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1.
Nat Commun ; 15(1): 5789, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38987539

RESUMEN

The outcome of CRISPR-Cas-mediated genome modifications is dependent on DNA double-strand break (DSB) processing and repair pathway choice. Homology-directed repair (HDR) of protein-blocked DSBs requires DNA end resection that is initiated by the endonuclease activity of the MRE11 complex. Using reconstituted reactions, we show that Cas9 breaks are unexpectedly not directly resectable by the MRE11 complex. In contrast, breaks catalyzed by Cas12a are readily processed. Cas9, unlike Cas12a, bridges the broken ends, preventing DSB detection and processing by MRE11. We demonstrate that Cas9 must be dislocated after DNA cleavage to allow DNA end resection and repair. Using single molecule and bulk biochemical assays, we next find that the HLTF translocase directly removes Cas9 from broken ends, which allows DSB processing by DNA end resection or non-homologous end-joining machineries. Mechanistically, the activity of HLTF requires its HIRAN domain and the release of the 3'-end generated by the cleavage of the non-target DNA strand by the Cas9 RuvC domain. Consequently, HLTF removes the H840A but not the D10A Cas9 nickase. The removal of Cas9 H840A by HLTF explains the different cellular impact of the two Cas9 nickase variants in human cells, with potential implications for gene editing.


Asunto(s)
Proteína 9 Asociada a CRISPR , Sistemas CRISPR-Cas , Roturas del ADN de Doble Cadena , ADN , Humanos , Proteína 9 Asociada a CRISPR/metabolismo , Proteína 9 Asociada a CRISPR/genética , ADN/metabolismo , ADN/genética , Proteína Homóloga de MRE11/metabolismo , Proteína Homóloga de MRE11/genética , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Proteínas Asociadas a CRISPR/metabolismo , Proteínas Asociadas a CRISPR/genética , Edición Génica , Endonucleasas/metabolismo , Endonucleasas/genética , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Endodesoxirribonucleasas/metabolismo , Endodesoxirribonucleasas/genética , Reparación del ADN por Unión de Extremidades , División del ADN , Factores de Transcripción/metabolismo , Factores de Transcripción/genética
2.
Int Orthop ; 48(5): 1133-1138, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38430224

RESUMEN

PURPOSE: Whether photographs included in the operative report of knee arthroscopies can make the surgeon liable in the event of a legal investigation remains unknown. The main objective of this study was to establish inter-observer reliability in determining the presence or absence of lesions of the cartilage, meniscus and anterior cruciate ligament (ACL). Secondary objective was to assess the inter-observer reliability in classifying lesions. METHOD: A retrospective observational study was conducted in a continuous serie of 60 patients who underwent knee arthroscopy from the same operator. The photographs of each patient's operative report were presented separately to three experts, blinded to each other. Each expert had to decide on the presence or absence of injuries to the following structures: meniscal, cartilage and ACL and then, classify it. Primary and secondary endpoints were evaluated using the Fleiss' kappa index. RESULTS: Inter-observer reliability for lesion detection was between 0.4 and 0.61 for all structures with three exceptions: for cartilage, it was low (0.15) at the lateral tibial plateau and poor (-0.01) at the external condyle. On the contrary, the concordance was almost perfect (0.8) for the ACL. For classifying cartilaginous and meniscal lesions, inter-observer reliability was poor (from 0.03 to 0.14), except for at the lateral meniscus (0.65). CONCLUSION: Inter-observer reliability of arthroscopic knee diagnoses is poor when photographs alone are used. In the event of a legal investigation following knee arthroscopy, the photographs included in the operative report should not be used alone to hold the surgeon liable.


