Biomechanical and Biological Factors of Sexual Dimorphism in Anterior Knee Pain: Current Concepts.

Female gender is one of the commonly mentioned risk factors for anterior knee pain (AKP), among a spectrum of other factors including anatomical, biomechanical, hormonal, behavioral, and psychological elements contributing to its development. Despite the focus on individual risk factors, there's a notable gap in comprehending how gender influences and interacts with other risk factors. The objective of this review was to identify and emphasize the connections between these interactions, gender-related risk factors for AKP, and the potential mechanisms that explain their associations with other risk factors, aiming to aid in the creation of precise prevention and treatment approaches. Gender influences the majority of risk factors for AKP, including anatomical, biomechanical, hormonal, behavioral, and psychological factors. Women have on average smaller patellae, higher patellofemoral cartilage stress and for AKP, disadvantageous trochlear morphology, ligament and muscle composition and unfavorable neuromuscular control pattern. In contrast, men show on average an increased ability to strengthen their hip external rotators, which are both protective against AKP. Particularly in kinetic and kinematic analysis, men have been shown to have a distinctly different risk factor profile than women. Sex hormones may also play a role in the risk of AKP, with estrogen potentially influencing ligamentous laxity, increasing midfoot loading and affecting neuromuscular control of the lower extremities and testosterone positively affecting muscle mass and strength. The higher incidence of AKP in women is likely due to a combination of slightly increased risk factors. Although all risk factors can be present in both men and women and the holistic evaluation of each individual's risk factor composition is imperative regardless of gender, knowing distinctive risk factors may help with focused evaluation, treatment, and implementing preventive measures of AKP.

Editorial Commentary: Absent Extreme Bony Malalignment: Medial Patellofemoral Reconstruction Is a Sufficient Primary Surgery for Adolescents With Recurrent Patella Instability.

When planning an adolescent's primary surgery for recurrent patella instability, the surgeon must weigh the failure risk of performing medial patellofemoral reconstruction (MPFLR) versus the potential morbidity of adding a concomitant bony procedure, such as tibial tubercle osteotomy. In this age group, isolated MPFLR is an excellent operation with high clinical success, low failure rates, and favorable complication profile. Patients with high grade J-sign and severe trochlea dysplasia, apprehension into deep flexion, and extremes of bony malalignment, including elevated tibial tubercle-trochlear groove distance, may benefit from "doing more" than MPFLR alone. Other factors to be considered include patella alta, generalized ligament laxity, femoral rotation, tibial torsion, and valgus malalignment. In challenging situations, such as syndromic patients (e.g., neuromuscular disorders), congenital (habitual) patella dislocation, fixed dislocations, and failed prior to MPFLR, a combined surgical approach is likely needed. Patients who require "unloading" for symptomatic chondrosis also benefit from combined bony and soft tissue surgery. However, for the majority of patients with recurrent instability and no prior surgery, an isolated soft tissue reconstruction is a rational, safe, efficient, and evidence-based selection.

Dynamic versus static medial patellofemoral ligament reconstruction technique in the treatment of recurrent patellar dislocation: a randomized clinical trial protocol.

BACKGROUND: The redislocation rate of conservatively treated patella instability is high. One of the leading surgical strategies is medial patellofemoral ligament reconstruction. Over-tensioning is one of the most challenging complications in static medial patellofemoral ligament reconstruction as the graft used for reconstruction is isometric and the anatomical MPFL is a mostly dynamic structure. As an alternative to established static reconstruction techniques, dynamic graft techniques have been introduced for stabilizing the patella with the aim of providing a more physiological reconstruction of the medial patellofemoral ligament. To date, data on clinical outcomes are scarce and on biomechanical outcomes of the dynamic MPFL reconstruction are lacking. Here, we present the protocol of a randomized clinical trial for comparing clinical and biomechanical outcomes of dynamic versus static medial patellofemoral ligament reconstruction. METHODS: This study is a prospective, single blinded, randomized, multicenter, multimodal (clinical and biomechanical) clinical trial. Patients with recurrent patella dislocation requiring isolated MPFL reconstruction will be recruited and randomized to the dynamic or static reconstruction technique. Participants will be followed up for 2 years with a total of five follow-ups. Preoperative magnetic resonance imaging, upright radiographs, surgical reports and patient records will be evaluated, and clinical and functional outcomes will be measured. Patient-reported knee function and anterior knee pain as assessed with the Kujala score will serve as primary outcome. For biomechanical outcome, pre- and postoperative evaluations will be performed to assess isokinetic muscle strength, gait asymmetry, joint kinematics and kinetics, and timing of muscle activity. DISCUSSION: The results of the study will clarify whether the reported surgery success for patella stabilization via dynamic MPFL reconstruction is due to muscle contraction or to the passive tenodesis effect combined with clinical outcome measures. With this study, we will provide much needed information on knee biomechanics after dynamic versus static MPFL reconstruction to provide evidence to support orthopedic surgeons in evidence-based decision-making in their quest for surgical techniques most favorable for their patients. Trial registration The study protocol was registered at clinicaltrials.gov (NCT04849130). Registered 19 April 2021, https://clinicaltrials.gov/ct2/show/NCT04849130 .

