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ABSTRACT: We report 1- and 5-year survival after acute myeloid leukemia (AML) diagnosis and early mortality within 30 days of systemic anticancer therapy (SACT) treatments, using national cancer registry data in England. Patients aged 18 to 99 years diagnosed between 2013 and 2020 were included. Overall survival (OS) was calculated using Kaplan-Meier methodology, and adjusted hazard ratios (aHRs; adjusted for intensity of treatment, age at diagnosis, sex, ethnicity, socioeconomic deprivation, comorbidity, and year of diagnosis) using Cox proportional hazards regression. Odds of 30-day mortality (adjusted odds ratios [aORs], adjusted for aforementioned characteristics), along with performance status and body mass index, were calculated using logistic regression. Among 17 107 patients identified, older age and comorbidity were associated with worse survival. Asian and Black patients had better survival than White patients: 5-year OS of 34.6%, 29.7%, and 17.8%, respectively; aHR of 0.86; (95% confidence interval [CI], 0.77-0.96) Asian vs White, and 0.84 (95% CI, 0.73-0.96) Black vs White. Socioeconomic deprivation was associated with worse survival. Overall, 7906 (46.2%) patients were documented as having received SACT. Thirty-day mortality was lower for patients receiving intensive rather than nonintensive SACT. After adjustment for cofactors, the risk was higher in those treated intensively (aOR, 0.74; 95% CI, 0.60-0.92). We show that ethnicity and socioeconomic status affects outcomes in AML. Further work is needed to understand how these effects may differ in different health care settings, and whether this because of effects on disease biology, responsiveness to treatment, or drug toxicity. Selection of intensive vs nonintensive treatment should be based on individual patient factors, balancing improved long-term survival against higher early mortality.
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Leucemia Mieloide Aguda , Sistema de Registros , Humanos , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/tratamiento farmacológico , Inglaterra/epidemiología , Persona de Mediana Edad , Anciano , Masculino , Femenino , Adulto , Anciano de 80 o más Años , Adolescente , Adulto Joven , Resultado del Tratamiento , Demografía , Historia del Siglo XXIRESUMEN
Favourable outcomes with CPX-351 versus conventional 7 + 3 were demonstrated in the pivotal phase III trial in adults aged 60-75 years with newly diagnosed, highrisk/secondary acute myeloid leukaemia (AML). As a complement to the clinical trial and to address important data gaps, the CPX-351 Real-World Effectiveness and SafeTy (CREST-UK; NCT05169307) study evaluated the use of CPX-351 in routine clinical practice in the UK, in 147 patients with newly diagnosed therapy-related AML or AML with myelodysplasia-related changes. Best response of complete remission or complete remission with incomplete platelet or neutrophil recovery was achieved by 53% of evaluable patients. Kaplan-Meier median overall survival (OS) was 12.8 months (95% confidence interval 9.2-15.3). Fifty (34%) patients proceeded to haematopoietic cell transplantation (HCT); median OS landmarked from the HCT date was not reached. There were no new safety concerns with CPX-351 identified in CREST-UK. Patients treated with CPX-351 in the outpatient setting spent an average of 24.4, 16.7, 28.2, and 27.7 fewer days on the ward compared with inpatients during first induction, second induction, first consolidation, and second consolidation, respectively. The results from CREST-UK provide valuable insights into the effectiveness, safety, and outpatient delivery of CPX-351 in routine clinical practice in the UK.
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We report on a study of next-generation sequencing in 257 patients undergoing investigations for cytopenias. We sequenced bone marrow aspirates using a target enrichment panel comprising 82 genes and used T cells from paired blood as a control. One hundred and sixty patients had idiopathic cytopenias, 81 had myeloid malignancies and 16 had lymphoid malignancies or other diagnoses. Forty-seven of the 160 patients with idiopathic cytopenias had evidence of somatic pathogenic variants consistent with clonal cytopenias. Only 39 genes of the 82 tested were mutated in the 241 patients with either idiopathic cytopenias or myeloid neoplasms. We confirm that T cells can be used as a control to distinguish between germline and somatic variants. The use of paired analysis with a T-cell control significantly reduced the time molecular scientists spent reporting compared to unpaired analysis. We identified somatic variants of uncertain significance (VUS) in a higher proportion (24%) of patients with myeloid malignancies or clonal cytopenias compared to less than 2% of patients with non-clonal cytopenias. This suggests that somatic VUS are indicators of a clonal process. Lastly, we show that blood depleted of lymphocytes can be used in place of bone marrow as a source of material for sequencing.
