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1.
Arch Orthop Trauma Surg ; 144(2): 611-618, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37950763

RESUMO

PURPOSE: The aim of this prospective cohort study was to assess the factual accuracy, completeness of medical information, and potential harmfulness of incorrect conclusions by medical professionals in automatically generated texts of varying complexity (1) using ChatGPT, Furthermore, patients without a medical background were asked to evaluate comprehensibility, information density, and conclusion possibilities (2). METHODS: In the study, five different simplified versions of MRI findings of the knee of different complexity (A: simple, B: moderate, C: complex) were each created using ChatGPT. Subsequently, a group of four medical professionals (two orthopedic surgeons and two radiologists) and a group of 20 consecutive patients evaluated the created reports. For this purpose, all participants received a group of simplified reports (simple, moderate, and severe) at intervals of 1 week each for their respective evaluation using a specific questionnaire. Each questionnaire consisted of the original report, the simplified report, and a series of statements to assess the quality of the simplified reports. Participants were asked to rate their level of agreement with a five-point Likert scale. RESULTS: The evaluation of the medical specialists showed that the findings produced were consistent in quality depending on their complexity. Factual correctness, reproduction of relevant information and comprehensibility for patients were rated on average as "Agree". The question about possible harm resulted in an average of "Disagree". The evaluation of patients also revealed consistent quality of reports, depending on complexity. Simplicity of word choice and sentence structure was rated "Agree" on average, with significant differences between simple and complex findings (p = 0.0039) as well as between moderate and complex findings (p = 0.0222). Participants reported being significantly better at knowing what the text was about (p = 0.001) and drawing the correct conclusions the more simplified the report of findings was (p = 0.013829). The question of whether the text informed them as well as a healthcare professional was answered as "Neutral" across all findings. CONCLUSION: By using ChatGPT, MRI reports can be simplified automatically with consistent quality so that the relevant information is understandable to patients. However, a report generated in this way does not replace a thorough discussion between specialist and patient.


Assuntos
Pessoal de Saúde , Processamento de Linguagem Natural , Humanos , Estudos Prospectivos , Articulação do Joelho , Imageamento por Ressonância Magnética
2.
Arch Orthop Trauma Surg ; 143(8): 5143-5148, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36547750

RESUMO

BACKGROUND: Hip abductor tear (HAT) is an increasingly diagnosed cause of refractory lateral hip pain and dysfunction, affecting 10-25% of the general population. PURPOSE: (1) to determine the rate of return to activity and to assess the physical and recreational activity of patients undergoing open hip abductor repair (oHATr) and (2) to describe the modification or initiation of new sports disciplines. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A total of 28 patients (29 hips) who underwent an oHATr were prospectively analyzed at a midterm follow-up of 3.5 (range 2-5) years. The sports and recreational activity levels, as well as type of sports practiced before and after surgery, and The Veterans RAND 12 Item Health Survey (VR-12) were assessed via questionnaire. RESULTS: At the final follow-up, all patients were active in sports after surgery. The duration and frequency of sports activities showed a slight decrease (48-42 min per week and 3.2-2.9 sessions per week, respectively) (p = 0.412 and 0.135, respectively). The VR-12 had a score of 45 (13.12-63.18) points for the physical component and 41 (32-53.8) points for the mental component. 100% of the patients would undergo the surgery again. 95% of patients were satisfied with the overall results of the surgical outcome, with 98% satisfied with their hip pain relief and ability to undertake daily and work activities. Moreover, 94% were satisfied with their ability to return to recreational activities. The failure rate in our cohort was approximately 14%. CONCLUSION: All patients who underwent an oHATr were able to return at least to one type of sport. This cohort was highly satisfied with their sports involvement and recreational activity achievement. In addition, 88% of patients reported that oHATr improved sports activity. There was a shift from higher to lower impact sports. Furthermore, just 3 hips present a retear after surgery.


Assuntos
Quadril , Volta ao Esporte , Humanos , Resultado do Tratamento , Seguimentos , Articulação do Quadril/cirurgia , Dor , Estudos Retrospectivos , Artroscopia/métodos
3.
Arch Orthop Trauma Surg ; 143(10): 6431-6437, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36995474