Asunto(s)
Lesiones del Ligamento Cruzado Anterior , Lesiones de Menisco Tibial , Humanos , Lesiones del Ligamento Cruzado Anterior/diagnóstico , Lesiones del Ligamento Cruzado Anterior/cirugía , Lesiones del Ligamento Cruzado Anterior/complicaciones , Artroscopía/efectos adversos , Reproducibilidad de los Resultados , Lesiones de Menisco Tibial/diagnóstico por imagen , Lesiones de Menisco Tibial/cirugía , Articulación de la Rodilla/cirugía , Meniscos Tibiales/cirugía , Estudios Retrospectivos
3.
Skeletal Radiol ; 2023 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-38078927

RESUMEN

Knee popping is a frequent symptom among knee disorders which requires further investigation in case of a recent evolution of the symptom or pathological associated ones. This article reports a rare presentation of pigmented villonodular synovitis (PVNS), identified as the cause of knee popping symptoms, by performing MRI sequences at various degrees of knee flexion for a patient complaining from a gradual onset of knee popping, occurring when bending the knee over 120° of flexion. MRI sequences were performed just before the popping occurs (flexion 90°) and right after it had occurred (flexion 120°). The latter confirmed the origin of the symptom as the lesion moved forward, passing brutally through the interstice between the PCL and the ACL at 120° of flexion, explaining the popping. Treatment decision was to perform an arthroscopic resection of the lesion. Diagnosis of isolated PVNS was confirmed after anatomopathological analysis.

4.
Nucleic Acids Res ; 51(21): 11732-11747, 2023 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-37870477

RESUMEN

The classical Non-Homologous End Joining (c-NHEJ) pathway is the predominant process in mammals for repairing endogenous, accidental or programmed DNA Double-Strand Breaks. c-NHEJ is regulated by several accessory factors, post-translational modifications, endogenous chemical agents and metabolites. The metabolite inositol-hexaphosphate (IP6) stimulates c-NHEJ by interacting with the Ku70-Ku80 heterodimer (Ku). We report cryo-EM structures of apo- and DNA-bound Ku in complex with IP6, at 3.5 Å and 2.74 Å resolutions respectively, and an X-ray crystallography structure of a Ku in complex with DNA and IP6 at 3.7 Å. The Ku-IP6 interaction is mediated predominantly via salt bridges at the interface of the Ku70 and Ku80 subunits. This interaction is distant from the DNA, DNA-PKcs, APLF and PAXX binding sites and in close proximity to XLF binding site. Biophysical experiments show that IP6 binding increases the thermal stability of Ku by 2°C in a DNA-dependent manner, stabilizes Ku on DNA and enhances XLF affinity for Ku. In cells, selected mutagenesis of the IP6 binding pocket reduces both Ku accrual at damaged sites and XLF enrolment in the NHEJ complex, which translate into a lower end-joining efficiency. Thus, this study defines the molecular bases of the IP6 metabolite stimulatory effect on the c-NHEJ repair activity.


Asunto(s)
Proteínas de Unión al ADN , Ácido Fítico , Animales , ADN/metabolismo , Roturas del ADN de Doble Cadena , Reparación del ADN por Unión de Extremidades , Proteínas de Unión al ADN/genética , Autoantígeno Ku/metabolismo , Mamíferos/genética , Humanos
5.
Arthrosc Tech ; 11(7): e1359-e1365, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35936848

RESUMEN

Anterior cruciate ligament (ACL) rupture is a common affliction in the athletic population. In pediatric patients, the immature skeleton with active growth plates is an issue that makes ACL reconstruction surgery technically challenging. The rerupture rate after ACL reconstruction is higher in the pediatric population than in the adult population. The addition of anterolateral ligament (ALL) reconstruction has been shown to be an effective way to reduce the rate of graft rupture and to control rotatory instability (pivot shift). Therefore, it appears necessary to combine ACL and ALL reconstruction in the pediatric population. We describe the surgical steps for combined ACL and ALL reconstruction adapted for young patients with active growth plates.

