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1.
J Am Heart Assoc ; 13(20): e034690, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39377211

RESUMO

BACKGROUND: Long-QT syndrome is a primary cardiac ion channelopathy predisposing a patient to ventricular arrhythmia through delayed repolarization on the resting ECG. We aimed to establish a patient-specific, human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes model of long-QT syndrome type 3 (LQT3) using clustered regularly interspaced palindromic repeats (CRISPR/Cas9), for disease modeling and drug challenge. METHODS AND RESULTS: HiPSCs were generated from a patient with LQT3 harboring an SCN5A pathogenic variant (c.1231G>A; p.Val411Met), and an unrelated healthy control. The same SCN5A pathogenic variant was engineered into the background healthy control hiPSCs via CRISPR/Cas9 gene editing to generate a second disease model of LQT3 for comparison with an isogenic control. All 3 hiPSC lines were differentiated into cardiomyocytes. Both the patient-derived LQT3 (SCN5A+/-) and genetically engineered LQT3 (SCN5A+/-) hiPSC-derived cardiomyocytes showed significantly prolonged cardiomyocyte repolarization compared with the healthy control. Mexiletine, a cardiac voltage-gated sodium channel (NaV1.5) blocker, shortened repolarization in both patient-derived LQT3 and genetically engineered LQT3 hiPSC-derived cardiomyocytes, but had no effect in the control. Notably, calcium channel blockers nifedipine and verapamil showed a dose-dependent shortening of repolarization, rescuing the phenotype. Additionally, therapeutic drugs known to prolong the corrected QT in humans (ondansetron, clarithromycin, and sotalol) demonstrated this effect in vitro, but the LQT3 clones were not more disproportionately affected compared with the control. CONCLUSIONS: We demonstrated that patient-derived and genetically engineered LQT3 hiPSC-derived cardiomyocytes faithfully recapitulate pathologic characteristics of LQT3. The clinical significance of such an in vitro model is in the exploration of novel therapeutic strategies, stratifying drug adverse reaction risk and potentially facilitating a more targeted, patient-specific approach in high-risk patients with LQT3.


Assuntos
Potenciais de Ação , Células-Tronco Pluripotentes Induzidas , Síndrome do QT Longo , Miócitos Cardíacos , Canal de Sódio Disparado por Voltagem NAV1.5 , Humanos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Síndrome do QT Longo/genética , Síndrome do QT Longo/fisiopatologia , Síndrome do QT Longo/tratamento farmacológico , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Canal de Sódio Disparado por Voltagem NAV1.5/genética , Canal de Sódio Disparado por Voltagem NAV1.5/metabolismo , Antiarrítmicos/farmacologia , Mexiletina/farmacologia , Fenótipo , Edição de Genes/métodos , Sistemas CRISPR-Cas , Diferenciação Celular , Masculino , Bloqueadores dos Canais de Cálcio/farmacologia , Estudos de Casos e Controles , Doença do Sistema de Condução Cardíaco
2.
JSES Rev Rep Tech ; 4(4): 779-782, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39474164

RESUMO

Background: The partial pectoralis major transfer for the treatment of serratus anterior deficiency and modified Eden-Lange/Triple Tendon Transfer for trapezius deficiency result in improvement in pain and shoulder function. However, athletic function following these procedures is unknown. The purpose of this study is to determine the outcomes and return to military duty and athletic tasks following partial pectoralis major transfer and Tripler Tendon Transfer. Methods: A retrospective review of prospectively gathered data was performed for all patients surgically treated for medial and lateral scapular winging at two military medical centers. Preoperative patient-reported outcomes collected included the Single Assessment Numeric Evaluation (SANE), Visual Analog Scale (VAS), and American Shoulder and Elbow Surgeons (ASES). Patients were excluded if they had less than 1 year follow-up, no postoperative patient-reported outcomes or return to military duty data. Results: Eleven patients were surgically treated for scapular winging, 7 patients for serratus anterior deficiency and 4 patients for trapezius deficiency and were available for follow-up at a mean of 28 months. The mean preoperative outcome scores were SANE 40.9%, VAS 4.4 and ASES 54.4. Significant improvement in SANE 77.4% (P = .001), VAS 1.8 (P = .017) and ASES 75.7 (P = .008) was identified. Five of the 9 (55.6%) active-duty service members were able to meet their fitness requirements and remain on active-duty status. Conclusion: The split pectoralis major transfer for serratus anterior deficiency and the Triple Tendon Transfer for trapezius deficiency are excellent treatment options in patients who have high physical demands.

