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1.
Artigo em Inglês | MEDLINE | ID: mdl-38960139

RESUMO

BACKGROUND: Acute unreconstructible 3- or 4-part proximal humerus fractures can be treated with hemiarthroplasty or reverse polarity shoulder arthroplasty. Randomized trials using implants from multiple different companies or uncemented implants have found superior results with reverse polarity arthroplasty. AIMS: This study aims to determine whether cemented reverse polarity arthroplasty produces a superior outcome compared to cemented hemiarthroplasty using one implant system in patients aged 65 years and over at 12 months follow-up as measured with the Constant score. METHODS: A prospective patient and assessor blinded multicenter randomized controlled trial was conducted of shoulder hemiarthroplasty or reverse polarity arthroplasty in patients aged 65 years and older with acute 3- and 4-part proximal humerus fracture not amenable to osteosynthesis. The primary outcome was the Constant score at 12 months with total follow-up to 24 months. Block randomization by site was undertaken using random number generation and sealed envelopes. Power analysis indicated that 17 patients were required in each arm to achieve 80% power with an alpha-value of 5%. Secondary outcome measures were the difference in the mean Constant Score, Quick Disabilities of the Arm Shoulder and Hand Questionnaire (QuickDASH), Oxford Shoulder Score (OSS), American Shoulder and Elbow Surgeons (ASES) Score and EQ5D-5L up to two years; differences in complication rate at one and two years; differences in revision and implant failure at one and two years. RESULTS: 18 patients were randomized to hemiarthroplasty and 18 to reverse polarity arthroplasty across 4 sites. The primary outcome as measured by the Constant score at 12 months was better in the reverse polarity shoulder arthroplasty (RSA) group (Mean 51.1, s.d. 14.9) compared to the hemiarthroplasty (HA) group (mean 35.0, s.d. 13.5) (p=0.004). No significant difference was reported at 24 months but this may be due to high rates of attrition (22%). The mean EQ-5D-5L patient rated health status score was significantly higher in the RSA group compared to the HA group at 12 months. One hemiarthroplasty was revised due to implant uncoupling and one reverse polarity shoulder replacement was revised due to instability. No other complications were recorded. DISCUSSION: Treatment of unreconstructible 3- or 4-part proximal humerus fractures with reverse polarity shoulder arthroplasty results in a superior outcome compared to shoulder hemiarthroplasty at 12 months measured with the Constant score with no increased risk of failure up to 24 months in patients age 65 years and over. High attrition rates are observed in this older population due to cognitive decline and death from other causes.

2.
Contemp Clin Trials ; 131: 107268, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37321352

RESUMO

BACKGROUND: Suicide is a leading cause of death in adolescents and adults in the US. Follow-up support delivered when patients return home after an emergency department (ED) or primary care encounter can significantly reduce suicidal ideation and attempts. Two follow-up models to augment usual care including the Safety Planning Intervention have high efficacy: Instrumental Support Calls (ISC) and Caring Contacts (CC) two-way text messages, but they have never been compared to assess which works best. This protocol for the Suicide Prevention Among Recipients of Care (SPARC) Trial aims to determine which model is most effective for adolescents and adults with suicide risk. METHODS: The SPARC Trial is a pragmatic randomized controlled trial comparing the effectiveness of ISC versus CC. The sample includes 720 adolescents (12-17 years) and 790 adults (18+ years) who screen positive for suicide risk during an ED or primary care encounter. All participants receive usual care and are randomized 1:1 to ISC or CC. The state suicide hotline delivers both follow-up interventions. The trial is single-masked, with participants unaware of the alternative treatment, and is stratified by adolescents/adults. The primary outcome is suicidal ideation and behavior, measured using the Columbia Suicide Severity Rating Scale (C-SSRS) screener at 6 months. Secondary outcomes include C-SSRS at 12 months, and loneliness, return to crisis care for suicidality, and utilization of outpatient mental health services at 6 and 12 months. DISCUSSION: Directly comparing ISC and CC will determine which follow-up intervention is most effective for suicide prevention in adolescents and adults.


