episodes were identified, representing 55.6% (95% CI: 54.2–57.0) of all mental-health-related temporary work disability episodes during the study period. The majority involved women (68.1%) and caregivers of older dependent adults (59.3%). Generalised anxiety disorder was the most frequent diagnosis, followed by adjustment disorders and acute stress reactions, with significant differences by sex and employment regime. Marked territorial variability was observed, as well as longer durations of temporary work disability in specific regions and among women. Conclusions: A substantial proportion of mental-health-related temporary work disability episodes during the lockdown occurred among workers with informal caregiving responsibilities, particularly women and those caring for older dependents. These findings suggest that informal caregiving may be a determinant of occupational mental health during crises. However, given the descriptive and unadjusted nature of the study, no causal inferences can be drawn. Further research is needed to understand these associations better and inform future occupational health strategies.
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(This article belongs to the Section Mental Health)
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Proteomic Biomarkers in VTE: From Discovery to Clinical Translation
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Tengyi Cai, Prahlad Ho and Julie Wang
J. Clin. Med. 2026, 15(10), 3745; https://doi.org/10.3390/jcm15103745 - 13 May 2026
Abstract
Background: Venous thromboembolism (VTE) remains a leading cause of global morbidity and mortality. The pathophysiological mechanisms leading to VTE are still not fully elucidated. Diagnostic biomarkers for VTE lack specificity, and biomarkers to guide the duration of anticoagulation therapy have not yet
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Background: Venous thromboembolism (VTE) remains a leading cause of global morbidity and mortality. The pathophysiological mechanisms leading to VTE are still not fully elucidated. Diagnostic biomarkers for VTE lack specificity, and biomarkers to guide the duration of anticoagulation therapy have not yet entered routine clinical practice. Proteomics has emerged as a high-throughput approach for novel biomarker discovery, offering insights into the complex biological processes across the VTE continuum. This review explores current VTE proteomic research and discusses the challenges and gaps hindering clinical translation. Methods: We performed a narrative review based on a search of Scopus and PubMed for original human proteomic studies published between 1995 and July 2025. Results were limited to whole-blood, plasma or serum-based studies. Results: A total of 1190 studies were retrieved, of which 27 studies were included in this review. Studies were mainly plasma-based. Studies compared VTE patients to non-VTE controls, different VTE subtypes, and various provoked VTE cohorts. Broad themes identified proteomic signatures involving dysregulated coagulation, complement activation, inflammation, and platelet activation. Conclusions: Current proteomic evidence supports VTE as a systemic immunothrombotic disorder that shows key differences even years before developing VTE. Proteomic research in VTE holds the promise to identify biomarkers that may aid in the diagnosis and guide management of VTE. However, most proteomic findings remain exploratory to date and methodologies are varied across studies. Future studies should prioritise the workflow standardisation and validate promising biomarker panels in large-scale, prospective, longitudinal cohorts.
Full article
(This article belongs to the Special Issue Thrombosis and Haemostasis: Clinical Advances)
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Microbiological Profile of Periprosthetic Infections Following Femoral Fracture: A Retrospective Analysis
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Luca Bianco Prevot, Edoardo Verme, Livio Pietro Tronconi, Francesco Busardò and Giuseppe Basile
J. Clin. Med. 2026, 15(10), 3744; https://doi.org/10.3390/jcm15103744 - 13 May 2026
Abstract
Background: Implant-related infection following femoral fracture surgery is a severe complication in elderly patients and is associated with high morbidity and mortality. Most available evidence on periprosthetic joint infection (PJI) derives from elective arthroplasty populations, which differ substantially from patients undergoing surgery
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Background: Implant-related infection following femoral fracture surgery is a severe complication in elderly patients and is associated with high morbidity and mortality. Most available evidence on periprosthetic joint infection (PJI) derives from elective arthroplasty populations, which differ substantially from patients undergoing surgery for femoral fractures. This study aimed to investigate the microbiological profile and clinical characteristics of implant-related infections after proximal femoral fracture surgery. Materials and Methods: A retrospective observational study was conducted on 20 patients aged ≥70 years who developed implant-related infection after surgical treatment of proximal femoral fractures between 2020 and 2025 at a referral trauma center. Surgical procedures included intramedullary nailing, hemiarthroplasty, and total hip arthroplasty. Only patients with Charlson Comorbidity Index ≥ 4 and infection occurring within one year of the index surgery were included. Clinical, surgical, microbiological, and antibiotic therapy data were retrospectively reviewed. Results: The cohort had a mean age of 82.4 years and a high comorbidity burden (mean Charlson index 4.8). The most frequently isolated pathogen was Staphylococcus aureus (25.9%), with 85% methicillin-resistant strains. Other pathogens included Enterococcus faecalis, Klebsiella pneumoniae, and Escherichia coli. Polymicrobial infections were observed in 25% of patients. One-year mortality was 25%. Conclusions: Implant-related infections after femoral fracture surgery represent a distinct clinical entity compared with elective PJI, characterized by frail patients and a higher prevalence of multidrug-resistant organisms. These findings highlight the need for tailored preventive and therapeutic strategies in this high-risk population.