RESUMO

PURPOSE: The aim of this study was the evaluation of pain, function, and overall satisfaction after total hip arthroplasty (THA) using three different standard surgical approaches (DAA (direct anterior approach), lateral, and posterior approach) 2 years postoperatively. Additionally, we compared the results with recently published results of the same study population 6 weeks postoperatively. METHODS: In a multisurgeon, prospective, single-center cohort study, a total of initial 188 patients who underwent total hip arthroplasty (THA) between February 2019 and April 2019 were analyzed on pain, function, and satisfaction within the first days, 6 weeks, and 2 years postoperatively according to three different approaches (DAA, lateral, and posterior approach). Our research group recently published results directly and 6 weeks postoperatively. We evaluated the same study collectively 2 years postoperatively and compared the results with the data 6 weeks postoperatively. One hundred twenty-five patients could be included. Outcome parameters for the present study were the pain level according to the visual analogue scale (VAS), the modified Harris hip score (mHHS), and an overall satisfaction scale 2 years postoperatively. RESULTS: Mean overall satisfaction 2 years postoperatively was 9.7 ± 1 (3-10). Satisfaction was significantly better for the DAA than for the lateral approach (p = 0.005). There were no significant differences between the lateral and posterior approaches (p = 0.06) and between the DAA and the posterior approaches (p = 0.11). In total, the mean pain level was 0.4 ± 0.9 (0-5) at 6 weeks and 0.5 ± 1.1 (0-7) at 2 years postoperatively (p = 0.3). Regarding the different approach groups, pain levels 6 weeks and 2 years postoperatively were significantly lower for the DAA than for the lateral approach (p = 0.02). There were no significant differences between DAA and posterior approach (p = 0.05) and the lateral and posterior approach (p = 0.26). The mean mHHS significantly increased from 84.7 + 14.5 (37.4-100) 6 weeks to 95 + 12.5 (23.1-100.1) 2 years postoperatively (p < 0.0001). Regarding the different approaches, mHHS was significantly higher for the DAA than for the lateral approach (p = 0.03). Differences between the DAA and the posterior approach (p = 0.11) and between the lateral and posterior approaches (p = 0.24) were insignificant. CONCLUSION: At 2 years postoperative, DAA showed significantly better overall satisfaction, pain level, and mHHS than the lateral approach. The differences between DAA and the posterior approach and lateral and posterior approaches were insignificant. Whether the superior results of the DAA to the lateral approach persist over a longer period must be clarified by further studies. STUDY DESIGN: Prospective cohort study, level of evidence 2.


Assuntos
Artroplastia de Quadril , Humanos , Artroplastia de Quadril/métodos , Estudos de Coortes , Duração da Cirurgia , Estudos Prospectivos , Resultado do Tratamento
4.
Arch Orthop Trauma Surg ; 143(8): 4763-4772, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36705760

RESUMO

BACKGROUND: Glenoid defects can be addressed traditionally by asymmetric reaming or by bone-preserving correction to a more lateral joint line by bone or metal augmented baseplates in reverse shoulder arthroplasties. While there is more evidence in literature regarding the outcome and complications of Bony Increased Offset Reversed Shoulder Arthroplasty (BIO-RSA), there is minimal reported experience with the outcome after metal glenoid augments. The aim of this study was to determine whether a metal augment can correct the glenoid deformity in an anatomic manner. METHODS: Glenoid morphology and deformity were determined in 50 patients with Walch type B1, B2, D and Favard type E0-E3 glenoid defects using preoperative radiographic and computed tomography (CT) analysis. All patients received a preoperative planning CT with 3D planning, and measurements of glenoid inclination (in 3 planes proximal, middle, distal), reversed shoulder arthroplasty angle (RSA) and glenoid version were obtained. All patients had a pathologic inclination in the coronal or frontal planes of > 10°. Above the threshold of 10° pathological glenoid version or inclination metal hemi-augments of 10°, 20°, or 30° were used which allow an individual 360° augment positioning according to the patient glenoid deformity. RESULTS: The mean preoperative numbers of the glenoid version demonstrate that most glenoids were in retroversion and superior inclination. In total 2410° wedges, 1820° wedges and 8 30° wedges were used. In the majority of cases, the wedge was positioned posteriorly and/or cranially between 10:00 and 12:00 o'clock, which allows a correction in a 3D manner of the glenoid inclination and version. The mean RSA angle could be corrected from 22.76 ± 6.06 to 0.19° ± 2.7 (p < 0.0001). The highest retroversion of the glenoid is evidenced in the proximal section and it could be corrected from - 23.32° ± 4.56 to - 6.74° ± 7.75 (p < 0.0001) and in the middle section from - 18.93° ± 3.35 to - 7.66° ± 5.28 (p < 0.0001). A mean sphere bone overhang distance (SBOD) of 5.70 ± 2.04 mm was found in order to avoid or minimize relevant scapular notching. CONCLUSION: By using a new 360° metal-augmented baseplate, the preoperative pathological inclination and retroversion can be corrected without medialization of the joint line. Future clinical results will show whether this bone-preserving procedure improves also the clinical outcomes as compared to asymmetric medialized reaming or wedged BIO-RSA. LEVEL OF EVIDENCE: Level IV, Case series.