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Citopenia , Síndromes Mielodisplásicos , Trastornos Mieloproliferativos , Neoplasias , Humanos , Síndromes Mielodisplásicos/genética , Mutación , Linfocitos T/patología , Trastornos Mieloproliferativos/genéticaRESUMEN
Background: Patients with persistent glenohumeral osteoarthritis symptoms despite nonoperative management may pursue anatomic total shoulder arthroplasty (TSA). TSA revision rates are higher in patients with preoperative eccentric (asymmetric posterior erosion) compared with concentric (symmetric) glenoid deformity. If posterior rotator cuff deficiency demonstrated preoperatively in patients with eccentric deformity persists after TSA, it may manifest as relative weakness in external compared with internal rotation secondary to deficient activity of the shoulder external rotator muscles. Persistent posterior rotator cuff deficiency is hypothesized to contribute to TSA failures. However, it remains unknown whether rotational strength is impaired after TSA in patients with eccentric deformity. Our goal was to determine if patients with eccentric deformity exhibit relative external rotation weakness that may be explained by posterior rotator cuff deficiency after TSA. Methods: Patients who were >1 year after TSA for primary glenohumeral osteoarthritis and had had preoperative eccentric or concentric deformity were prospectively recruited. Torque was measured and electromyography was performed during maximal isometric contractions in 26 three-dimensional direction combinations. Relative strength in opposing directions (strength balance) and muscle activity of 6 shoulder rotators were compared between groups. Results: The internal (+) and external (-) rotation component of strength balance did not differ in patients with eccentric (mean internal-external rotation component of strength balance: -7.6% ± 7.4%) compared with concentric deformity (-10.3% ± 6.8%) (mean difference: 2.7% [95% confidence interval (CI), -1.3% to 6.7%]; p = 0.59), suggesting no relative external rotation weakness. Infraspinatus activity was reduced in patients with eccentric (43.9% ± 10.4% of maximum voluntary contraction [MVC]) compared with concentric (51.3% ± 10.4% of MVC) deformity (mean difference: -7.4% [95% CI, -13.4% to -1.4%] of MVC; p = 0.04). Conclusions: A relative external rotation strength deficit following TSA was not found, despite evidence of reduced infraspinatus activity, in the eccentric-deformity group. Reduced infraspinatus activity suggests that posterior rotator cuff deficiencies may persist following TSA in patients with eccentric deformities. Longitudinal study is necessary to evaluate muscle imbalance as a contributor to higher TSA failure rates. Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
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BACKGROUND: When nonoperative measures do not alleviate the symptoms of glenohumeral osteoarthritis (OA), patients with advanced OA primarily are treated with anatomic total shoulder arthroplasty (TSA). It is unknown why TSAs performed in patients with eccentric (asymmetric glenoid wear) compared with concentric (symmetric glenoid wear) deformities exhibit higher failure rates, despite surgical advances. Persistent disruption of the posterior-to-anterior rotator cuff (RC) force couple resulting from posterior RC intramuscular degeneration in patients with eccentric deformities could impair external rotation strength and may contribute to eventual TSA failure. Pain and intramuscular fat within the RC muscles may impact external rotation strength measures and are important to consider. QUESTIONS/PURPOSES: (1) Is there relative shoulder external rotation weakness in patients with eccentric compared with concentric deformities? (2) Is there higher resting or torque-dependent pain in patients with eccentric compared with concentric deformities? (3) Do patients with eccentric deformities have higher posterior-to-anterior RC intramuscular fat percent ratios than patients with concentric deformities? METHODS: From February 2020 to November 2021, 65% (52 of 80) of patients with OA met study eligibility criteria. Of these, 63% (33 of 52) of patients enrolled and provided informed consent. From a convenience sample of 21 older adults with no history of shoulder pain, 20 met eligibility criteria as control participants. Of the convenience sample, 18 patients enrolled and provided informed consent. In total for this prospective, cross-sectional study, across patients with OA and control participants, 50% (51 of 101) of participants were enrolled and allocated into the eccentric (n = 16), concentric (n = 17), and control groups (n = 18). A 3-degree-of-freedom load cell was used to sensitively quantify strength in all three dimensions surrounding the shoulder. Participants performed maximal isometric contractions in 26 1-, 2-, and 3-degree-of-freedom direction combinations involving