Assuntos
Suicídio , Envio de Mensagens de Texto , Adolescente , Adulto , Humanos , Serviço Hospitalar de Emergência , Atenção Primária à Saúde , Ideação Suicida , Suicídio/psicologia , Prevenção do Suicídio , Ensaios Clínicos Pragmáticos como Assunto
3.
J Shoulder Elbow Surg ; 32(10): 2017-2026, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37263477

RESUMO

BACKGROUND: The purpose of this study is to report the clinical and radiologic outcomes of patients undergoing primary or revision reverse total shoulder arthroplasty using custom 3D-printed components to manage severe glenoid bone loss with a minimum of 2-year follow-up. METHODS: Following ethical approval, patients were identified and invited to participate. Inclusion criteria were (1) severe glenoid bone loss necessitating the need for custom implants and (2) patients with definitive glenoid and humeral components implanted more than 2 years prior. Included patients underwent clinical assessment using the Oxford Shoulder Score (OSS), Constant-Murley score, American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES), and the quick Disabilities of the Arm, Shoulder, and Hand questionnaire (QuickDASH). Radiographic assessment included anteroposterior and axial projections. Patients were invited to attend a computed tomography (CT) scan to confirm osseointegration. Statistical analysis used descriptive statistics (mean and standard deviation [SD]) and paired t test for parametric data. RESULTS: Eleven patients declined to participate. Five patients were deceased prior to study commencement, leaving 42 remaining patients in this analysis. Three patients had revision surgery before the 2-year follow-up; of these, 2 retained their custom glenoid components. Mean follow-up was 31.6 months from surgery (range 24-52 months). All 4 scores improved: OSS from a mean 15 (SD 8.4) to 36 (SD 12) (P < .001), Constant-Murley score from a mean 15 (SD 11.2) to 52 (SD 20.1) (P < .001), QuickDASH from a mean 70 (SD 21) to 31 (SD 24.8) (P = .004), and the ASES score from a mean 22 (SD 17.8) to 71 (SD 23.3) (P = .007). Radiologic evaluation demonstrated good osseointegration in all but 1 included patient. CONCLUSION: The utility of custom 3D-printed components for managing severe glenoid bone loss in primary and revision reverse total shoulder arthroplasty yields significant clinical improvements in this complex cohort. Large complex glenoid bone defects can be managed successfully with custom 3D-printed glenoid components.


Assuntos
Artroplastia do Ombro , Cavidade Glenoide , Articulação do Ombro , Humanos , Artroplastia do Ombro/efeitos adversos , Articulação do Ombro/diagnóstico por imagem , Articulação do Ombro/cirurgia , Seguimentos , Resultado do Tratamento , Impressão Tridimensional , Estudos Retrospectivos , Cavidade Glenoide/diagnóstico por imagem , Cavidade Glenoide/cirurgia , Amplitude de Movimento Articular
4.
J Affect Disord ; 331: 442-451, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-36963515

RESUMO

BACKGROUND: Caring Contacts can effectively reduce suicide ideation, attempts, and death. In published clinical trials, Caring Contacts were sent by someone who knew the recipient. At scale, Caring Contacts programs rarely introduce the recipient and sender. It is not known whether receiving Caring Contacts from someone unknown is as effective as messages from someone the recipient has met. METHODS: Pragmatic randomized controlled trial comparing Caring Contacts with (CC+) versus without an introductory phone call (CC). Recruitment occurred January-July 2021, with outcomes assessed at 6 months. Participants were primary care patients or healthcare providers/staff reporting adverse mental health outcomes on a qualifying survey. Participants were sent 11 standardized caring text messages over 6 months; when participants replied, they received personalized unscripted responses. CC+ calls were semi-structured. The primary outcome was loneliness (NIH Toolkit). RESULTS: Participants included 331 patients (mean [SD] age: 45.5 [16.4], 78.9 % female) and 335 healthcare providers/staff (mean [SD] age: 40.9 [11.8], 86.6 % female). There were no significant differences in loneliness at 6 months by treatment arm in either stratum. In patients, mean (SD) loneliness was 61.9 (10.7) in CC, and 60.8 (10.3) in CC+, adjusted mean difference of -1.0 (95 % CI: -3.0, 1.0); p-value = 0.31. In providers/staff, mean (SD) loneliness was 61.2 (11) in CC, and 61.3 (11.1) in CC+, adjusted mean difference of 0.2 (95 % CI: -1.8, 2.2); p-value = 0.83. LIMITATIONS: Study population was 93 % white which may limit generalizability. CONCLUSIONS: Including an initial phone call added operational complexity without significantly improving the effectiveness of a Caring Contacts program.