Assuntos
Artroplastia do Ombro , Cavidade Glenoide , Articulação do Ombro , Humanos , Articulação do Ombro/diagnóstico por imagem , Articulação do Ombro/cirurgia , Cavidade Glenoide/diagnóstico por imagem , Cavidade Glenoide/cirurgia , Artroplastia do Ombro/métodos , Escápula/cirurgia , Tomografia Computadorizada por Raios X/métodos , Estudos Retrospectivos
5.
Platelets ; 33(1): 98-109, 2022 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-33393414

RESUMO

Recent years have witnessed the introduction of ex vivo expanded dermal fibroblasts for several cell therapy and tissue-engineering applications, including the treatment of facial scars and burns, representing a promising cell type for regenerative medicine. We tested different in-house produced human platelet lysate (HPL) solutions against fetal bovine serum as supplements for in vitro fibroblast expansion by comparing cell yield, molecular marker expression, extracellular matrix (ECM) generation, genomic stability and global gene expression. Our in-house produced HPL supported fibroblast growth at levels similar to those for FBS and commercial HPL products and was superior to AB human serum. Cells grown in HPL maintained a fibroblast phenotype (VIM+, CD44+, CD13+, CD90+), ECM generation capacity (FN+, COL1+) and a normal karyotype, although gene expression profiling revealed changes related to cell metabolism, adhesion and cellular senescence. The HPL manufacturing process was validated within a GMP compliant system and the solution was stable at -80ºC and -20ºC for 2 years. Dermal fibroblasts expanded in vitro with HPL maintain a normal karyotype and expression of fibroblast markers, with only minor changes in their global gene expression profile. Our in-house produced GMP-HPL is an efficient, safe and economical cell culture supplement that can help increase the healthcare activity of blood transfusion centers through the re-use of transfusional plasma and platelets approaching their expiration date. Currently, our HPL solution is approved by the Spanish Agency of Medicines and Medical Devices and is being used in the manufacture of cell therapy products.Abbreviations: AB plasma: plasma group AB; ABHS: AB Human Serum; ABHS+GF: AB Human Serum supplemented with growth factors; ANOVA: Analysis of variance; ATMPs: Advanced Therapies for Medicinal Products; CPE: cytopathic effect; DEGs: Differentially expressed genes; DMEM: Dulbecco's modified Eagle's Medium; ECM: Extracellular matrix; ELISA: enzyme-linked immunosorbent assay; FBS: Fetal bovine serum; FDR: False discovery rate; FGF: Fibroblast growth factor; GMP: Good manufacturing practice; HPL: Human platelet lysate; HPL-CM: commercial human platelet lysate; MSCs: mesenchymal stem cells; NEAA: non-essential amino acids; P/S: penicillin/streptomycin; PBS: phosphate buffered saline; PC: leukodepleted platelet concentrate; PCR: polymerase chain reaction; PDGF: Platelet-derived growth factor; PDGFRA: Platelet-derived growth factor receptor alpha; qPCR: quantitative polymerase chain reaction; RNA: Ribonucleic acid; RT: Room temperature; TAC: Transcriptome analysis console; TGF-ß: Transforming growth factor beta.


Assuntos
Plaquetas/metabolismo , Fibroblastos/metabolismo , Animais , Bovinos , Feto , Humanos
6.
BMC Musculoskelet Disord ; 23(1): 696, 2022 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-35869488

RESUMO

BACKGROUND: Chronic hip pain due to osteoarthritis or hip dysplasia has been shown to negatively affect many daily life aspects. One aspect, however, which persists underestimated is sexual health. The number of total hip arthroplasties (THA) are increasing, especially in young patients who have high functional expectations, not only to pain relief, but to an increase in hip mobility and quality of life as well as sexual activity. AIM: (1) to report the demographic factors, (2) the sexual activity before and after THA, as well as the concerns related to sexual activity after THA and (3) the patient-reported outcome measurements (PROMs) in sexually active male patients. METHODS: We evaluated the results of patients between 18 and 65 years of age following primary cementless short femoral stem THA using a direct anterior approach (DAA) at a midterm follow-up of 4 years. A web-based questionnaire (via SurveyMonkey) was chosen to assess frequency, positions, complaints, fears, dealing with the questions and PROMs. Our patients sexual activity was via The Sexual Health Inventory for Men (SHIM) validated. RESULTS: Patients resumed their sexual activities after 6 weeks. The two main causes of difficulty in sexual activity before surgery were pain and limitation of the range of motion of the hip joint. Patients experienced less pain and an improvement in hip range of motion after THA. 89% of patients expressed a desire for more detailed and specific information on the subject. The patients foremost concern about muscle weakness, surgical scar or fear of dislocation. After 4 years follow-up our patients presented a significant improvement of the modified Harris Hip Score (mHHS) from 34.1 preoperative to 92.6 after THA. CONCLUSION: THA improves the quality in sexual life, in relation to less pain and improvement in the range of motion, but not in the frequency of sexual activity. Men's sexual positions required less mobility and could therefore be considered safer.