adduction/abduction, internal/external rotation, and/or flexion/extension. To test for relative external rotation weakness, we quantified relative strength in opposing directions (three-dimensional [3D] strength balance) along the X (+adduction/-abduction), Y (+internal/-external rotation), and Z (+flexion/-extension) axes and compared across the three groups. Patients with OA rated their shoulder pain (numerical rating 0-10) before testing at rest (resting pain; response to "How bad is your pain today?") and with each maximal contraction (torque-dependent pain; numerical rating 0-10). Resting and torque-dependent pain were compared between patients with eccentric and concentric deformities to determine if pain was higher in the eccentric group. The RC cross-sectional areas and intramuscular fat percentages were quantified on Dixon-sequence MRIs by a single observer who performed manual segmentation using previously validated methods. Ratios of posterior-to-anterior RC fat percent (infraspinatus + teres minor fat percent/subscapularis fat percent) were computed and compared between the OA groups. RESULTS: There was no relative external rotation weakness in patients with eccentric deformities (Y component of 3D strength balance, mean ± SD: -4.7% ± 5.1%) compared with patients with concentric deformities (-0.05% ± 4.5%, mean difference -4.7% [95% CI -7.5% to -1.9%]; p = 0.05). However, there was more variability in 3D strength balance in the eccentric group (95% CI volume, % 3 : 893) compared with the concentric group (95% CI volume, % 3 : 579). In patients with eccentric compared with concentric deformities, there was no difference in median (IQR) resting pain (1.0 [3.0] versus 2.0 [2.3], mean rank difference 4.5 [95% CI -6.6 to 16]; p = 0.61) or torque-dependent pain (0.70 [3.0] versus 0.58 [1.5], mean rank difference 2.6 [95% CI -8.8 to 14]; p = 0.86). In the subset of 18 of 33 patients with OA who underwent MRI, seven patients with eccentric deformities demonstrated a higher posterior-to-anterior RC fat percent ratio than the 11 patients with concentric deformities (1.2 [0.8] versus 0.70 [0.3], mean rank difference 6.4 [95% CI 1.4 to 11.5]; p = 0.01). CONCLUSION: Patients with eccentric deformities demonstrated higher variability in strength compared with patients with concentric deformities. This increased variability suggests patients with potential subtypes of eccentric wear patterns (posterior-superior, posterior-central, and posterior-inferior) may compensate differently for underlying anatomic changes by adopting unique kinematic or muscle activation patterns. CLINICAL RELEVANCE: Our findings highlight the importance of careful clinical evaluation of patients presenting with eccentric deformities because some may exhibit potentially detrimental strength deficits. Recognition of such strength deficits may allow for targeted rehabilitation. Future work should explore the relationship between strength in patients with specific subtypes of eccentric wear patterns and potential forms of kinematic or muscular compensation to determine whether these factors play a role in TSA failures in patients with eccentric deformities.
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Osteoartritis , Articulación del Hombro , Anciano , Humanos , Benzopiranos , Estudios Transversales , Osteoartritis/diagnóstico por imagen , Osteoartritis/cirugía , Fenoles , Estudios Prospectivos , Rango del Movimiento Articular/fisiología , Manguito de los Rotadores/diagnóstico por imagen , Manguito de los Rotadores/fisiología , Manguito de los Rotadores/cirugía , Articulación del Hombro/diagnóstico por imagen , Articulación del Hombro/fisiología , Articulación del Hombro/cirugía , Dolor de HombroRESUMEN
Induction therapy for acute myeloid leukaemia (AML) has changed with the approval of a number of new agents. Clinical guidelines can struggle to keep pace with an evolving treatment and evidence landscape and therefore identifying the most appropriate front-line treatment is challenging for clinicians. Here, we combined drug eligibility criteria and genetic risk stratification into a digital format, allowing the full range of possible treatment eligibility scenarios to be defined. Using exemplar cases representing each of the 22 identified scenarios, we sought to generate consensus on treatment choice from a panel of nine aUK AML experts. We then analysed >2500 real-world cases using the same algorithm, confirming the existence of 21/22 of these scenarios and demonstrating that our novel approach could generate a consensus AML induction treatment in 98% of cases. Our approach, driven by the use of decision trees, is an efficient way to develop consensus guidance rapidly and could be applied to other disease areas. It has the potential to be updated frequently to capture changes in eligibility criteria, novel therapies and emerging trial data. An interactive digital version of the consensus guideline is available.