Dual-Energy CT Vital Iodine Tumor Burden for Response Assessment in Patients With Metastatic GIST Undergoing TKI Therapy: Comparison With Standard CT and FDG PET/CT Criteria.

BACKGROUND. CT-based criteria for assessing the gastrointestinal stromal tumor (GIST) response to tyrosine kinase inhibitor (TKI) therapy are limited in part because tumor attenuation is influenced by treatment-related changes including hemorrhage and calcification. The iodine concentration may be less impacted by such changes. OBJECTIVE. The purpose of this study was to determine whether the dual-energy CT (DECT) vital iodine tumor burden (TB) allows improved differentiation between treatment responders and nonresponders among patients with metastatic GIST who are undergoing TKI therapy compared with established CT and PET/CT criteria. METHODS. An anthropomorphic phantom with spherical inserts mimicking GIST lesions of varying iodine concentrations and having nonenhancing central necrotic cores underwent DECT to determine a threshold iodine concentration. Forty patients (25 women and 15 men; median age, 57 years) who were treated with TKI for metastatic GIST were retrospectively evaluated. Patients underwent baseline and follow-up DECT and FDG PET/CT. Response assessment was performed using RECIST 1.1, modified Choi (mChoi) criteria, vascular tumor burden (VTB) criteria, DECT vital iodine TB criteria, and European Organization for Research and Treatment of Cancer (EORTC) PET criteria. DECT vital iodine TB criteria used the same percentage changes as RECIST 1.1 response categories. Progression-free survival was compared between responders and nonresponders for each response criterion by use of Cox proportional hazard ratios and Harrell C-indexes (i.e., concordance indexes). RESULTS. The phantom experiment identified a threshold of 0.5 mg/mL to differentiate vital from nonvital tissue. With use of the DECT vital iodine TB, median progression-free survival was significantly different between responders and nonresponders (623 vs 104 days; p < .001).. For nonresponders versus responders, the hazard ratio for disease progression for DECT vital iodine TB was 6.9 versus 7.6 for EORTC PET criteria, 3.3 for VTB criteria, 2.3 for RECIST 1.1, and 2.1 for mChoi criteria. The C-index was 0.74 for EORTC PET criteria, 0.73 for DECT vital iodine TB criteria, 0.67 for VTB criteria, 0.61 for RECIST 1.1, and 0.58 for mChoi criteria. The C-index was significantly greater for DECT vital iodine TB criteria than for RECIST 1.1 (p = .02) and mChoi criteria (p = .002), but it was not different from that for VTB and EORTC PET criteria (p > .05). CONCLUSION. DECT vital iodine TB criteria showed performance comparable to that of EORTC PET criteria and outperformed RECIST 1.1 and mChoi criteria for response assessment of metastatic GIST treated with TKI therapy. CLINICAL IMPACT. DECT vital iodine TB could help guide early management decisions in patients receiving TKI therapy.

Does patella alta lead to worse clinical outcome in patients who undergo isolated medial patellofemoral ligament reconstruction? A systematic review.

INTRODUCTION: The aim of this systematic review is to determine the effect of patella height on clinical outcomes after isolated MPFL reconstruction for patella instability. Our primary hypothesis is that patients with patella alta report similar outcomes after isolated MPFL reconstruction compared to patients with normal patella height. METHODS: A review of the literature was performed according to the PRISMA guidelines. PubMed, EMBASE, and the Cochrane Library were searched from inception to January 10th 2018. Studies were identified using synonyms for "medial patellofemoral ligament", "reconstruction" and "patella alta". RESULTS: The search resulted in 467 reports on PubMed, 175 on EMBASE and 3 on the Cochrane Library. We included and analyzed in detail six studies describing outcomes after isolated medial patellofemoral ligament reconstruction with regard to patellar height. We found that both patients with patella alta and normal patella height reported satisfactory outcomes after isolated medial patellofemoral ligament reconstruction. However, because of applied exclusion criteria in the included studies the total number of patients with severe patella alta was small (13/74 patients with patella alta, 18%). CONCLUSIONS: Based on the current literature we suggest that additional tibial tubercle distalisation is not mandatory in patients with mild patella alta (Caton-Deschamps Index 1.2-1.4). To assess the best indications for different surgical procedures for patients with patella instability future research is needed to develop a clear and uniform definition of relevant patella alta. LEVEL OF EVIDENCE: III.

A Systematic Literature Review of Self-Reported Smoking Cessation Counseling by Primary Care Physicians.