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(This article belongs to the Special Issue Clinical Advances in Prosthetic Joint Infection)
Open AccessArticle
Uromodulin and Tryptophan Metabolite Clearance in Hemodialyzed Patients
by
Izabela Zakrocka, Małgorzata Kozioł, Marta Więckowska-Deroń, Sylwia Boczkowska, Renata Kloc, Tomasz Kocki, Alina Olender, Ewa M. Urbańska, Wojciech Załuska and Andreas Kronbichler
J. Clin. Med. 2026, 15(10), 3743; https://doi.org/10.3390/jcm15103743 - 13 May 2026
Abstract
Background: Certain metabolites of the tryptophan-kynurenine (Trp-KYN) pathway, which are primarily cleared via tubular transport, have been linked to end-stage kidney disease (ESKD). Uromodulin—a protein expressed exclusively in the kidneys—is a key regulator of renal structure and function, as well as a
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Background: Certain metabolites of the tryptophan-kynurenine (Trp-KYN) pathway, which are primarily cleared via tubular transport, have been linked to end-stage kidney disease (ESKD). Uromodulin—a protein expressed exclusively in the kidneys—is a key regulator of renal structure and function, as well as a direct marker of tubular health. This preliminary study explores the hypothesis that serum uromodulin correlates with Trp-KYN metabolites, potentially revealing new pathophysiological pathways in patients undergoing kidney replacement therapy (KRT). Given the link between serum uromodulin, Trp-KYN metabolites, and tubular function, we examined their correlation in KRT patients. Furthermore, we assessed how various clinical and dialysis parameters influence serum uromodulin levels. Methods: A total of 64 stable patients from a single dialysis center receiving hemodialysis (HD) or hemodiafiltration (HDF) were enrolled. Pre- and post-dialysis concentrations of uromodulin, Trp, KYN, kynurenic acid (KYNA), 3-hydroxykynurenine (3-OHKYN), and their reduction ratios (RRs) were established. High-performance liquid chromatography (HPLC) was used to estimate the KYN pathway metabolite levels, whereas uromodulin concentration was measured using an immunoenzymatic assay. Results: Detectable serum uromodulin was found in only 30 patients. This group was predominantly male (p < 0.001) and characterized by shorter dialysis vintage (p < 0.001), a higher prevalence of residual kidney function (RKF) (p = 0.001) and diabetes mellitus (p = 0.028), higher pre-dialysis serum phosphorus levels (p = 0.015), and more frequent use of loop diuretics (p = 0.004). Furthermore, univariate analysis revealed significantly higher pre-dialysis (p = 0.004) and post-dialysis (p = 0.025) serum Trp concentrations in the uromodulin-positive group. Pre-dialysis serum uromodulin concentration correlated positively with pre-dialysis Trp level (p < 0.001) and negatively with the pre-dialysis KYN/Trp ratio (p = 0.008), but not with other metabolites that are also subject to tubular transport mechanisms. Post-dialysis uromodulin levels correlated positively only with post-dialysis Trp level (p = 0.005). Patients treated with HDF had significantly higher RR for uromodulin than those treated with HD (p = 0.01). Conclusions: The presented data indicate that serum uromodulin levels are correlated with RKF. Additionally, the presence of detectable serum uromodulin may indicate reduced immunological activation, leading to diminished activity within the Trp-KYN pathway.