6.
ACS Org Inorg Au ; 2(3): 252-260, 2022 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-36855468

RESUMEN

We describe a series of new chalcogen-bonded cocrystals featuring 1,2-bis(selenocyanatomethyl)benzene (DSN) and 1,2,4,5-tetrakis(selenocyanatomethyl)-benzene (TSN) as the donor moieties and a variety of Lewis bases such as onium halides, N-oxides, and pyridine-containing heterocycles as the acceptors. Single-crystal X-ray diffraction demonstrates that, in every case, the selenocyanates consistently interact with the acceptor molecules through strong and directional Se···X chalcogen-bonds (ChBs) (X = halides, oxygen, and nitrogen). 77Se solid-state nuclear magnetic resonance spectroscopy was applied to measure selenium chemical shift tensor magnitudes and to explore potential correlations between these tensor elements and the local ChB geometry. In every case, the isotropic 77Se chemical shift decreases, and the chemical shift tensor span increases upon cocrystallization of DSN with the various ChB acceptors. This work contributes to a growing body of knowledge concerning the predictability and robustness of chalcogen bonds in crystal engineering as well as the NMR response to the establishment of chalcogen bonds. In particular, among the systems studied here, highly linear chalcogen bonds are formed exclusively at the stronger σ-hole of each and every selenium atom regardless of the size, charge, or denticity of the electron donor moiety.

7.
Cancer Rep (Hoboken) ; 5(7): e1531, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-34409769

RESUMEN

BACKGROUND: COVID-19 changed the way we practice oncology in multiple ways. Because most cancer patients are comorbid or immunocompromised, we are trying as much as possible to reduce their risk of infection. Marginal just 2 years ago, telemedicine quickly became preeminent with the pandemic to reduce hospital exposure. However, using only virtual visits in oncology patients risk delaying cancer diagnosis or the identification of a complication. CASE SERIES: We present here four cases where a serious medical problem evident on physical exam was overlooked during a virtual visit. Two of our patients experienced a delay in cancer diagnosis thus putting them at risk of local or distant spread. The two others were established oncology patients where a serious medical complication was missed on a virtual visit. CONCLUSIONS: Now more than a year into the pandemic, telemedicine has clearly been a useful tool by limiting unnecessary hospital visits. Yet, as our cases illustrate, its use in oncology without clear boundary can undermine the quality of care. Now that effective vaccines are reducing the transmission and the severity of infection, most oncology patients can be evaluated by a real-time visit.


Asunto(s)
COVID-19 , Neoplasias , Telemedicina , COVID-19/epidemiología , Humanos , Neoplasias/diagnóstico , Neoplasias/terapia , Pandemias/prevención & control , SARS-CoV-2
8.
Vaccine ; 39(41): 6074-6080, 2021 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-34531082

RESUMEN

OBJECTIVE: We determined secular changes in the incidence of hospitalizations due to herpes zoster (HZh) and assessed the validity of HZ International Classification of Diseases (ICD) code algorithms for identifying HZh in a region of Quebec, Canada. METHODS: We performed a validation study as part of a retrospective cohort study of adult HZ patients hospitalized at Centre Hospitalier Universitaire de Sherbrooke during 2000-2017. Cases were identified using ICD codes from an inpatient administrative database. HZ cases identified by ICD-9 (053.xx) and ICD-10 (B02.x) codes were chart-confirmed, and performance characteristics of ICD code algorithms were calculated (positive predictive value [PPV] and sensitivity). RESULTS: Overall, 1314 hospitalizations with HZ diagnosis (HZh) with or without complications were identified during 2000-2017. Among the hospitalizations, 526 (44.4%) were due to active HZ disease or a complication related to a recent or previous HZ episode. These hospitalizations were due to active disease at the time of admission (340/526, 64.6%), HZ that developed during hospitalization (120/526, 22.8%), or a complication directly related to a recent or previous HZ episode (66/526, 12.6%). PPV was significantly higher when HZ was the primary diagnosis (276/310, 89%, 95% confidence interval [CI]: 85-92%) than when HZ was a secondary diagnosis (254/928, 27%, 95% CI: 25-30%) (p < 0.0001), and the PPV of a first secondary diagnosis (84/140, 60.0%, 95% CI: 51.3-68.2%) was higher than that of other secondary diagnoses (203/794, 25.6%, 95% CI: 22.6-28.8%) (p < 0.0001). An algorithm combining ICD codes and antiviral usage demonstrated the best sensitivity (86.3%, 95% CI: 83.1-89.1%) and PPV to identify HZh (100%, 95% CI: 99.2-100%). Poisson regression revealed no significant changes in HZh over time (incidence rate ratio: 0.98, 95% CI: 0.92-1.04%; p = 0.5). CONCLUSION: HZh incidence was stable over time. Prescription of antivirals might be a useful addition to ICD codes to identify HZh cases from administrative databases.