4.
Clin Sports Med ; 43(4): 547-565, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39232565

RESUMO

The glenohumeral joint is the least congruent and least constrained joint with a complex relationship of static and dynamic stabilizers to balance its native mobility with functional stability. In the young athlete, anterior shoulder instability is multifactorial and can be a challenge to treat, requiring a patient-specific treatment approach. Surgical decision-making must consider patient-specific factors such as age, sport activity and level, underlying ligamentous laxity, and goals for return to activity, in addition to careful scrutiny of the underlying pathology to include humeral and glenoid bone loss and surrounding scapular bone morphology.


Assuntos
Instabilidade Articular , Articulação do Ombro , Humanos , Instabilidade Articular/fisiopatologia , Articulação do Ombro/fisiopatologia , Articulação do Ombro/anatomia & histologia , Articulação do Ombro/fisiologia , Fenômenos Biomecânicos , Volta ao Esporte
5.
Eur Heart J Digit Health ; 5(4): 483-490, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39081948

RESUMO

Aims: Catheter ablation is a widely accepted intervention for atrial fibrillation (AF) management. Prior to undertaking this procedure, thorough patient education on its efficacy and potential complications is crucial. Additionally, educating patients about stroke risk management and anticoagulant therapy is imperative. At Mater Private Hospital in Dublin, we implemented a solution, integrating a customized treatment pathway and a mobile application. This patient-centred approach aims to optimize the clinical management of AF catheter ablation candidates, focusing on knowledge gaps and adherence to guideline-based care to enhance overall outcomes. Methods and results: The application automates pre-operative assessments and post-operative support, facilitating seamless patient-clinician communication. During the observation period (September 2022-April 2023), 63 patients installed the app. Patient adherence to the pathway was strong, with 98% of patients actively engaging in the treatment pathway and with 81% completing all pre-operative tasks. The average enrolment-to-admission duration was 14 days, and post-ablation tasks were fulfilled by 62% of patients within an average of 36 days. Operators perceived the solution as user-friendly and effective in enhancing patient connectivity. Patient satisfaction was high, and knowledge about AF improved notably through the solution, particularly concerning the recognition of symptoms and anticoagulation therapy-related complications. Conclusion: Our findings demonstrate the successful implementation of the app-based Ablation Solution, showcasing widespread patient use, improved adherence, and enhanced understanding of AF and its treatments. The system effectively connects healthcare providers with patients, offering a promising approach to streamline AF catheter ablation management and improve patient outcomes.

6.
Am J Sports Med ; 52(7): 1719-1727, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38702960

RESUMO

BACKGROUND: The incremental biological changes in the synovial microenvironment of the shoulder in acute and chronic instability that may contribute to joint degeneration are poorly understood. Proteomic analysis of synovial fluid in patients with shoulder instability may improve our understanding of proteins that are shed into shoulder synovial fluid after an injury. HYPOTHESIS: Injury-specific factors such as the direction of instability and the severity of glenoid and humeral bone loss are associated with the proteome of synovial fluid in patients with shoulder instability. STUDY DESIGN: Descriptive laboratory study. METHODS: Synovial fluid lavage samples were compared between patients with anterior (n = 12) and posterior (n = 8) instability and those without instability (n = 5). Synovial proteins were identified with liquid chromatography-tandem mass spectrometry. Orthogonal validation of protein targets found to be significant on tandem mass spectrometry was performed in a separate set of prospective patients with Western blotting. Data were processed and analyzed, and P values were adjusted with the Benjamini-Hochberg method for multiple comparisons. RESULTS: A total of 25 patients were included. Tandem mass spectrometry identified 720 protein groups in synovial fluid of patients with shoulder instability. There were 4 synovial proteins that were significantly expressed in patients with anterior instability relative to posterior instability: periostin (POSTN) (adjusted P value = .03; log fold change [logFc] = 4.7), transforming growth factor beta-induced protein ig-h3 (adjusted P value = .05; logFc = 1.7), collagen type VI alpha-3 chain (adjusted P value = .04; logFc = 2.6), and coagulation factor V (adjusted P value = .04; logFc = -3.3). Among these targets, POSTN showed a moderate correlation with the Hill-Sachs lesion size (r = 0.7). Prospective validation with Western blotting confirmed a significantly higher level of POSTN in synovial fluid of patients with anterior instability (P = .00025; logFc = 5.1). CONCLUSION: Proteomic analysis enriched our understanding of proteins that were secreted into shoulder synovial fluid of patients with shoulder instability. The identification of POSTN, a proinflammatory catabolic protein involved with tissue remodeling and repair, as a significant target in anterior shoulder instability is a novel finding. Therefore, further study is warranted to determine the role that POSTN may play in the progression of bone loss and posttraumatic osteoarthritis. CLINICAL RELEVANCE: Proteomic analysis of synovial fluid in patients with shoulder instability improved our understanding of this abnormality after an injury.