Assuntos
Artroplastia de Quadril , Prótese de Quadril , Artroplastia de Quadril/métodos , Articulação do Quadril/cirurgia , Humanos , Masculino , Dor , Qualidade de Vida , Estudos Retrospectivos , Comportamento Sexual , Resultado do Tratamento
7.
BMC Musculoskelet Disord ; 23(1): 251, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35291994

RESUMO

BACKGROUND: Pelvic fractures are often associated with spine injury in polytrauma patients. This study aimed to determine whether concomitant spine injury influence the surgical outcome of pelvic fracture. METHODS: We performed a retrospective analysis of data of patients registered in the German Pelvic Registry between January 2003 and December 2017. Clinical characteristics, surgical parameters, and outcomes were compared between patients with isolated pelvic fracture (group A) and patients with pelvic fracture plus spine injury (group B). We also compared apart patients with isolated acetabular fracture (group C) versus patients with acetabular fracture plus spine injury (group D). RESULTS: Surgery for pelvic fracture was significantly more common in group B than in group A (38.3% vs. 36.6%; p = 0.0002), as also emergency pelvic stabilizations (9.5% vs. 6.7%; p < 0.0001). The mean time to emergency stabilization was longer in group B (137 ± 106 min vs. 113 ± 97 min; p < 0.0001), as well as the mean time until definitive stabilization of the pelvic fracture (7.3 ± 4 days vs. 5.4 ± 8.0 days; p = 0.147). The mean duration of treatment and the morbidity and mortality rates were all significantly higher in group B (p < 0.0001). Operation time was significantly shorter in group C than in group D (176 ± 81 min vs. 203 ± 119 min, p < 0.0001). Intraoperative blood loss was not significantly different between the two groups with acetabular injuries. Although preoperative acetabular fracture dislocation was slightly less common in group D, postoperative fracture dislocation was slightly more common. The distribution of Matta grades was significantly different between the two groups. Patients with isolated acetabular injuries were significantly less likely to have neurological deficit at discharge (94.5%; p < 0.0001). In-hospital complications were more common in patients with combined spine plus pelvic injuries (groups B and D) than in patients with isolated pelvic and acetabular injury (groups A and C). CONCLUSIONS: Delaying definitive surgical treatment of pelvic fractures due to spinal cord injury appears to have a negative impact on the outcome of pelvic fractures, especially on the quality of reduction of acetabular fractures.


Assuntos
Fraturas do Quadril , Ossos Pélvicos , Fraturas da Coluna Vertebral , Humanos , Ossos Pélvicos/lesões , Ossos Pélvicos/cirurgia , Sistema de Registros , Estudos Retrospectivos , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/cirurgia
8.
Arch Orthop Trauma Surg ; 142(11): 3059-3065, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33938986

RESUMO

INTRODUCTION: This retrospective study aimed to compare activity levels before and at mid-term follow-up after primary cementless total hip arthroplasty (THA) in patients older than 75 years. MATERIALS AND METHODS: A cohort of 79 patients with a mean age at surgery of 78 years (range 76-84 years) was evaluated 6.3 years (range 4-8 years) after cementless THA due to osteoarthritis and was followed up with a questionnaire to determine their activity level. Pre- and post-operative recreational activities were assessed at routine follow-up using the University of California, Los Angeles activity score, and the Schulthess Clinic sports and activity questionnaire. Post-operative health-related quality of life was measured using Veterans Rand 12-item survey (VR-12). RESULTS: Six years after THA, 72% of preoperatively active patients had returned to activity. Comparing activity preoperatively (before the onset of symptoms) and 6 years after THA, the number of disciplines and session length has decreased significantly. A significant decline in high-impact activities was observed, while participation in low-impact activities significantly increased. CONCLUSION: The majority of patients maintained a recreational activity level in the mid-term after primary cementless THA. However, a change in disciplines toward low-impact activities was observed.


Assuntos
Artroplastia de Quadril , Prótese de Quadril , Osteoartrite , Esportes , Idoso , Idoso de 80 Anos ou mais , Seguimentos , Humanos , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento
9.
Development ; 145(7)2018 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-29540498

RESUMO

Photoreceptors in the crystalline Drosophila eye are recruited by receptor tyrosine kinase (RTK)/Ras signaling mediated by Epidermal growth factor receptor (EGFR) and the Sevenless (Sev) receptor. Analyses of an allelic deletion series of the mir-279/996 locus, along with a panel of modified genomic rescue transgenes, show that Drosophila eye patterning depends on both miRNAs. Transcriptional reporter and activity sensor transgenes reveal expression and function of miR-279/996 in non-neural cells of the developing eye. Moreover, mir-279/996 mutants exhibit substantial numbers of ectopic photoreceptors, particularly of R7, and cone cell loss. These miRNAs restrict RTK signaling in the eye, since mir-279/996 nulls are dominantly suppressed by positive components of the EGFR pathway and enhanced by heterozygosity for an EGFR repressor. miR-279/996 limit photoreceptor recruitment by targeting multiple positive RTK/Ras signaling components that promote photoreceptor/R7 specification. Strikingly, deletion of mir-279/996 sufficiently derepresses RTK/Ras signaling so as to rescue a population of R7 cells in R7-specific RTK null mutants boss and sev, which otherwise completely lack this cell fate. Altogether, we reveal a rare setting of developmental cell specification that involves substantial miRNA control.