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Leucemia Mieloide Aguda , Adulto , Consenso , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapiaRESUMEN
Accurate, reproducible diagnoses can be difficult to make in haemato-oncology due to multi-parameter clinical data, complex diagnostic criteria and time-pressured environments. We have designed a decision tree application (DTA) that reflects WHO diagnostic criteria to support accurate diagnoses of myeloid malignancies. The DTA returned the correct diagnoses in 94% of clinical cases tested. The DTA maintained a high level of accuracy in a second validation using artificially generated clinical cases. Optimisations have been made to the DTA based on the validations, and the revised version is now publicly available for use at http://bit.do/ADAtool.
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Muscle activation helps stabilize the glenohumeral joint and prevent dislocations, which are more common at the shoulder than at any other human joint. Feedforward control of shoulder muscles is important for protecting the glenohumeral joint from harm caused by anticipated external perturbations. However, dislocations are frequently caused by unexpected perturbations for which feedback control is essential. Stretch-evoked reflexes elicited by translations of the glenohumeral joint may therefore be an important mechanism for maintaining joint integrity, yet little is known about them. Specifically, reflexes elicited by glenohumeral translations have only been studied under passive conditions, and there have been no investigations of how responses are coordinated across the functional groupings of muscles found at the shoulder. Our objective was to characterize stretch-evoked reflexes elicited by translations of the glenohumeral joint while shoulder muscles are active. We aimed to determine how these responses differ between the rotator cuff muscles, which are essential for maintaining glenohumeral stability, and the primary shoulder movers, which are essential for the large mobility of this joint. We evoked reflexes using anterior and posterior translations of the humeral head while participants produced voluntary isometric torque in six directions spanning the three rotational degrees-of-freedom about the shoulder. Electromyograms were used to measure the stretch-evoked reflexes elicited in nine shoulder muscles. We found that reflex amplitudes were larger in the rotator cuff muscles than in the primary shoulder movers, in part due to increased background activation during torque generation but more so due to an increased scaling of reflex responses with background activation. The reflexes we observed likely arose from the diversity of proprioceptors within the muscles and in the passive structures surrounding the shoulder. The large reflexes observed in the rotator cuff muscles suggest that feedback control of the rotator cuff augments the feedforward control that serves to compress the humeral head into the glenoid. This coordination may serve to stabilize the shoulder rapidly when preparing for and responding to unexpected disturbances.
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OBJECTIVE: The study aim was to evaluate subacromial and internal impingement risk between shoulders (dominant/nondominant) during dynamic motion using subject-specific anatomy and precise in vivo kinematics. DESIGN: In a prospective cross-sectional study, nine subjects underwent bilateral magnetic resonance (N = 18 shoulders) and fluoroscopic imaging during elevation and external rotation at 90 degrees of abduction. Subject-specific bone models were created and distances from footprint to (a) acromion and (b) glenoid were measured to evaluate risk. RESULTS: Throughout elevation, subacromial impingement risk was greater in the dominant shoulder (P = 0.0178). Regardless of side, high subacromial impingement risk occurred at 30% (78 degrees), 50% (101 degrees), and 70% (57 degrees) of the elevation cycle (P < 0.0001). High subacromial impingement risk also occurred at 30% (94 degrees), 50% (120 degrees), and 70% (63 degrees) of the external rotation motion cycle (P < 0.0001). Throughout both motions, internal impingement risk was not observed; however, the footprint and glenoid were closest at 50% of the elevation (101 degrees) and external rotation (120 degrees) cycles (P < 0.0001). CONCLUSIONS: During elevation, subacromial impingement risk is greatest at lower arm positions (30% cycle, 78 degrees) and is greater in the dominant shoulder. High subacromial impingement risk also occurs with external rotation (63-120 degrees). Internal impingement risk does not occur with maximal elevation (101 degrees) or external rotation at 90-degree abduction but is more closely approached with elevation.