Assuntos
Biomarcadores , Moléculas de Adesão Celular , Instabilidade Articular , Proteômica , Líquido Sinovial , Humanos , Líquido Sinovial/metabolismo , Líquido Sinovial/química , Instabilidade Articular/metabolismo , Feminino , Biomarcadores/metabolismo , Biomarcadores/análise , Masculino , Moléculas de Adesão Celular/metabolismo , Moléculas de Adesão Celular/análise , Adulto , Adulto Jovem , Articulação do Ombro/metabolismo , Adolescente , Espectrometria de Massas em Tandem , Periostina
7.
J Am Acad Orthop Surg ; 32(11): 485-493, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38652884

RESUMO

A biorepository, also referred to as a "biobank," is a collection of biologic samples that are stored for laboratory research. With the emergence of precision medicine, the importance of leveraging individual patient biomolecular signatures to improve diagnosis, prognosis, and treatment is becoming increasingly recognized. Successful development and sustainment of a biorepository provides the potential for transformative preclinical research. Establishing a biobank requires a team approach with involvement of the institutions' research laboratory team and regulatory body. Execution of research activities requires a coordinated team approach for case identification, consent process, data and specimen collection, specimen processing, and storage and archiving. The advancing fields of precision medicine and orthobiologics provide incredible opportunities for institutions to generate novel lines of inquiry in musculoskeletal diseases through a multiomics approach (genomic, transcriptomic, proteomic, microbiomic). In addition, a biobank is an important component of post-market surveillance for the rapidly emerging field of orthobiologics.


Assuntos
Bancos de Espécimes Biológicos , Doenças Musculoesqueléticas , Manejo de Espécimes , Humanos , Doenças Musculoesqueléticas/terapia , Medicina de Precisão , Pesquisa Biomédica
8.
J Innov Card Rhythm Manag ; 15(3): 5813-5818, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38584745

RESUMO

The pathogenesis of inappropriate sinus tachycardia is not well understood, and the symptoms of inappropriate sinus tachycardia can be difficult to manage. Here, we present a case of inappropriate sinus tachycardia refractory to medical therapy and discuss our approach to sinus node modification by catheter ablation.