Assuntos
Transtornos Mentais , Envio de Mensagens de Texto , Humanos , Feminino , Pessoa de Meia-Idade , Adulto , Masculino , Solidão , Ideação Suicida , Pessoal de Saúde
5.
Shoulder Elbow ; 14(3): 269-277, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35599713

RESUMO

Aims: Achieving purchase in native glenoid bone is essential for the stability of the glenoid baseplate when bone graft is used to address bone loss in both primary and revision shoulder arthroplasty procedures. The aim of this study is to assess the required depth of the baseplate peg in native bone when bone graft is used to result in satisfactory integration. Patients and methods: The CT scans of patients who underwent either primary or revision arthroplasty procedures with bone graft using the SMR Axioma Trabecular Titanium (TT) Metal Backed glenoid system were assessed. We measured the depth of the glenoid peg in native glenoid bone. Measurements were taken by two authors separately. Results: The scans of 53 patients (mean age 68 years) with a minimum follow-up of two years were reviewed. Implants included 12 anatomical and 41 reverse geometry prostheses. There were 17 primaries and 36 revisions: hemiarthroplasties (20) total (14) and reverse (2) implants. Bone grafts were from humeral head (15), iliac crest (34) and allograft (4). The mean depths were 8.8 mm (first assessor) and 9.10 mm (second assessor). The glenoid peg violated the glenoid vault in 32 patients and this did not adversely affect the outcome. There were three failures of implants all of which were aseptic failures and had peg penetration of less than 6 mm. Conclusions: The mean depth of glenoid peg in native bone was 9 mm (variation between 0.2 and 0.52 mm at 95% confidence interval). Aseptic loosening was seen with peg penetration less than 6 mm in native bone. Glenoid vault violation was not associated with loosening.

6.
Shoulder Elbow ; 13(6): 649-655, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34804214

RESUMO

BACKGROUND: Adhesive capsulitis (frozen shoulder) is characterised by pain and loss of range of motion of the glenohumeral joint. It can be present as primary (idiopathic) or secondary to surgery, trauma or other conditions that restrict the use of the shoulder joint. Various treatment options have been adopted including physiotherapy, manipulation under anaesthetic, hydrodilatation and arthroscopic or open capsular release but the optimal form of management remains uncertain. OBJECTIVES: The purpose of the study was to assess the clinical outcome of glenohumeral hydrodilatation in three cohorts of patients with different aetiologies with adhesive capsulitis. STUDY DESIGN & METHODS: We carried out a retrospective study of patient who underwent hydrodilatation for adhesive capsulitis between 2013 and 2015. The procedure was performed by a specialist musculoskeletal radiologist under radiological guidance. The injection consisted of steroids, local anaesthetics and NaCl solution with a target volume around 35 mL. Our outcome measures were range of motion, and pre- and post-operative pain. Patients were divided into three groups based on the presumed cause of their stiffness: idiopathic, post-traumatic and post-surgical. RESULTS: Two hundred fifty patients were included, with a mean age of 59 years (range: 20-79). Of these, 180 had idiopathic primary adhesive capsulitis (27 were diabetic), 23 were post-traumatic, and 20 following surgical procedures. Thirty-four required further intervention following initial hydrodilatation with 8 undergoing repeat hydrodilatation, and 26 requiring arthroscopic capsular release. The diabetic group accounted for 16 capsular releases and 4 repeat procedures, while the idiopathic group accounted for 9 and 4, respectively. One patient required capsular release in the surgical group. An improvement was recorded in ROM in all groups with mean abduction improving from 59° to 110°, flexion from 50° to 120° and external rotation from 20° to 50°. With regards to pain, the majority showed an improvement from severe or moderate pain to no or mild pain. CONCLUSIONS: Results show that hydrodilatation resulted in an improvement in all outcome measures, with only a small number of patients, especially those with diabetes, needing further procedures or showing no improvement in range of motion and pain. There was no difference between the post-traumatic and post-surgical groups.