Assuntos
Drosophila/metabolismo , Olho/metabolismo , MicroRNAs/metabolismo , Células Fotorreceptoras de Invertebrados/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Animais , Diferenciação Celular/genética , Drosophila/embriologia , Proteínas de Drosophila/metabolismo , Olho/embriologia , Proteínas do Olho/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Imuno-Histoquímica , Organogênese/genética , Transdução de Sinais
10.
Crit Rev Biotechnol ; 40(3): 283-291, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32054356

RESUMO

Recent advances in stem cell biology and molecular engineering have improved and simplified the methodology employed to create experimental chimeras, highlighting their value in basic research and broadening the spectrum of potential applications. Experimental chimeras have been used for decades during the generation of murine genetic models, this being especially relevant in developmental and regeneration studies. Indeed, their value for the research and modeling of human diseases was recognized by the 2007 Nobel Prize to Mario Capecchi, Martin Evans, and Oliver Smithies. More recently, their potential application in regenerative medicine has generated a lot of interest, particularly the enticing possibility to generate human organs for transplantation in livestock animals. In this review, we provide an update on interspecific chimeric organogenesis, its possibilities, current limitations, alternatives, and ethical issues.


Assuntos
Quimera/metabolismo , Animais , Temas Bioéticos , Quimera/classificação , Células-Tronco Embrionárias , Humanos , Camundongos , Modelos Genéticos , Organogênese , Medicina Regenerativa , Quimeras de Transplante
11.
PLoS Genet ; 11(6): e1005245, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26042831

RESUMO

While most miRNA knockouts exhibit only subtle defects, a handful of miRNAs are profoundly required for development or physiology. A particularly compelling locus is Drosophila mir-279, which was reported as essential to restrict the emergence of CO2-sensing neurons, to maintain circadian rhythm, and to regulate ovarian border cells. The mir-996 locus is located near mir-279 and bears a similar seed, but they otherwise have distinct, conserved, non-seed sequences, suggesting their evolutionary maintenance for separate functions. We generated single and double deletion mutants of the mir-279 and mir-996 hairpins, and cursory analysis suggested that miR-996 was dispensable. However, discrepancies in the strength of individual mir-279 deletion alleles led us to uncover that all extant mir-279 mutants are deficient for mature miR-996, even though they retain its genomic locus. We therefore engineered a panel of genomic rescue transgenes into the double deletion background, allowing a pure assessment of miR-279 and miR-996 requirements. Surprisingly, detailed analyses of viability, olfactory neuron specification, and circadian rhythm indicate that miR-279 is completely dispensable. Instead, an endogenous supply of either mir-279 or mir-996 suffices for normal development and behavior. Sensor tests of nine key miR-279/996 targets showed their similar regulatory capacities, although transgenic gain-of-function experiments indicate partially distinct activities of these miRNAs that may underlie that co-maintenance in genomes. Altogether, we elucidate the unexpected genetics of this critical miRNA operon, and provide a foundation for their further study. More importantly, these studies demonstrate that multiple, vital, loss-of-function phenotypes can be rescued by endogenous expression of divergent seed family members, highlighting the importance of this miRNA region for in vivo function.


Assuntos
MicroRNAs/genética , Animais , Ritmo Circadiano/genética , Drosophila/genética , Drosophila/metabolismo , Genoma de Inseto , MicroRNAs/metabolismo , Mutação , Neurogênese/genética , Fenótipo
12.
Development ; 138(1): 107-16, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21115609

RESUMO

Although most metazoan genes undergo alternative splicing, the functional relevance of the majority of alternative splicing products is still unknown. Here we explore this problem in the Drosophila Hox gene Ultrabithorax (Ubx). Ubx produces a family of six protein isoforms through alternative splicing. To investigate the functional specificity of the Ubx isoforms, we studied their role during the formation of the Drosophila halteres, small dorsal appendages that are essential for normal flight. Our work shows that isoform Ia, which is encoded by all Ubx exons, is more efficient than isoform IVa, which lacks the amino acids coded by two small exons, in controlling haltere development and regulating Ubx downstream targets. However, our experiments also demonstrate that the functional differences among the Ubx isoforms can be compensated for by increasing the expression levels of the less efficient form. The analysis of the DNA-binding profiles of Ubx isoforms to a natural Ubx target, spalt, shows no major differences in isoform DNA-binding activities, suggesting that alternative splicing might primarily affect the regulatory capacity of the isoforms rather than their DNA-binding patterns. Our results suggest that to obtain distinct functional outputs during normal development genes must integrate the generation of qualitative differences by alternative splicing to quantitative processes affecting isoform protein expression levels.