9.
Ir J Med Sci ; 193(4): 1775-1785, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38489124

RESUMO

BACKGROUND: Inherited cardiomyopathies (HCM, DCM, ACM) and cardiac ion channelopathies (long QT/Brugada syndromes, CPVT) are associated with significant morbidity and mortality; however, diagnosis of a familial pathogenic variant in a proband allows for subsequent cascade screening of their at-risk relatives. AIMS: We investigated the diagnostic yield from cardiac gene panel testing and reviewed variants of uncertain significance from patients attending three specialist cardiogenetics services in Ireland in the years 2002 to 2020. RESULTS: Reviewing molecular genetic diagnostic reports of 834 patients from 820 families, the initial diagnostic yield of pathogenic/likely pathogenic variants was 237/834 patients (28.4%), increasing to 276/834 patients (33.1%) following re-evaluation of cases with variant(s) of uncertain significance. Altogether, 42/85 patients with VUS reviewed (49.4%) had a re-classification that could change their clinical management. Females were more likely to carry pathogenic/likely pathogenic variants than males (139/374, 37.2% vs 137/460, 29.8%, respectively, p = 0.03), and the diagnostic yields were highest in the 0 to < 2 years age group (6/12, 50.0%) and amongst those tested for cardiomyopathy gene panels (13/35, 37.1%). Variants in the MYBPC3/MYH7 (87/109, 79.8%) and KCNQ1/KCNH2 (91/100, 91.0%) genes were the predominant genetic causes for hypertrophic cardiomyopathy and long QT syndrome, respectively. CONCLUSION: Our study highlights the importance of collation and review of pre-ACMG genetic variants to increase diagnostic utility of genetic testing for inherited heart disease. Almost half of patients with pre-ACMG VUS reviewed had their variant re-classified to likely pathogenic/likely benign which resulted in a positive clinical impact for patients and their families.


Assuntos
Testes Genéticos , Humanos , Feminino , Masculino , Testes Genéticos/métodos , Testes Genéticos/estatística & dados numéricos , Adulto , Adolescente , Criança , Lactente , Pré-Escolar , Pessoa de Meia-Idade , Irlanda , Adulto Jovem , Recém-Nascido , Miosinas Cardíacas/genética , Idoso , Cardiomiopatias/genética , Cardiomiopatias/diagnóstico
10.
Circ Genom Precis Med ; 17(2): e004404, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38353104

RESUMO

BACKGROUND: Less than 40% of patients with dilated cardiomyopathy (DCM) have a pathogenic/likely pathogenic genetic variant identified. TBX20 has been linked to congenital heart defects; although an association with left ventricular noncompaction (LVNC) and DCM has been proposed, it is still considered a gene with limited evidence for these phenotypes. This study sought to investigate the association between the TBX20 truncating variant (TBX20tv) and DCM/LVNC. METHODS: TBX20 was sequenced by next-generation sequencing in 7463 unrelated probands with a diagnosis of DCM or LVNC, 22 773 probands of an internal comparison group (hypertrophic cardiomyopathy, channelopathies, or aortic diseases), and 124 098 external controls (individuals from the gnomAD database). Enrichment of TBX20tv in DCM/LVNC was calculated, cosegregation was determined in selected families, and clinical characteristics and outcomes were analyzed in carriers. RESULTS: TBX20tv was enriched in DCM/LVNC (24/7463; 0.32%) compared with internal (1/22 773; 0.004%) and external comparison groups (4/124 098; 0.003%), with odds ratios of 73.23 (95% CI, 9.90-541.45; P<0.0001) and 99.76 (95% CI, 34.60-287.62; P<0.0001), respectively. TBX20tv was cosegregated with DCM/LVNC phenotype in 21 families for a combined logarythm of the odds score of 4.53 (strong linkage). Among 57 individuals with TBX20tv (49.1% men; mean age, 35.9±20.8 years), 41 (71.9%) exhibited DCM/LVNC, of whom 14 (34.1%) had also congenital heart defects. After a median follow-up of 6.9 (95% CI, 25-75:3.6-14.5) years, 9.7% of patients with DCM/LVNC had end-stage heart failure events and 4.8% experienced malignant ventricular arrhythmias. CONCLUSIONS: TBX20tv is associated with DCM/LVNC; congenital heart defect is also present in around one-third of cases. TBX20tv-associated DCM/LVNC is characterized by a nonaggressive phenotype, with a low incidence of major cardiovascular events. TBX20 should be considered a definitive gene for DCM and LVNC and routinely included in genetic testing panels for these phenotypes.