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Medición de Riesgo , Rotación , Síndrome de Abducción Dolorosa del Hombro/diagnóstico por imagen , Síndrome de Abducción Dolorosa del Hombro/fisiopatología , Articulación del Hombro/diagnóstico por imagen , Adulto , Enfermedades Asintomáticas , Estudios Transversales , Femenino , Fluoroscopía , Lateralidad Funcional/fisiología , Humanos , Imagen por Resonancia Magnética , Masculino , Estudios ProspectivosRESUMEN
BACKGROUND: There has been little documentation of the effects of total shoulder arthroplasty (TSA) on psychological status and health-related quality of life (HRQoL). We investigated changes in psychological status (depression and anxiety) and HRQoL following TSA and assessed the effect of preoperative psychological status on postoperative clinical and functional outcome. We hypothesized that TSA would improve both psychological status and HRQoL. METHODS: We prospectively enrolled 46 patients undergoing TSA for osteoarthritis. Preoperatively and at 3, 6, and 12 months postoperatively, all of the subjects completed the visual analog scale (VAS) for pain, the American Shoulder and Elbow Surgeons Scale (ASES), the Subjective Shoulder Value (SSV) measure, the Hospital Anxiety and Depression Scale (HADS), and the World Health Organization Quality of Life Scale Abbreviated Version (WHOQOL-BREF). RESULTS: From 3 months after surgery, significant improvement in HADS-depression, HADS-anxiety, and WHOQOL-BREF scores as well as in the other outcome measures of VAS pain score, ASES score, and SSV were observed. The prevalence of depression and anxiety decreased from a rate of 15.2% and 19.5%, respectively, preoperatively to a rate of 6.5% for each at 12 months postoperatively. Preoperative HADS-depression and HADS-anxiety scores did not correlate with any of the clinical and functional outcome measures at 12 months after surgery. CONCLUSIONS: This study showed significant improvement in psychological status and HRQoL as well as in pain and functional ability from 3 months after TSA in patients with osteoarthritis. Preoperative depression and anxiety did not predict poor postoperative outcome. Our findings suggest that TSA offers an excellent chance of improving psychological status and HRQoL. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
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Artroplastía de Reemplazo de Hombro/psicología , Calidad de Vida , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Trastornos de Ansiedad/etiología , Trastorno Depresivo/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteoartritis/psicología , Osteoartritis/cirugía , Estudios ProspectivosRESUMEN
PURPOSE: To evaluate glenoid version and humeral subluxation on preoperative multiplanar imaging of patients who underwent surgery for posterior glenohumeral instability compared with a matched group of patients who had shoulder surgery for other pathology. METHODS: All patients over a 2-year period who underwent surgery for posterior instability had preoperative magnetic resonance (MR) imaging or MR arthrogram reviewed. Patients undergoing shoulder surgery for reasons other than instability were identified as a control group and matched by sex, laterality, and age. Measurement of glenoid version and percentage of humeral subluxation was performed by 2 reviewers after completing a tutorial. Reviewers were blinded to diagnosis and to whether or not the patients were in the experimental or control group. RESULTS: There were 41 patients in each group. The average glenoid version in the control group was 5.6° of retroversion (standard deviation [SD] 3.0), and the average humeral subluxation was 54% (SD 5.1%). In the experimental group, the average glenoid version was 8.1° of retroversion (SD 5.0). The average humeral subluxation in the experimental group was 56% (SD 6.8%). Student t test revealed a statistically significant difference in glenoid version (P = .009) but not humeral subluxation (P = .25). Intra- and inter-rater reliability was measured by the intraclass correlation coefficient and found to have an excellent Fleiss rating with regard to both measurements. CONCLUSIONS: Glenoid retroversion is significantly increased in patients with symptomatic posterior labral tears compared with a control group. However, there was no statistically significant difference between the groups with regard to posterior humeral subluxation and, therefore, is not a reliable indicator of the presence or absence of symptomatic posterior shoulder instability. LEVEL OF EVIDENCE: Level III, retrospective comparative study.