7.
J Clin Orthop Trauma ; 19: 62-66, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34046301

RESUMO

BACKGROUND: Recent evidence continues to confirm the effectiveness of arthroscopic superior capsular reconstruction (SCR) in relieving pain and improving function in an irreparable cuff deficient shoulder. This paper presents an up-to-date literature review on SCRand a tertiary referral unit experience in the United Kingdom. METHODS: Data was prospectively collected on patients undergoing SCR for irreparable rotator cuff tears using a dermal allograft. Patients with already established arthritis were excluded. The first 49 consecutive cases performed by 3 surgeons over 3 years (including their learning curve) with average follow-up of 19 months (range 3-37 months) were analysed. The outcomes assessed were re-operation rates, patient satisfaction and complications. The study group was analysed to identify the factors predicting outcomes. RESULTS: The average age of the cohort was 56 years. The re-operation rate in this group was 12.2% with each of these 6 patients subsequently undergoing a reverse total shoulder arthroplasty. Forty (82%) patients were satisfied with the outcome of the procedure with 35 (72%) of them showing complete pain relief, 5 (10%) having dull aches and clicks and the remaining 9 (18%) unsatisfied due to pain. There was no difference in satisfaction rates between different age groups (p > 0.05). The pre-operative factors associated with poor outcomes included patients with multiple previous surgeries on the same shoulder (p = 0.02) and teres minor atrophy or tear (p = 0.03). The other factors that showed a trend towards inferior outcomes (but not statistically significant) included patients with degenerative tears, symptoms of longer duration (>24 months) and subscapularis tear/atrophy. No serious adverse effects such as graft rejection, infection or neuro-vascular injury were observed. CONCLUSION: Early results of superior capsular reconstruction are promising and may offer an answer to a challenging group of patients with symptomatic irreparable rotator cuff tears. It is likely that the relatively low re-operation rates can be further improved by considering the negative prognostic factors in defining indications for surgery.

9.
J Shoulder Elbow Surg ; 30(3): 668-678, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32650067

RESUMO

BACKGROUND: Severe glenoid bone loss remains a challenge in patients requiring shoulder arthroplasty and often requires autogenous bone grafting. The purpose of this study was to assess the integrity of the bone graft at 2 years in a series of primary and revision shoulder replacements where glenoid bone loss was managed using a structural autograft (humeral head or iliac crest bone graft) in combination with a trabecular titanium (TT) implant. METHODS: Ethical approval was sought, and the study has a portfolio study status by the NIHR (17/YH/0318). We contacted patients who had primary and revision shoulder arthroplasty with Lima Axioma TT metal-back glenoid with autologous bone graft and were more than 2 years since their operation. All eligible patients underwent computed tomographic evaluation, clinical review, and scoring. Early failures of composite fixation and patients who had revision procedures were excluded (2 patients). RESULTS: Forty-one patients (43 shoulders) with a mean age of 65 years (range 33-85 years) were reviewed. There were 24 women and 17 men. The average follow-up period was 40 months (range 24-59 months). Primary arthroplasty was performed in 24 shoulders, whereas 19 shoulders had revision arthroplasty. Twenty-five shoulders had reverse shoulder replacement and 18 had anatomic shoulder replacement. Twenty-four shoulders had graft taken from the humeral head, and 19 had iliac crest bone graft, reflecting the number of revisions. We used Wrightington classification for porous metal implant and bone graft incorporation. Satisfactory bone graft incorporation (>50%) was seen in 40 shoulders, and only 3 patients had <50% graft incorporation. The scans at 2 years or later showed no significant deterioration in the bone graft from the early postoperative scans. Average forward elevation improved from 50° (preoperative) to 98° (range 35°-150°). The mean improvement in mean Oxford Shoulder Score was 16 (preoperative, 15; postoperative, 31) and the mean improvement in Constant score improvement was 36 (preoperative, 12; postoperative, 48). The mean postoperative American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) score was 64 (range 30-85). CONCLUSION: The use of TT in conjunction with autologous bone graft provides a reliable method of addressing glenoid bone defects in primary and revision shoulder arthroplasty. This graft-trabecular metal composite has been shown to integrate well and remain largely unchanged over a 2-year period. A stable baseplate is essential in difficult primary and revision arthroplasty situations. The stability of this construct in our series is reflected in the satisfactory outcomes.