Assuntos
Cardiomiopatia Dilatada , Cardiopatias Congênitas , Masculino , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Feminino , Cardiomiopatia Dilatada/patologia , Cardiopatias Congênitas/genética , Arritmias Cardíacas , Fenótipo , Proteínas com Domínio T/genética
11.
J Med Genet ; 61(5): 423-427, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38160043

RESUMO

Formin homology 2 domain-containing 3 (FHOD3) gene has emerged as one of the main non-sarcomeric genes associated with hypertrophic cardiomyopathy (HCM), but no cases of biallelic variants associated with disease have been described to date. From 2014 until 2021, FHOD3 was evaluated in our center by next-generation sequencing in 22 806 consecutive unrelated probands. The p.Arg637Gln variant in FHOD3 was enriched in our HCM cohort (284 of 9668 probands; 2.94%) compared with internal controls (64 of 11 480; 0.59%) and gnomAD controls (373 of 64 409; 0.58%), with ORs of 5.40 (95% CI: 4.11 to 7.09) and 5.19 (95% CI: 4.44 to 6.07). The variant affects a highly conserved residue localised in a supercoiled alpha helix considered a clustering site for HCM variants, and in heterozygosis can act as a predisposing factor (intermediate-effect variant) for HCM, with an estimated penetrance of around 1%. Additionally, seven homozygous carriers of p.Arg637Gln in FHOD3 were identified. All but one (unaffected) showed an early presentation and a severe HCM phenotype. All this information suggest that p.Arg637Gln variant in FHOD3 is a low-penetrant variant, with an intermediate effect, that contributes to the development of HCM in simple heterozygosis, being associated with a more severe phenotype in homozygous carriers.


Assuntos
Cardiomiopatia Hipertrófica , Humanos , Cardiomiopatia Hipertrófica/genética , Fenótipo , Homozigoto , Penetrância , Heterozigoto , Forminas/genética
12.
J Clin Med ; 12(17)2023 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-37685701

RESUMO

Uncontrolled arterial hypertension is a major global health issue. Catheter-based renal denervation has shown to lower blood pressure in sham-controlled trials and represents a device-based, complementary treatment option for hypertension. In this situation assessment, the authors, who are practicing experts in hypertension, nephrology, general practice and cardiology in the Republic of Ireland, discuss the current evidence base for the BP-lowering efficacy and safety of catheter-based renal denervation with different modalities. Although important questions remain regarding the identification of responders, and long-term efficacy and safety of the intervention, renal denervation has the potential to provide much-needed help to address hypertension and its adverse consequences. The therapeutic approach needs to be multidisciplinary and personalised to take into account the perspective of patients and healthcare professionals in a shared decision-making process.

13.
JSES Int ; 7(5): 737-742, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37719809

RESUMO

Background: Prior evidence has identified specific posterior acromial morphology as significantly associated with unidirectional posterior shoulder instability. The purpose of this study is to determine the influence of posterior acromial morphology on the outcomes of arthroscopic posterior capsulolabral repair (APCLR) for unidirectional posterior shoulder instability. Additionally, we sought to determine the influence of posterior acromial morphology on the rate and time to return to pushups following APCLR. Methods: We performed a retrospective review of prospectively collected data. The study included consecutive patients undergoing APCLR. Data collected included demographics, radiographic measurements including posterior acromial height (PAH) and posterior acromial tilt on preoperative scapular-Y radiographs, and patient-reported outcome measures at the preoperative and postoperative visits. In addition, starting at 6 months postoperative, patients were asked if they could perform pushups defined as at least 10 repetitions. At the final follow-up, we collected the number of pushups patients were able to perform. Results: Thirty-two consecutive patients underwent APCLR with a mean follow-up of 26 months (range, 12-41). Significant improvement from preoperative to 2 years postoperative was demonstrated in Subjective Shoulder Value (50-85), VAS (6-2.5), American Shoulder and Elbow Surgeons (48 to 83), and Western Ontario Shoulder Instability (WOSI) (1437-777), P = .001. The recurrent instability rate was 3/32 (9%). Patients with PAH > 23 (N = 17) had a recurrent instability rate of 18% (3/17) versus PAH ≤ 23 (N = 15) 0% (0/15), worse WOSI scores (P = .41), and a lower number of pushups (P = .48). The percentage of patients reporting the ability to perform pushups was (6 months/1 year/2 years) (50%/78%/95%). The mean number of pushups reported at the final follow-up was 33 (range, 1-60). Discussion: Following APCLR, approximately 50% of patients resume pushups at 6 months postoperatively, and 80% return at 1 year. Patients reported performing a mean of 33 pushups following APCLR at the final follow-up. Patients with a PAH greater than 23 on preoperative scapular-Y radiographs had a higher rate of recurrent posterior instability, worse WOSI scores, and lower return to pushups; however, the results did not meet statistical significance. Therefore, future larger studies are needed to determine if posterior acromial morphology is independently associated with worse outcomes and increased recurrent instability rates following APCLR.