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Luxaciones Articulares/diagnóstico por imagen , Inestabilidad de la Articulación/diagnóstico por imagen , Articulación del Hombro/diagnóstico por imagen , Adolescente , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Luxaciones Articulares/cirugía , Inestabilidad de la Articulación/cirugía , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estudios Retrospectivos , Articulación del Hombro/cirugía , Adulto JovenRESUMEN
BACKGROUND: This study assessed the accuracy of computed tomography (CT) arthrography when evaluating glenoid component stability in the setting of postarthroplasty shoulder pain. METHODS: We retrospectively reviewed all patients presenting to the clinic during a 5.5-year period to identify those with a painful shoulder arthroplasty more than 1 year after the index procedure. We excluded reverse and hemiarthroplasty procedures, patients with a clearly identifiable cause for pain, such as rotator cuff insufficiency or gross component loosening as seen on plain radiographs, and those with culture-positive aspiration. There were 14 patients with suspected glenoid component loosening but inconclusive plain radiographs. Each of the 14 patients underwent a CT arthrogram that was evaluated by the senior author (J.J.P.W.) for the presence or absence of contrast material underneath the polyethylene component. Operative reports and surgical videos from subsequent arthroscopy were reviewed to assess glenoid component stability as determined by direct arthroscopic visualization. RESULTS: CT arthrography suggested glenoid component loosening in 8 of 14 patients (57.1%), and arthroscopic inspection identified loosening in 10 of 14 patients (71.4%). In 3 of 10 patients (30%), CTA suggested a well-fixed glenoid component, but gross loosening was identified during arthroscopy. In this study, CTA yielded a sensitivity of 70%, a specificity of 75%, a positive predictive value of 87.5%, and a negative predictive value of 50.0%. CONCLUSION: CTA had a low negative predictive value (50%), and therefore, the prediction of component stability based on the absence of contrast between the glenoid component and the bone-cement interface does not always reflect true stability.
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Artrografía/métodos , Prótesis Articulares , Dimensión del Dolor , Articulación del Hombro/cirugía , Artroplastia de Reemplazo/efectos adversos , Artroplastia de Reemplazo/métodos , Humanos , Dolor Postoperatorio/etiología , Falla de Prótesis , Reoperación , Estudios Retrospectivos , Sensibilidad y Especificidad , Articulación del Hombro/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
We compared muscle activity of the quadriceps, hamstring, and gastrocnemius muscles when ACL-intact (ACL(INT)) and ACL-reconstructed (ACL(REC)) male and female subjects performed a jump-cut task. Surface electromyography sensors were used to evaluate time to peak muscle activity and muscle activity ratios. Rectus femoris (RF) and vastus medialis (VM) peak timing was 71 and 78 ms earlier in ACL(INT) than in ACL(REC) subjects, respectively. Biceps femoris (BF) peak timing was 90 ms earlier in ACL(INT) than in ACL(REC) subjects and 75 ms earlier in females than in males. Medial gastrocnemius (MG) muscle peak timing was 77 ms earlier in ACL(INT) than in ACL(REC) subjects. Lateral gastrocnemius (LG) and MG muscle peak times were 106 ms and 87 ms earlier in females than in males, respectively. The RF, VM, BF, and MG peaked later in ACL(REC) than in ACL(INT) subjects. There was evidence suggesting that the loading phase quadriceps:hamstring (quad:ham) muscle activity ratio was greater in ACL(REC) than in ACL(INT) subjects. Finally, the injury risk phase quad:ham muscle activity ratio was 4.8 times greater in females than in males. In conclusion, differences exist in muscle activity related to ACL status and sex that could potentially help explain graft failure risk and the sex bias.
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Reconstrucción del Ligamento Cruzado Anterior , Extremidad Inferior/fisiología , Músculo Esquelético/fisiología , Adulto , Electromiografía , Ejercicio Físico , Femenino , Humanos , Masculino , Caracteres SexualesRESUMEN
Secondary (AA) amyloidosis is a multisystem disorder complicating chronic infections or inflammatory diseases. It is characterized by extracellular deposit of fibrils composed of fragments of serum amyloid A (SAA), an acute phase reactant protein. The kidney is the most frequent organ involved, manifesting as progressive proteinuria and renal impairment. Attenuation of the level of circulating SAA protein by treating the underlying inflammatory condition remains the primary strategy in treating AA amyloidosis. However, at times, achieving adequate control of protein production can prove difficult. In addition, relapse of renal function often occurs rapidly following any subsequent inflammatory stimulus in patients with existing amyloidosis. Recently there has been an interest in finding other potential strategies targeting amyloid deposits themselves. Eprodisate is a sulfonated molecule with a structure similar to heparan sulfate. It competitively binds to the glycosaminoglycan-binding sites on SAA and inhibits fibril polymerization and amyloid deposition. Recent randomized clinical trial showed that it may slow down progressive renal failure in patients with AA amyloidosis. However confirmatory studies are needed and results of a second Phase III study are eagerly awaited to clarify whether or not eprodisate has a place in treating renal amyloid disease.