Assuntos
Proteínas de Drosophila/metabolismo , Proteínas de Homeodomínio/metabolismo , RNA/metabolismo , Fatores de Transcrição/metabolismo , Processamento Alternativo/genética , Processamento Alternativo/fisiologia , Animais , Western Blotting , Drosophila , Proteínas de Drosophila/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Proteínas de Homeodomínio/genética , Fenótipo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , RNA/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Transcrição/genética
13.
BMJ Case Rep ; 15(5)2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35537775

RESUMO

We report a case of a fractured titanium alloy (Ti6Al4V) femoral stem 2 years after revision (debridement, antibiotics and implant retention due to periprosthetic joint infection) total hip arthroplasty (THA). Material analysis revealed a superficial abnormality on the upper neck surface caused by local melting with electrocautery probably acting as a stress amplifier. This lesion presumably was the trigger of a fatigue fracture with typical features on the fracture surface. Electrocautery should therefore be avoided in case of revision THA or used with utmost care to avoid contact with the femoral stem.


Assuntos
Artroplastia de Quadril , Fraturas Ósseas , Prótese de Quadril , Artroplastia de Quadril/efeitos adversos , Colo do Fêmur , Fraturas Ósseas/cirurgia , Prótese de Quadril/efeitos adversos , Humanos , Desenho de Prótese , Falha de Prótese , Reoperação , Titânio
14.
Stem Cells Transl Med ; 11(8): 805-813, 2022 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-35830540

RESUMO

The development of cell-, gene- and tissue engineering (CGT)-based therapies must adhere to strict pharmaceutical quality management standards, as for any other biological or small-molecule drug. However, early developments often failed to fully comply with good laboratory practices (GLP) in non-clinical safety studies. Despite an upward trend of positive opinions in marketing authorization applications, evidence of adherence to the principles of GLP is not openly reported; therefore, their relative impact on the overall quality of the product development program is unknown. Herein we investigated the actual degree of GLP implementation and the underlying factors impeding full compliance in non-clinical developments of CGT-based marketed medicines in the EU and USA, including (i) the co-existence of diverse quality management systems of more strategic value for small organizations, particularly current Good Manufacturing Practices n(GMP); (ii) lack of regulatory pressure to pursue GLP certification; and (iii) the involvement of public institutions lacking a pharmaceutical mindset and resources. As a final reflection, we propose conformity to good research practice criteria not as a doctrinaire impediment to scientific work, but as a facilitator of efficient clinical translation of more effective and safer innovative therapies.


Assuntos
Terapias em Estudo , Preparações Farmacêuticas
15.
J Clin Med ; 10(21)2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34768684

RESUMO

PURPOSE: To (1) describe the prevalence of abnormal sleep quality in patients with hip abductor tears (HAT), to (2) determine whether sleep quality improves after open HAT repair, and to (3) to report clinical short-term outcomes in patients undergoing open HAT repair. METHODS: The data of 28 patients (29 hips) who underwant open HAT repair were prospectively analyzed at midterm follow-up. The Pittsburgh Sleep Quality Index (PSQI), modified Harris Hip Score (mHHS), the University of California, Los Angeles activity scale (UCLA), and Visual Analog Scale (VAS) for pain were determined via questionnaire. Paired t-tests were applied to compare preoperative and post-operative Patient-reported Outcome Measures (PROMs). Logistic regression was performed to determine the association between PSQI improvement achievement and demographic variables (laterality, sex, age, body-mass-index (BMI), and preoperative mHHS). The minimal clinically important difference (MCID) was calculated for the mHHS. RESULTS: A total of 28 patients were included. Four patients (14.3%) suffered post-operative complications after open HAT repair. The predominance of patients was female (77.4%), with a mean age of 60 ± 13 years. The average follow-up was 30.35 ± 16.62 months. Preoperatively, 27 (96.4%) patients experienced poor sleep quality (PSQI > 5); at follow-up, 7 (25%) patients experienced poor sleep quality. Univariate logistical regression analysis demonstrated no significant association between preoperative demographic data and achieving postoperative PSQI < 5. The MCID of mHHS was calculated to be 12.5. Overall, 90% of patients achieved MCID for mHHS. CONCLUSION: Preoperative sleep quality was impaired in 96.4% of HAT patients (PSQI > 5). However, these patients showed an improvement in sleep disturbances after open HAT repair in the early postoperative period. Ninety percent of patients showed significant improvements in mHHS and achieved the corresponding MCID. LEVEL OF EVIDENCE: Case series; Level IV.