14.
Arthrosc Tech ; 12(7): e1115-e1119, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37533900

RESUMO

Arthroscopic shoulder surgery can be performed for retrieval of bullets and retained metallic fragments in the glenohumeral and subacromial spaces. Previous case reports and case series have demonstrated the effectiveness of an arthroscopic approach over an open procedure, as it is less invasive, allows for improved inspection and documentation of the joint surfaces and periarticular structures, and potentially leads to a faster recovery. An arthroscopic approach for extracting foreign bodies from both the quadrilateral space and the posterior extra-articular space by first accessing the glenohumeral space has yet to be described. This inside-out technique may afford surgeons the potential for improved visualization and less morbidity compared with a traditional open posterior approach. We report a technique for an arthroscopic inside-out approach for removal of extra-articular foreign bodies retained in either the quadrilateral space or the posterior extra-articular space.

15.
Cardiol Res ; 14(4): 268-278, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37559712

RESUMO

Background: Low voltage areas (LVAs) have been proposed as surrogate markers for left atrial (LA) scar. Correlation between voltages in sinus rhythm (SR) and atrial fibrillation (AF) have previously been measured via point-by-point analysis. We sought to compare LA voltage composition measured in SR to AF, utilizing a high-density automated voltage histogram analysis (VHA) tool in those undergoing pulmonary vein isolation (PVI) for persistent AF (PeAF). Methods: We retrospectively analyzed patients with PeAF undergoing de novo PVI. Maps required ≥ 1,000 voltage points in each rhythm and had a standardized procedure (mapped in AF then remapped in SR post-PVI). We created six anatomical segments (AS) from each map: anterior, posterior, roof, floor, septal and lateral AS. These were analyzed by VHA, categorizing atrial LVAs into 10 voltage aliquots 0 - 0.5 mV. Data were analyzed using SPSS v.26. Results: We acquired 58,342 voltage points (n = 10 patients, mean age: 67 ± 13 years, three females). LVA burdens of ≤ 0.2 mV, designated as "severe LVAs", were comparable between most AS (except on the posterior wall) with good correlation. Mapped voltages between the ranges of 0.21 and 0.5 mV were labeled as "diseased LA tissue", and these were found significantly more in AF than SR. Significant differences were seen on the roof, anterior, posterior, and lateral AS. Conclusions: Diseased LA tissue (0.21 - 0.5 mV) burden is significantly higher in AF than SR, mainly in the anterior, roof, lateral, and posterior wall. LA "severe LVA" (≤ 0.2 mV) burden is comparable in both rhythms, except with respect to the posterior wall. Our findings suggest that mapping rhythm has less effect on the LA with voltages < 0.2 mV than 0.2 - 0.5 mV across all anatomical regions, excluding the posterior wall.

16.
Arthrosc Sports Med Rehabil ; 5(5): 100770, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37560142

RESUMO

Purpose: To determine the percentage of patients who report the ability to run 1 mile at various time points after arthroscopic and open shoulder surgery. Methods: We performed a retrospective review of prospectively collected data for all active-duty military patients aged 18 to 45 years who underwent shoulder surgery at a single institution over a 2-year period. The rehabilitation protocol discouraged running before 3 months, but all patients were able to return to unrestricted running at 3 months postoperatively. Patients were excluded if they lacked 1-year follow-up data. Parameters collected included demographic information and validated patient-reported outcome measures at the preoperative and short-term postoperative visits, as well as patients' ability to run at least 1 mile postoperatively. Results: A total of 126 patients were identified who underwent shoulder surgery with return-to-running data. Compared with baseline, significant improvements in patient-reported outcomes were shown at 1 and 2 years postoperatively (P = .001). The percentage of patients reporting the ability to run 1 mile postoperatively was 59% at 3 months, 74% at 4.5 months, 79% at 6 months, 83% at 12 months, and 91% at 24 months. There was no significant difference in patients undergoing shoulder surgery for instability versus non-instability diagnoses or in patients undergoing open versus arthroscopic anterior stabilization. All 11 patients unable to return to running at final follow-up had chronic lower-extremity diagnoses limiting their running ability. Conclusions: Young military athletes undergoing arthroscopic and open shoulder surgery have a high rate of early return to running. Approximately 60% of patients report the ability to run 1 mile at 3 months postoperatively, and three-quarters of patients do so at 4.5 months. Age, sex, military occupation, underlying diagnosis or type of surgery did not influence the rate of return to running after shoulder surgery. Level of Evidence: Level IV, therapeutic case series.