Asunto(s)
Herpes Zóster , Clasificación Internacional de Enfermedades , Adulto , Algoritmos , Bases de Datos Factuales , Herpes Zóster/diagnóstico , Herpes Zóster/epidemiología , Hospitalización , Humanos , Quebec/epidemiología , Estudios Retrospectivos
9.
Orthop Traumatol Surg Res ; 107(6): 102995, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34198006

RESUMEN

The strategy for surgical treatment of chronic ankle instability is becoming increasingly refined. In instances of isolated symptomatic non-repairable anterior talofibular ligament (ATFL) injury, there is a surgical indication for isolated ATFL reconstruction. However, we feel that the typical gracilis tendon graft is not always appropriate. Interest in using the plantaris tendon as a graft has picked up since a biomechanics study found the tensile strength of a quadrupled plantaris tendon is comparable to that of the ATFL. Here, we describe an original arthroscopic technique for isolated ATFL reconstruction using a quadrupled plantaris tendon (PT4) graft.


Asunto(s)
Traumatismos del Tobillo , Inestabilidad de la Articulación , Ligamentos Laterales del Tobillo , Traumatismos del Tobillo/diagnóstico por imagen , Traumatismos del Tobillo/cirugía , Articulación del Tobillo/diagnóstico por imagen , Articulación del Tobillo/cirugía , Humanos , Inestabilidad de la Articulación/cirugía , Ligamentos Laterales del Tobillo/cirugía , Tendones/cirugía
10.
Orthop Traumatol Surg Res ; 106(3): 459-463, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32019734

RESUMEN

BACKGROUND: Few data are available on the 20-year outcomes of anterior cruciate ligament (ACL) reconstruction. The purpose of this study was to assess the prevalence and risk factors of knee osteoarthritis at least 20 years after ACL reconstruction. HYPOTHESIS: Factors associated with progression to knee osteoarthritis include meniscal lesions, level of physical activity, injury-to-surgery time, body mass index, residual laxity, tunnel position and cartilage injury. MATERIAL AND METHODS: One hundred and eighty two patients were included in a multicentre retrospective study conducted in the setting of a SoFCOT symposium. Females contributed two-thirds of the study population. ACL reconstruction was performed arthroscopically in 82% of cases, and a bone-patellar tendon-bone transplant was used in 92.8% of cases. Mean age at surgery was 26±7years. Clinical outcomes were assessed based on the objective and subjective IKDC scores and on the KOOS. Radiographic evidence of osteoarthritis was classified according to the IKDC. Factors evaluated for their ability to predict progression to osteoarthritis included age, sex, body mass index, level of physical activity, injury-to-surgery time, meniscectomy, cartilage injury, tunnel position and residual laxity. RESULTS: At last follow-up, the objective IKDC score was A (normal) for 48%, B for 35%, and C or D for 17% of the knees. The mean subjective IKDC score was 82.7±13.1. Moderate-to-severe osteoarthritis was present in 29% of cases. The following risk factors for osteoarthritis were identified: medial or lateral meniscectomy, residual laxity, age >30years at surgery, and engaging in a pivoting sport. Meniscectomy was a major contributor to the development of osteoarthritis (17% of knees without vs. 46% with meniscectomy). Finally, the ACL re-tear rate was 13%. CONCLUSION: ACL reconstruction provides satisfactory knee stability. The risk of subsequent osteoarthritis depends chiefly on the status of the menisci. Residual laxity is also associated with the development of osteoarthritis. LEVEL OF EVIDENCE: IV, retrospective cohort study.