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(This article belongs to the Section Nephrology & Urology)
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Open AccessReview
Myocardial Fibrosis in Cardiovascular Disease: An Integrative Biomarker–Imaging Framework Linking Molecular Mechanisms to Structural Phenotypes
by
Mateusz Świątko, Jakub Marek Baran, Aleksandra Czernicka, Łukasz Dudek, Maria Szewczyk, Jan Pietruszka, Łukasz Łazarowicz, Wacław Kochman and Ewelina A. Dziedzic
J. Clin. Med. 2026, 15(10), 3742; https://doi.org/10.3390/jcm15103742 - 13 May 2026
Abstract
Background: Myocardial fibrosis (MF) is a dynamic remodeling process characterized by excessive extracellular matrix (ECM) deposition, fibroblast activation, and dysregulated matrix turnover. Although initially reparative, persistent fibrotic remodeling promotes myocardial stiffening, electrical instability, and progressive cardiac dysfunction across diverse cardiovascular diseases. Circulating
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Background: Myocardial fibrosis (MF) is a dynamic remodeling process characterized by excessive extracellular matrix (ECM) deposition, fibroblast activation, and dysregulated matrix turnover. Although initially reparative, persistent fibrotic remodeling promotes myocardial stiffening, electrical instability, and progressive cardiac dysfunction across diverse cardiovascular diseases. Circulating biomarkers reflecting collagen synthesis, degradation, proteolytic regulation, and inflammatory activation have emerged as potential tools for assessing fibrotic activity and risk stratification. Methods: This targeted narrative review was based on manually guided searches of PubMed and Scopus, supplemented by citation chaining and inclusion of landmark mechanistic and translational studies. Publications addressing myocardial extracellular matrix remodeling, circulating fibrosis-related biomarkers and imaging-derived fibrosis phenotypes were selected for qualitative synthesis. Results: Myocardial fibrosis reflects interconnected inflammatory, neurohormonal, oxidative, and extracellular matrix remodeling pathways. Among circulating biomarkers, C-terminal propeptide of procollagen type I (PICP) showed the most consistent association with myocardial collagen burden and adverse outcomes, whereas carboxy-terminal telopeptide of type I collagen (CITP), matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), galectin-3, osteopontin, soluble suppression of tumorigenicity 2 (sST2), and natriuretic peptides provided more context-dependent signals. Standalone interpretation remains limited by restricted cardiac specificity, renal dysfunction, systemic inflammation, assay heterogeneity, and lack of standardized thresholds. Integration with cardiac magnetic resonance (CMR)-derived late gadolinium enhancement (LGE), T1 mapping, and extracellular volume (ECV) may improve biological and structural phenotyping. Conclusions: Circulating biomarkers capture complementary dimensions of myocardial remodeling but cannot replace structural imaging. We propose an updated, hypothesis-generating biomarker–imaging framework integrating inflammatory activation, collagen turnover, matrix quality, hemodynamic stress, and structural imaging to support phenotypic stratification and future validation of antifibrotic strategies.
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(This article belongs to the Special Issue Heart Failure: Challenges and Future Options)
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Open AccessReply
Reply to Schouten et al. Comment on “Bilika et al. Applying Nociplastic Pain Criteria in Chronic Musculoskeletal Conditions: A Vignette Study. J. Clin. Med. 2025, 14, 1179”
by
Paraskevi Bilika, Jo Nijs, Evdokia Billis, Zacharias Dimitriadis, Achilleas Paliouras, Konstantina Savvoulidou, Nikolaos Strimpakos and Eleni Kapreli
J. Clin. Med. 2026, 15(10), 3741; https://doi.org/10.3390/jcm15103741 - 13 May 2026
Abstract
We thank the authors for their constructive comments on our work [...]