17.
Stem Cell Rev Rep ; 19(8): 2774-2789, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37653182

RESUMO

Human induced pluripotent stem cells (hiPSCs) have been widely used in cardiac disease modelling, drug discovery, and regenerative medicine as they can be differentiated into patient-specific cardiomyocytes. Long QT syndrome type 3 (LQT3) is one of the more malignant congenital long QT syndrome (LQTS) variants with an SCN5A gain-of-function effect on the gated sodium channel. Moreover, the predominant pathogenic variants in LQTS genes are single nucleotide substitutions (missense) and small insertion/deletions (INDEL). CRISPR/Cas9 genome editing has been utilised to create isogenic hiPSCs to control for an identical genetic background and to isolate the pathogenicity of a single nucleotide change. In this study, we described an optimized and rapid protocol to introduce a heterozygous LQT3-specific variant into healthy control hiPSCs using ribonucleoprotein (RNP) and single-stranded oligonucleotide (ssODN). Based on this protocol, we successfully screened hiPSCs carrying a heterozygous LQT3 pathogenic variant (SCN5A±) with high efficiency (6 out of 69) and confirmed no off-target effect, normal karyotype, high alkaline phosphatase activity, unaffected pluripotency, and in vitro embryonic body formation capacity within 2 weeks. In addition, we also provide protocols to robustly differentiate hiPSCs into cardiomyocytes and evaluate the electrophysiological characteristics using Multi-electrode Array. This protocol is also applicable to introduce and/or correct other disease-specific variants into hiPSCs for future pharmacological screening and gene therapeutic development.


Assuntos
Células-Tronco Pluripotentes Induzidas , Síndrome do QT Longo , Humanos , Nucleotídeos , Sistemas CRISPR-Cas/genética , Síndrome do QT Longo/genética
18.
Arthrosc Sports Med Rehabil ; 5(4): 100777, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37520505

RESUMO

Purpose: The purposes of this study were to use computed tomography (CT) scans to compare the radius of curvature (ROC) of the inferior concave surface of the distal clavicle to the glenoid, determine graft dimensions, and compare the ROC of the congruent-arc distal clavicle autograft (DCA) to the congruent-arc Latarjet graft. Methods: Patients who underwent bony glenoid reconstruction via a Laterjet procedure between January 2018 and January 2023 at a single institution were retrospectively identified. CT scans were used to measure the ROC of the glenoid on the axial and coronal sequences, measure the ROC of the distal clavicle on the sagittal oblique sequences, and determine the dimensions of the distal clavicle and coracoid graft. Results: A total of 42 patients were included (Latarjet, n = 22; control, n = 20). The mean ROC of the inferior surface of the distal clavicle was not significantly different from the ROC of the glenoid in the coronal (P = .15) or axial planes (P = .65). The ROC of the coracoid when measured in the sagittal plane was not significantly different from the ROC of the distal clavicle (P = .25). The length, depth, and surface area of the coracoid in the congruent arc orientation were significantly larger than the distal clavicle (P < .005). Patients in the control group tended to have both a larger inferior clavicle ROC and a larger coracoid ROC compared to the Latarjet group (32.8 mm vs 29.6 mm, P < .0001; 31.8 mm vs 30.9 mm, P = .02). Conclusions: The ROC of the inferior distal clavicle is similar to that of the glenoid in both the axial and coronal planes and similar to the inferior coracoid. Clinical Relevance: CT analysis reveals that the congruent-arc DCA technique provides a robust graft with dimensions that are suitable for reconstruction of the anterior glenoid.