Asunto(s)
Lesiones del Ligamento Cruzado Anterior , Reconstrucción del Ligamento Cruzado Anterior , Osteoartritis de la Rodilla , Adulto , Lesiones del Ligamento Cruzado Anterior/epidemiología , Lesiones del Ligamento Cruzado Anterior/cirugía , Femenino , Estudios de Seguimiento , Humanos , Articulación de la Rodilla/cirugía , Osteoartritis de la Rodilla/epidemiología , Osteoartritis de la Rodilla/etiología , Osteoartritis de la Rodilla/cirugía , Estudios Retrospectivos
11.
Arthritis Res Ther ; 22(1): 5, 2020 01 08.
Artículo en Inglés | MEDLINE | ID: mdl-31915059

RESUMEN

OBJECTIVE: To describe successful therapeutic strategies in statin-induced anti-HMGCR myopathy. METHODS: Retrospective data from a cohort of 55 patients with statin-induced anti-HMGCR myopathy, sequentially stratified by the presence of proximal weakness, early remission, and corticosteroid and IVIG use at treatment induction, were analyzed for optimal successful induction and maintenance of remission strategies. RESULTS: A total of 14 patients achieved remission with a corticosteroid-free induction strategy (25%). In 41 patients treated with corticosteroids, only 4 patients (10%) failed an initial triple steroid/IVIG/steroid-sparing immunosuppressant (SSI) induction strategy. Delay in treatment initiation was independently associated with lower odds of successful maintenance with immunosuppressant monotherapy (OR 0.92, 95% CI 0.85 to 0.97, P = 0.015). While 22 patients (40%) presented with normal strength, only 9 had normal strength at initiation of treatment. CONCLUSION: While corticosteroid-free treatment of anti-HMGCR myopathy is now a safe option in selected cases, initial triple steroid/IVIG/SSI was very efficacious in induction. Delays in treatment initiation and, as a corollary, delays in achieving remission decrease the odds of achieving successful maintenance with an SSI alone. Avoiding such delays, most notably in patients with normal strength, may reset the natural history of anti-HMGCR myopathy from a refractory entity to a treatable disease.


Asunto(s)
Enfermedades Autoinmunes/inducido químicamente , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Inmunosupresores/uso terapéutico , Miositis/inducido químicamente , Miositis/etiología , Corticoesteroides/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades Autoinmunes/tratamiento farmacológico , Femenino , Humanos , Hidroximetilglutaril-CoA Reductasas/inmunología , Inmunoglobulinas Intravenosas/uso terapéutico , Quimioterapia de Inducción/métodos , Quimioterapia de Mantención/métodos , Masculino , Persona de Mediana Edad , Miositis/inmunología , Estudios Retrospectivos
12.
ChemistryOpen ; 8(11): 1328-1336, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31692837

RESUMEN

The halogen bond has previously been explored as a versatile tool in crystal engineering and anion coordination chemistry, with mechanochemical synthetic techniques having been shown to provide convenient routes towards cocrystals. In an effort to expand our knowledge on the role of halogen bonding in anion coordination, here we explore a series of cocrystals formed between 3-iodoethynylpyridine and 3-iodoethynylbenzoic acid with halide salts. In total, we report the single-crystal X-ray structures of six new cocrystals prepared by mechanochemical ball milling, with all structures exhibiting C≡C-I⋅⋅⋅X- (X=Cl, Br) halogen bonds. Whereas cocrystals featuring a pyridine group favoured the formation of discrete entities, cocrystals featuring a benzoic acid group yielded an alternation of halogen and hydrogen bonds. The compounds studied herein were further characterized by 13C and 31P solid-state nuclear magnetic resonance, with the chemical shifts offering a clear and convenient method of identifying the occurrence of halogen bonding, using the crude product obtained directly from the mechanochemical ball milling. Whereas the 31P chemical shifts were quickly able to identify the occurrence of cocrystallization, 13C solid-state NMR was diagnostic of both the occurrence of halogen bonding and of hydrogen bonding.