Assuntos
Artroplastia do Ombro , Articulação do Ombro , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoenxertos , Transplante Ósseo , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Amplitude de Movimento Articular , Estudos Retrospectivos , Articulação do Ombro/diagnóstico por imagem , Articulação do Ombro/cirurgia , Sobrevivência , Resultado do Tratamento
10.
Skeletal Radiol ; 50(2): 267-280, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32789679

RESUMO

Superior capsular reconstruction (SCR) is an emerging surgical technique used to treat patients with irreparable rotator cuff tears. In this procedure, a graft is attached between the superior glenoid and the greater tuberosity, with the aim of optimising glenohumeral joint function and stability. Pre-operative radiological evaluation of patients having such cuff tears is crucial for appropriate patient selection. Such imaging is particularly useful for the assessment of the cuff tear size and location, muscle wasting, fatty infiltration and the presence of any glenohumeral joint arthritis. In addition, post-operative imaging is useful in assessing graft integrity, with specific patterns of graft failure now being recognised on imaging. This article will discuss the indications and contraindications for this procedure, and review the biomechanical concepts of SCR in improving glenohumeral joint stability and restoring the force couples around the joint. The radiological appearances of the intact graft and the various patterns of graft failure will be illustrated, along with various radiological examples.


Assuntos
Lesões do Manguito Rotador , Articulação do Ombro , Humanos , Manguito Rotador , Lesões do Manguito Rotador/diagnóstico por imagem , Lesões do Manguito Rotador/cirurgia , Escápula , Ombro/diagnóstico por imagem , Ombro/cirurgia , Articulação do Ombro/diagnóstico por imagem , Articulação do Ombro/cirurgia
12.
Cancer Res ; 80(8): 1735-1747, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32161100

RESUMO

Checkpoint kinase 1 (CHK1) is a key mediator of the DNA damage response that regulates cell-cycle progression, DNA damage repair, and DNA replication. Small-molecule CHK1 inhibitors sensitize cancer cells to genotoxic agents and have shown single-agent preclinical activity in cancers with high levels of replication stress. However, the underlying genetic determinants of CHK1 inhibitor sensitivity remain unclear. We used the developmental clinical drug SRA737 in an unbiased large-scale siRNA screen to identify novel mediators of CHK1 inhibitor sensitivity and uncover potential combination therapies and biomarkers for patient selection. We identified subunits of the B-family of DNA polymerases (POLA1, POLE, and POLE2) whose silencing sensitized the human A549 non-small cell lung cancer (NSCLC) and SW620 colorectal cancer cell lines to SRA737. B-family polymerases were validated using multiple siRNAs in a panel of NSCLC and colorectal cancer cell lines. Replication stress, DNA damage, and apoptosis were increased in human cancer cells following depletion of the B-family DNA polymerases combined with SRA737 treatment. Moreover, pharmacologic blockade of B-family DNA polymerases using aphidicolin or CD437 combined with CHK1 inhibitors led to synergistic inhibition of cancer cell proliferation. Furthermore, low levels of POLA1, POLE, and POLE2 protein expression in NSCLC and colorectal cancer cells correlated with single-agent CHK1 inhibitor sensitivity and may constitute biomarkers of this phenotype. These findings provide a potential basis for combining CHK1 and B-family polymerase inhibitors in cancer therapy. SIGNIFICANCE: These findings demonstrate how the therapeutic benefit of CHK1 inhibitors may potentially be enhanced and could have implications for patient selection and future development of new combination therapies.