16.
J Clin Med ; 10(20)2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34682767

RESUMO

BACKGROUND: The management of degenerative hip diseases in young patients remains a challenge. Despite the improvement of hip-preserving procedures, total hip arthroplasty (THA) may be required in some instances. In addition, young patients undergoing THA have high expectations concerning their postoperative level of activity. PURPOSE: (1) to define the sports activity level and the return to sports after THA, (2) to describe the modification or initiation of new sports disciplines, and (3) to report the clinically meaningful outcomes after THA in patients younger than 40 years. METHODS: A total of 36 patients (40 hips) were prospectively analyzed at a midterm follow-up of 3.9 years. The modified Harris Hip Score (mHHS); the Visual Analog Scale (VAS) for pain; the University of California, Los Angeles (UCLA) activity scale; and sports and recreational activity levels were assessed via questionnaire. The minimal clinically important difference (MCID) was determined by calculating half of the standard deviation, and the substantial clinical benefit (SCB) as well as patient acceptable symptomatic state (PASS), were calculated by the anchor method for the mHHS. RESULTS: At the final follow-up, there was a significant improvement in mHHS (34.1 to 92.6; p < 0.0001), UCLA (3.2 to 7.6; p < 0.0001), and VAS for pain (8 to 1; p < 0.0001). More patients were active in sports at follow-up than before surgery (44% to 92%, p < 0.0001). In addition, the duration and frequency of sports activities showed a significant increase (p < 0.0001). The MCID, SCB and PASS for mHHS were 89% and 58%, respectively. No revision surgery had to be performed. CONCLUSION: This study showed that a large proportion of patients under 40 years of age who underwent THA increased their physical activity. Eighty-six percent of the patients were highly active, with a UCLA score ≥ 7. Furthermore, the reported MCID, SCB, and PASS for mHHS were achieved by more than 80% of patients.

17.
Knee ; 28: 64-71, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33310667

RESUMO

BACKGROUND: Unicompartmental osteoarthrosis increasingly affects younger patients who have high expectations concerning their postoperative level of activity. However, there is no available data on the activity level after fixed-bearing lateral unicompartmentalkneearthroplasty (UKA). The aim of this study was to report sports activity after fixed-bearing lateral UKA with a minimum two-year follow up. METHODS: Nineteen patients were surveyed to determine their sporting activities at a mean follow up of 4.6 years (range 2.0-9.7 years) after fixed-bearing lateral UKA. We also assessed the Knee Injury and Osteoarthritis Outcome Score Joint Replacement (KOOS JR) Score and the University of California, Los Angeles activity scale (UCLA scale) at baseline and latest follow up. RESULTS: Before the onset of the first symptoms, 15 of 19 patients were active in at least one sport compared with 13 of 19 patients after surgery. Eighty-six per cent of the patients returned to activity. Within 6 months, 68% returned to their activities after surgery. The mean postoperative UCLA score was 6.4 (±1.3). Half of the patients reached a high activity level (UCLA ≥ 7). Most common activities after surgery were long walks, biking and hiking. High-impact activities showed a significant decrease. CONCLUSION: Eighty-six per cent of the patients were able to return to regular recreational and sporting activities. In general, a shift from high-impact to low-impact activities was observed. There was no difference in the number of disciplines performed. Overall, the session length and frequency remained unchanged. However, male patients and younger patients participated in sports less frequently compared with preoperative levels.


Assuntos
Artroplastia do Joelho/métodos , Osteoartrite do Joelho/cirurgia , Volta ao Esporte , Adulto , Idoso , Exercício Físico , Feminino , Seguimentos , Humanos , Articulação do Joelho/cirurgia , Prótese do Joelho , Masculino , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Desenho de Prótese , Esportes , Inquéritos e Questionários , Resultado do Tratamento
18.
J Clin Med ; 10(5)2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33801479

RESUMO

PURPOSE: It remains controversial whether cementless femoral components are safe in elderly patients. The aim of this study was (1) to determine the stem survival rate in patients >75 years of age who were treated with an uncemented femoral component and (2) to report clinically significant results on a mid-term follow-up. METHODS: 107 total hip arthroplasties (THA) were retrospectively evaluated in 97 patients over 75 years of age (mean age 78 years, range 75-87) treated with an uncemented femoral stem. The minimum follow-up was five years (mean 6.4 years, range 5-8). Stem survival rates, clinically meaningful outcomes, and incidence of complications were evaluated. RESULTS: Kaplan-Meier survival analysis, with the endpoint revision for any reason, showed a 6.4-year survival rate of 98% (95% CI, 95-99%; 63 hips at risk). The survival rates were comparable for male and female patients (log-rank test, p = 0.58). The modified Harris Hip Score (mHHS) improved from 42.2 (12 to 85) points to 81.1 (22 to 97) points (p < 0.0001). Mid-term minimal clinically important difference (MCID), substantial clinical benefit (SCB), and patient acceptable symptomatic state (PASS) were 25, 84, and 70, respectively. CONCLUSION: An uncemented stem is a viable option in patients over 75 years with good clinical outcomes and survivorship. Periprosthetic fractures were not a relevant failure mechanism with the stem used.