Tobacco consumption is a risk factor for chronic diseases and worldwide around six million people die from long-term exposure to first- or second-hand smoke annually. One effective approach to tobacco control is smoking cessation counseling by primary care physicians. However, research suggests that smoking cessation counseling is not sufficiently implemented in primary care. In order to understand and address the discrepancy between evidence and practice, an overview of counseling practices is needed. Therefore, the aim of this systematic literature review is to assess the frequency of smoking cessation counseling in primary care. Self-reported counseling behavior by physicians is categorized according to the 5A's strategy (ask, advise, assess, assist, arrange). An electronic database search was performed in Embase, Medline, PsycINFO, CINAHL and the Cochrane Library and overall, 3491 records were identified. After duplicates were removed, the title and abstracts of 2468 articles were screened for eligibility according to inclusion/exclusion criteria. The remaining 97 full-text articles reporting smoking cessation counseling by primary care physicians were assessed for eligibility. Eligible studies were those that measured physicians' self-reported smoking cessation counseling activities via questionnaire. Thirty-five articles were included in the final review (1 intervention and 34 cross-sectional studies). On average, behavior corresponding to the 5A's was reported by 65% of physicians for "Ask", 63% for "Advise", 36% for "Assess", 44% for "Assist", and 22% of physicians for "Arrange", although the measurement and reporting of each of these counseling practices varied across studies. Overall, the results indicate that the first strategies (ask, advise) were more frequently reported than the subsequent strategies (assess, assist, arrange). Moreover, there was considerable variation in the items used to assess counseling behaviour and developing a standardized instrument to assess the counseling strategies implemented in primary care would help to identify and address current gaps in practice.

Evaluating a collaborative smoking cessation intervention in primary care (ENTER): study protocol for a cluster-randomized controlled trial.

BACKGROUND: Tobacco consumption is a preventable risk factor for chronic disease and complicates the treatment of medical conditions. Therefore, the German health insurance company AOK NORDWEST has developed a collaborative smoking cessation intervention for individuals with cardiovascular disease, chronic obstructive pulmonary disease and heavy smokers, with the aim of reducing tobacco consumption. The objective of the study ENTER is to evaluate the effectiveness of the collaborative smoking cessation intervention and determine its cost-effectiveness. METHODS/DESIGN: This study is a cluster-randomized controlled trial conducted with 40 medical practices that are being selected from different geographic regions in Germany. Participating medical practices will be randomly allocated to either the intervention or control group. Within the medical practices, a total of 800 patients will be recruited for participation in the study and blinded to group assignment. Patients are included in the study if they are 18 years or older, insured by AOK, heavy smokers (smoke at least 20 cigarettes per day) and/or suffer from chronic obstructive pulmonary disease or cardiovascular disease. Exclusion criteria are patients who are nonsmokers, who have cognitive impairments or who are illiterate. Physicians from medical practices in the intervention group will motivate patients to participate in a smoking cessation program offered by the health insurance, refer them to the program and ask about their program participation. Physicians from medical practices in the control group will provide usual care. Data collection will take place on the date of study inclusion and after 6 and 12 months. The primary outcome is the amount of cigarettes consumed during the past 30 days, 12 months after the initial medical consultation. Secondary outcomes are abstinence from smoking, health-related quality of life and respiratory complaints. Moreover, a process evaluation and health economic analysis will be performed. DISCUSSION: The results of this study will help to determine whether the collaborative smoking cessation intervention is an effective and feasible way to promote smoking cessation in the primary care setting and provide evidence regarding its cost-effectiveness. TRIAL REGISTRATION: German Clinical Trials Register DRKS00006079 . Registered 4 June 2014.

Chassis organism from Corynebacterium glutamicum--a top-down approach to identify and delete irrelevant gene clusters.

For synthetic biology applications, a robust structural basis is required, which can be constructed either from scratch or in a top-down approach starting from any existing organism. In this study, we initiated the top-down construction of a chassis organism from Corynebacterium glutamicum ATCC 13032, aiming for the relevant gene set to maintain its fast growth on defined medium. We evaluated each native gene for its essentiality considering expression levels, phylogenetic conservation, and knockout data. Based on this classification, we determined 41 gene clusters ranging from 3.7 to 49.7 kbp as target sites for deletion. 36 deletions were successful and 10 genome-reduced strains showed impaired growth rates, indicating that genes were hit, which are relevant to maintain biological fitness at wild-type level. In contrast, 26 deleted clusters were found to include exclusively irrelevant genes for growth on defined medium. A combinatory deletion of all irrelevant gene clusters would, in a prophage-free strain, decrease the size of the native genome by about 722 kbp (22%) to 2561 kbp. Finally, five combinatory deletions of irrelevant gene clusters were investigated. The study introduces the novel concept of relevant genes and demonstrates general strategies to construct a chassis suitable for biotechnological application.