Assuntos
Afidicolina/farmacologia , Quinase 1 do Ponto de Checagem/antagonistas & inibidores , Neoplasias Colorretais/tratamento farmacológico , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Retinoides/farmacologia , Apoptose , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Dano ao DNA , DNA Polimerase I/antagonistas & inibidores , DNA Polimerase I/genética , DNA Polimerase I/metabolismo , DNA Polimerase II/antagonistas & inibidores , DNA Polimerase II/genética , DNA Polimerase II/metabolismo , DNA Polimerase beta , Drogas em Investigação/farmacologia , Inibidores Enzimáticos/farmacologia , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Ligação a Poli-ADP-Ribose/antagonistas & inibidores , Proteínas de Ligação a Poli-ADP-Ribose/genética , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , RNA Interferente Pequeno/análise , RNA Interferente Pequeno/genética
13.
Am J Sports Med ; 47(11): 2686-2690, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31393745

RESUMO

BACKGROUND: Posterior and combined shoulder instabilities have been reported as accounting for only 2% to 5% of cases. More recently, an increased incidence of posterior capsulolabral tear has been reported. PURPOSE: To assess the incidence of posterior and combined labral tears in a large cohort of patients with surgically treated shoulder labral tears. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: This was a retrospective study that evaluated 442 patients who underwent an arthroscopic capsulolabral repair over a 3-year period. Patients were categorized according to the location of their labral tear and whether their injury was sustained during sporting or nonsporting activity. Proportions of labral tears between sporting and nonsporting populations were compared using the chi-square test. RESULTS: Patients had a mean age of 25.9 years and 89.6% were male. Isolated anterior labral tears occurred in 52.9%, with posterior and combined anteroposterior labral tears accounting for 16.3% and 30.8%, respectively. The frequency of posterior and combined lesions was greater in the sporting population compared with the nonsporting population (P = .013). CONCLUSION: Posterior and combined labral tears are more prevalent than previously reported, particularly in the sporting population.


Assuntos
Artroscopia/métodos , Instabilidade Articular/cirurgia , Lesões do Ombro/cirurgia , Articulação do Ombro/cirurgia , Adolescente , Adulto , Idoso , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Esportes , Adulto Jovem
14.
Shoulder Elbow ; 11(3): 182-190, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31210789

RESUMO

BACKGROUND: Outcome scores are useful tools with respect to quantifying how pain and limitations in strength and movement affect the patient's functionality and lifestyle. Three shoulder outcome methods [Oxford, Constant and QuickDASH (Disability of the Arm, Shoulder and Hand)] are commonly used in practice but collectively consist of 34 questions, taking approximately 7 min to complete. We have developed a concise shoulder assessment to derive three equivalent outcome scores in a 12-item patient-reporting questionnaire. METHODS: Outcome scores from 1285 outpatients of an upper limb clinic were collected. The patient cohort consisted of 462 females and 823 males with a mean (SD) age of 47.2 (16.79) years (range 13 years to 90 years). Using a correlation matrix, a 12-item questionnaire was drafted. The combined shoulder assessment was validated by 227 patients; consisting of 101 females and 126 males with a mean (SD) age of 47.91 (16.63) years (range 13 years to 88 years). RESULTS: Agreement was achieved between the two methods, with an equivalent Oxford Shoulder Score intraclass correlation (ICC) of 0.930, equivalent Constant Shoulder Score ICC of 0.942 and equivalent QuickDASH ICC of 0.869. Bland-Altman analyses showed no systematic differences. Large effect sizes highlighted the responsiveness to change. CONCLUSIONS: The new combined shoulder assessment is a more convenient and patient-friendly method to obtain equivalent Oxford, Constant and QuickDASH shoulder outcome scores.