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(This article belongs to the Section Clinical Neurology)
Open AccessComment
Comment on Bilika et al. Applying Nociplastic Pain Criteria in Chronic Musculoskeletal Conditions: A Vignette Study. J. Clin. Med. 2025, 14, 1179
by
Jelle C. Schouten, Frank J. P. M. Huygen and Jitske Tiemensma
J. Clin. Med. 2026, 15(10), 3740; https://doi.org/10.3390/jcm15103740 - 13 May 2026
Abstract
We read with great interest the study by Bilika et al [...]
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(This article belongs to the Section Clinical Neurology)
Open AccessReview
Sirolimus Treatment for Complex Fetal and Neonatal Vascular Anomalies: Emerging Evidence and Safety Considerations
by
Elena Țarcă, Elena Cojocaru, Lăcrămioara Ionela Butnariu, Solange Tamara Roșu, Alina Costina Luca, Sidonia Susanu, Vasile Valeriu Lupu, Eduard Vasile Roșu, Paula Popovici and Viorel Țarcă
J. Clin. Med. 2026, 15(10), 3739; https://doi.org/10.3390/jcm15103739 - 13 May 2026
Abstract
Background: Vascular abnormalities (VAs) are a broad category of disorders that include vascular malformations (inadequate embryologic blood vessel development) and vascular tumors (characterized by vascular cell hyperplasia). This sometimes-complicated pathology is increasingly being treated with mTOR inhibitors, particularly sirolimus (rapamycin). Only a
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Background: Vascular abnormalities (VAs) are a broad category of disorders that include vascular malformations (inadequate embryologic blood vessel development) and vascular tumors (characterized by vascular cell hyperplasia). This sometimes-complicated pathology is increasingly being treated with mTOR inhibitors, particularly sirolimus (rapamycin). Only a limited number of neonates treated with sirolimus have been reported in the literature to date, and there is no consensus regarding the optimal treatment regimen for vascular anomalies in this population. The objective of our narrative review is to summarize the most recent information from the specialized literature regarding the efficacy and safety of sirolimus in newborns. Methods: A methodological search was performed through the available data concerning the indications and safety when using sirolimus to treat VAs in newborns. We evaluated articles from the Embase and PubMed academic search engines using the following search terms: (vascular anomalies OR vascular tumors OR venous malformations OR lymphatic malformations OR capillary malformations) AND (neonate) AND (sirolimus OR rapamycin). Results: We identified a lack of consensus regarding indications for treatment initiation, optimal dosing regimens, and duration of therapy. In most published studies, neonates were analyzed within broader pediatric cohorts that included patients up to 18 years of age, rather than as a distinct population. Moreover, only a limited number of investigations have specifically focused on neonates treated with sirolimus and evaluated outcomes from a neonatal subgroup perspective. The available evidence largely consists of isolated case series and reports describing sirolimus use in fetuses and neonates, most commonly for lymphatic malformations or kaposiform hemangioendothelioma; in some instances, sirolimus was administered in combination with propranolol, corticosteroids, or other therapeutic modalities. Nevertheless, across studies and case reports involving fetuses or neonates, sirolimus is generally reported to be effective and well tolerated, with adverse effects that are minimal and reversible. Conclusions: For neonates and even fetuses with large, complex VAs, sirolimus appears to be an effective treatment with no serious adverse events reported to date. Decisions regarding off-label sirolimus initiation should be made by a multidisciplinary team, and parents must be thoroughly informed about potential adverse events. Well-designed randomized controlled trials or high-quality observational studies are needed to further evaluate the efficacy and safety of sirolimus in the neonatal population.