19.
Eur J Trauma Emerg Surg ; 47(3): 683-692, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33742223

RESUMO

PURPOSE: To analyse acute cholecystitis (AC) management during the first pandemic outbreak after the recommendations given by the surgical societies estimating: morbidity, length of hospital stay, mortality and hospital-acquired SARS-CoV-2 infection rate. METHODS: Multicentre-combined (retrospective-prospective) cohort study with AC patients in the Community of Madrid between 1st March and 30th May 2020. 257 AC patients were involved in 16 public hospital. Multivariant binomial logistic regression (MBLR) was applied to mortality. RESULTS: Of COVID-19 patients, 30 were diagnosed at admission and 12 patients were diagnosed during de admission or 30 days after discharge. In non-COVID-19 patients, antibiotic therapy was received in 61.3% of grade I AC and 40.6% of grade II AC. 52.4% of grade III AC were treated with percutaneous drainage (PD). Median hospital stay was 5 [3-8] days, which was higher in the non-surgical treatment group with 7.51 days (p < 0.001) and a 3.25% of mortality rate (p < 0.21). 93.3% of patients with SARS-CoV-2 infection at admission were treated with non-surgical treatment (p = 0.03), median hospital stay was 11.0 [7.5-27.5] days (p < 0.001) with a 7.5% of mortality rate (p > 0.05). In patients with hospital-acquired SARS-CoV-2 infection, 91.7% of grade I-II AC were treated with non-surgical treatment (p = 0.037), with a median hospital stay of 16 [4-21] days and a 18.2% mortality rate (p > 0.05). Hospital-acquired infection risk when hospital stay is > 7 days is OR 4.7, CI 95% (1.3-16.6), p = 0.009. COVID-19 mortality rate was 11.9%, AC severity adjusted OR 5.64 (CI 95% 1.417-22.64). In MBLR analysis, age (OR 1.15, CI 95% 1.02-1.31), SARS-CoV-2 infection (OR 14.49, CI 95% 1.33-157.81), conservative treatment failure (OR 8.2, CI 95% 1.34-50.49) and AC severity were associated with an increased odd of mortality. CONCLUSION: In our population, during COVID-19 pandemic, there was an increase of non-surgical treatment which was accompanied by an increase of conservative treatment failure, morbidity and hospital stay length which may have led to an increased risk hospital-acquired SARS-CoV-2 infection. Age, SARS-CoV-2 infection, AC severity and conservative treatment failure were mortality risk factors.


Assuntos
Antibacterianos/uso terapêutico , COVID-19 , Colecistectomia/estatística & dados numéricos , Colecistite Aguda , Tratamento Conservador , Infecção Hospitalar , Controle de Infecções , COVID-19/diagnóstico , COVID-19/mortalidade , COVID-19/prevenção & controle , Colecistite Aguda/diagnóstico , Colecistite Aguda/epidemiologia , Colecistite Aguda/terapia , Estudos de Coortes , Comorbidade , Tratamento Conservador/métodos , Tratamento Conservador/estatística & dados numéricos , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/virologia , Drenagem/métodos , Drenagem/estatística & dados numéricos , Feminino , Humanos , Controle de Infecções/métodos , Controle de Infecções/organização & administração , Controle de Infecções/normas , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Medição de Risco , SARS-CoV-2 , Espanha/epidemiologia
20.
Stem Cells Transl Med ; 9(9): 1085-1101, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32475061

RESUMO

Intraventricular hemorrhage is a common cause of morbidity and mortality in premature infants. The rupture of the germinal zone into the ventricles entails loss of neural stem cells and disturbs the normal cytoarchitecture of the region, compromising late neurogliogenesis. Here we demonstrate that neural stem cells can be easily and robustly isolated from the hemorrhagic cerebrospinal fluid obtained during therapeutic neuroendoscopic lavage in preterm infants with severe intraventricular hemorrhage. Our analyses demonstrate that these neural stem cells, although similar to human fetal cell lines, display distinctive hallmarks related to their regional and developmental origin in the germinal zone of the ventral forebrain, the ganglionic eminences that give rise to interneurons and oligodendrocytes. These cells can be expanded, cryopreserved, and differentiated in vitro and in vivo in the brain of nude mice and show no sign of tumoral transformation 6 months after transplantation. This novel class of neural stem cells poses no ethical concerns, as the fluid is usually discarded, and could be useful for the development of an autologous therapy for preterm infants, aiming to restore late neurogliogenesis and attenuate neurocognitive deficits. Furthermore, these cells represent a valuable tool for the study of the final stages of human brain development and germinal zone biology.


Assuntos
Hemorragia Cerebral/líquido cefalorraquidiano , Recém-Nascido Prematuro/líquido cefalorraquidiano , Células-Tronco Neurais/patologia , Antígeno AC133/metabolismo , Animais , Hemorragia Cerebral/genética , Endoscopia , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Masculino , Camundongos Nus , Células-Tronco Neurais/transplante
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