15.
J Med Chem ; 62(5): 2447-2465, 2019 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-30779566

RESUMO

A series of imidazo[1,2- b]pyridazin-8-amine kinase inhibitors were discovered to allosterically inhibit the endoribonuclease function of the dual kinase-endoribonuclease inositol-requiring enzyme 1α (IRE1α), a key component of the unfolded protein response in mammalian cells and a potential drug target in multiple human diseases. Inhibitor optimization gave compounds with high kinome selectivity that prevented endoplasmic reticulum stress-induced IRE1α oligomerization and phosphorylation, and inhibited endoribonuclease activity in human cells. X-ray crystallography showed the inhibitors to bind to a previously unreported and unusually disordered conformation of the IRE1α kinase domain that would be incompatible with back-to-back dimerization of the IRE1α protein and activation of the endoribonuclease function. These findings increase the repertoire of known IRE1α protein conformations and can guide the discovery of highly selective ligands for the IRE1α kinase site that allosterically inhibit the endoribonuclease.


Assuntos
Endorribonucleases/antagonistas & inibidores , Endorribonucleases/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/metabolismo , Regulação Alostérica , Biopolímeros/metabolismo , Cristalografia por Raios X , Dimerização , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Endorribonucleases/química , Células HEK293 , Humanos , Fosforilação , Conformação Proteica , Inibidores de Proteínas Quinases/metabolismo , Proteínas Serina-Treonina Quinases/química
17.
Am J Sports Med ; 46(12): 2969-2974, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30198752

RESUMO

BACKGROUND: Traumatic glenohumeral dislocation of the shoulder is one of the most common shoulder injuries, especially among adolescent athletes. The treatment of instability for young athletes continues to be controversial owing to high recurrence rates. PURPOSE: To investigate the recurrence rate of shoulder instability after arthroscopic capsulolabral repair for adolescent contact and collision athletes. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Sixty-seven patients aged <18 years underwent an arthroscopic labral repair over a 5-year period. The mean ± SD age of the cohort was 16.3 ± 0.9 years (range, 14-17 years) and consisted of 1 female and 66 males. All patients were contact athletes, with 62 of 67 playing rugby. Demographic, clinical, and intraoperative data for all patients with shoulder instability were recorded in our database. Recurrence rates were recorded and relative risks calculated. RESULTS: At a follow-up of 33 ± 20 months, 34 of 67 patients had recurrent instability for an overall recurrence rate of 51% among adolescent contact athletes after arthroscopic labral repair surgery. The mean time to recurrence was 68.1 ± 45.3 weeks. All recurrences occurred as a result of a further sporting injury. Relative risk analysis demonstrated that athletes aged <16 years had 2.2 (95% CI, 1.2-2.1) times the risk of developing a further instability episode as compared with athletes aged ≥16 years at the time of index surgery ( P = .0002). The recurrence rate among adolescent athletes after bony Bankart repairs was 57.9% versus 47.9% for soft tissue labral repairs ( P = .4698). The incidence of Hill-Sachs lesions ( P = .0002) and bony Bankart lesions ( P = .009) among adolescent athletes was significantly higher than among adult controls ( P = .002). The presence of bone loss did not lead to a significant increase in recurrence rate over and above the effect of age. CONCLUSION: Adolescent contact athletes undergoing arthroscopic labral repair have an overall recurrence rate of 51%. Rugby players who undergo primary arthroscopic shoulder stabilization aged <16 years have 2.2 times the risk of developing a further instability episode when compared with athletes aged ≥16 years at the time of index surgery, with a recurrence rate of 93%.


Assuntos
Artroscopia/métodos , Atletas , Lesões de Bankart/cirurgia , Futebol Americano/lesões , Instabilidade Articular/cirurgia , Lesões do Ombro/cirurgia , Adolescente , Lesões de Bankart/complicações , Lesões de Bankart/diagnóstico , Feminino , Seguimentos , Humanos , Instabilidade Articular/etiologia , Instabilidade Articular/fisiopatologia , Masculino , Estudos Prospectivos , Recidiva , Lesões do Ombro/complicações , Lesões do Ombro/diagnóstico , Articulação do Ombro/cirurgia , Fatores de Tempo
18.
Cancer Chemother Pharmacol ; 82(5): 911-912, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30173339

RESUMO

The corresponding author of this article has informed us of concerns about the immunoblots in Fig. 2 which were carried out in the collaborating laboratory of Professor Ann Jackman.

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