19.
JSES Int ; 7(4): 668-672, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37426921

RESUMO

Background: The purpose of this study is to utilize elbow magnetic resonance imaging (MRI) to compare the radius of curvature (ROC) of the radial head peripheral cartilaginous rim and the cartilage contour of the capitellum to evaluate if the radial head could be a suitable osteochondral autograft for capitellar pathology. Methods: All patients who underwent an MRI of the elbow over a three-year period were reviewed. Patients with the following diagnoses were excluded: osteochondritis dissecans, osteomyelitis, tumor, and osteoarthritis. The radius of curvature of the radial head (RhROC) was measured on the axial oblique MRI sequence. The radius of curvature of the capitellum (CapROC) was measured on sagittal oblique MRI sequences, the width of the articular surface of the capitellum on coronal MRI sequences and the radial head height (RhH) and capitellar vertical height on sagittal oblique sequences. All measurements were obtained at the midpoint of the radiocapitellar joint. Spearman's coefficient was used to assess the correlation between ROC measurements. Results: Eighty-three patients were included with a mean age of 43 +/- 17 years (57 males and 26 females, 51 right and 32 left elbows). The median RhROC and CapROC measurements were 12.3 mm (interquartile range [IQR] 1.6) and 11.9 mm (IQR 1.7), respectively. The median difference was 0.3 mm (IQR = 0.6; CI 95% = [0.24, 0.46]; P < .001). A strong positive correlation was found between RhROC and CapROC (ρ = 0.89; r2 = 0.819; P < .001). Ninety-four percent (78/83) of patients had a median difference between the RhROC and CapROC of less than or equal to 1 mm, and 63% (52/83) were within 0.5 mm. The inter-rater and intra-rater reliability for RhROC and CapROC was good, intraclass correlation coefficient (ICC) = 0.89, ICC = 0.87, and ICC = 0.96, ICC = 0.97, respectively. RhH was 10.6 ± 1.3 mm, and the width of the articular surface of the capitellum was found to be 13.8 ± 1.6 mm. Conclusion: The ROC of the convex peripheral cartilaginous rim of the radial head is similar to the ROC of the capitellum. In addition, the RhH was approximately 78% of the capitellar articular width. Based on this imaging analysis, the radial head could prove to be a robust local osteochondral autograft with a similar cartilage contour in the reconstruction of the capitellum in complex intra-articular distal humerus fractures with associated radial head fractures and in the setting of "kissing lesions" of the radiocapitellar joint. Furthermore, an osteochondral plug harvested from the "safe zone" of the peripheral cartilaginous rim of the radial head could be utilized to treat isolated osteochondral lesions of the capitellum.

20.
Arthrosc Sports Med Rehabil ; 5(3): e725-e730, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37388891

RESUMO

Purpose: To compare failure rates and clinical outcomes after hamstring autograft anterior cruciate ligament (ACL) reconstruction with and without allograft augmentation by a single surgeon otherwise using the same surgical technique. Methods: This was a retrospective analysis with prospectively collected patient-reported outcomes of primary hamstring autograft ACL reconstruction with and without allograft augmentation performed in a military population by a single surgeon. The primary outcome measure was graft failure, defined as graft rupture confirmed by use of magnetic resonance imaging scans and/or revision ACL reconstruction. The secondary outcome measure was the postoperative Knee Injury and Osteoarthritis Outcome Score. Results: This study included 112 patients with a mean follow-up period of 65.3 months. In patients with a graft diameter of 8 mm or greater, there was no difference in failure rates (9.4% for autograft only vs 6.3% for hybrid, P = .59). There was a higher failure rate in patients in the autograft-only group with a graft diameter of less than 8 mm (29.4%) when compared with the hybrid graft group (6.3%, P = .008). There were no hybrid grafts less than 8 mm in diameter. There were no differences in the Knee Injury and Osteoarthritis Outcome Score between groups as long as the graft diameter was 8 mm or greater. Conclusions: In patients undergoing hamstring ACL reconstruction, there was no significant difference in graft failure rates or outcome scores between autograft only and autograft with allograft augmentation as long as grafts were 8 mm or greater. High failure rates were seen when the graft diameter was less than 8 mm. Level of Evidence: Level III, retrospective cohort study.

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