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(This article belongs to the Section Clinical Pediatrics)
Open AccessArticle
Longitudinal Quality-of-Life Trajectories Following Laparoscopic Distal Gastrectomy: A Comparison Between Billroth I and II Reconstruction Using the KOQUSS-40 Questionnaire
by
Jae Yeong Yang, Ji Yeon Park, Oh Kyoung Kwon and Ki Bum Park
J. Clin. Med. 2026, 15(10), 3738; https://doi.org/10.3390/jcm15103738 - 13 May 2026
Abstract
Background/Objectives: Although Billroth I (BI) and Billroth II (BII) are standard reconstructions after distal gastrectomy, evidence on their longitudinal quality-of-life (QoL) trajectories remains inconclusive. This study compared postoperative QoL patterns between BI and BII groups using a validated gastric cancer-specific instrument. Methods: We
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Background/Objectives: Although Billroth I (BI) and Billroth II (BII) are standard reconstructions after distal gastrectomy, evidence on their longitudinal quality-of-life (QoL) trajectories remains inconclusive. This study compared postoperative QoL patterns between BI and BII groups using a validated gastric cancer-specific instrument. Methods: We analyzed 234 patients (BI n = 51, BII n = 183) who underwent laparoscopic distal gastrectomy. QoL was assessed using the KOQUSS-40 questionnaire at 1, 3, 6, 9, and 12 months postoperatively. To address selection bias, inverse probability of treatment weighting (IPTW) was applied alongside linear mixed-effects models to evaluate group effects and group × time interactions. Results: A significant main effect of group was observed (p = 0.032), with the BII group maintaining higher total scores. These findings remained consistent after IPTW adjustment. While the overall group × time interaction was not significant (p = 0.846), indicating parallel recovery trajectories, significant interactions were identified in specific domains, including dumping syndrome and constipation. In these domains, the BI group showed gradual improvement, whereas the BII group exhibited relatively stable scores. Conclusions: While both reconstruction methods demonstrated comparable overall QoL trajectories with no significant group × time interaction, the KOQUSS-40 revealed exploratory differences in specific symptom domains, notably dumping-related symptoms and constipation. These findings provide clinically meaningful insights for postoperative patient counseling, enabling tailored expectations during the first year after distal gastrectomy. However, these domain-specific results should be regarded as hypothesis generating and interpreted with caution.
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(This article belongs to the Section General Surgery)
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Open AccessArticle
Impact of Joint Line Displacement on Function and Quality of Life After Primary Total Knee Arthroplasty
by
Eugenio Miguel Ferrer Santacreu, Sara López Resino, Yentl Garcelán Pecharromán and Pablo Cendrero Cendrero
J. Clin. Med. 2026, 15(10), 3737; https://doi.org/10.3390/jcm15103737 - 13 May 2026
Abstract
Background/Objectives: Total knee arthroplasty (TKA) is one of the most common surgeries among people over 60. Joint line restoration plays an important role in knee biomechanics, with joint line elevation or depression after TKA being associated with poorer postoperative outcomes, although there is
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Background/Objectives: Total knee arthroplasty (TKA) is one of the most common surgeries among people over 60. Joint line restoration plays an important role in knee biomechanics, with joint line elevation or depression after TKA being associated with poorer postoperative outcomes, although there is no consensus regarding the threshold at which these variations become clinically relevant. The objectives of this study were to evaluate whether a joint line variation greater than 4 mm after primary TKA affects postoperative outcomes, and to assess the concordance between different radiographic methods used to measure joint line height. Methods: A retrospective study was conducted including patients over 60 who underwent primary TKA for knee osteoarthritis. Joint line height variations were evaluated preoperatively and postoperatively using three radiographic measurements: lateral femoral epicondyle–fibular head (LEFH) distance, adductor tubercle–joint line (ATJL) distance, and Blackburne–Peel index. Quality of life was assessed using the Short Form-12 (SF-12) questionnaire, and functionality using the Knee Society Score (KSS). Statistical analysis was carried out using R software. Results: Seventy-three patients were included. No statistically significant associations were found between joint line displacement and functional outcomes (KSS), quality of life (SF-12), or postoperative complications. Concordance analysis between radiographic methods showed a significant but weak correlation between the LEFH and ATJL measurements (ρ = 0.419; p < 0.001). Conclusions: Joint line displacement after primary TKA was not associated with poorer postoperative outcomes in this cohort. These findings suggest that its clinical impact may depend more on its magnitude than on its mere presence and may also be influenced by additional factors. The weak concordance observed between radiographic measurement methods highlights the need for standardized criteria.
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(This article belongs to the Special Issue Clinical Management of Knee Arthroplasty)
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