13.
ChemistryOpen ; 8(11): 1327, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31692897

RESUMEN

Invited for this month's cover picture is the group of Professor David Bryce at the University of Ottawa. The cover picture shows a stylized depiction of the mechanochemical halogen-bond induced cocrystallization of 3-iodoethynylpyridine with tetraphenylphosphonium bromide. Read the full text of their Full Paper at 10.1002/open.201900194.

14.
Am J Sports Med ; 46(12): 2842-2850, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30199646

RESUMEN

BACKGROUND: Anterior cruciate ligament (ACL) reconstruction is important to prevent knee osteoarthritis. Neither of the 2 most common graft techniques-the patellar tendon (PT) or hamstring tendon (HS) graft-has demonstrated superiority in terms of the long-term osteoarthritis rate. HYPOTHESIS: Based on the International Knee Documentation Committee (IKDC) radiographic grading system, PT grafts decrease the incidence of osteoarthritis by providing better knee stability as compared with HS grafts over 12 years of follow-up. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: All adults with a first ACL rupture who underwent surgery with a PT or HS graft technique between January 2002 and December 2003 were included in the 2014 French Society of Orthopedic Surgery and Traumatology Symposium database. Baseline characteristics were collected. The primary endpoint was the occurrence of moderate to severe osteoarthritis in each group. The secondary endpoints included clinical subjective evaluations by the IKDC score and Knee injury and Osteoarthritis Outcome Score. To control the differences in baseline characteristics, the data were analyzed with propensity score matching. RESULTS: In the cohort, 541 patients from 18 centers were included: 311 PT and 230 HS ACL reconstructions. The baseline characteristics were similar after inverse probability weighting treatment (IPWT). The occurrence of osteoarthritis was similar after IPWT (19.3% for PT and 19.6% for HS, P = .94). Age at surgery >29 years and IKDC osteoarthritis stage B at the index surgery were identified as risk factors for moderate to severe osteoarthritis. Most functional outcomes were significantly higher in the HS group; however, the difference between groups remained <10 points. Of the 106 patients who needed a medial meniscectomy, the proportion of patients with moderate to severe osteoarthritis was much higher in the HS group (43.5% vs 18.3%, P = .006). However, after IPWT, the difference was not statistically significant. CONCLUSION: At 12 years of follow-up, neither graft technique was superior to the other in terms of the rate of osteoarthritis.


Asunto(s)
Reconstrucción del Ligamento Cruzado Anterior/métodos , Tendones Isquiotibiales/trasplante , Osteoartritis de la Rodilla/etiología , Ligamento Rotuliano/trasplante , Adulto , Reconstrucción del Ligamento Cruzado Anterior/estadística & datos numéricos , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Osteoartritis de la Rodilla/cirugía , Adulto Joven
15.
Knee Surg Sports Traumatol Arthrosc ; 26(6): 1838-1844, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28251263

RESUMEN

PURPOSE: High tibial osteotomy (HTO) is used to treat young and active patients with knee osteoarthritis (OA) and varus deformity. The medial compartment OA alters the patients' gait. METHODS: A prospective study was carried out in 21 consecutive patients operated for HTO due to knee OA with varus deformity. There were 14 men and 7 women, with a median age of 51.9 years (38-64). Their gait was analyzed preoperatively and at 1 year postoperatively, and compared to a healthy control group. Clinical assessment (KOOS, WOMAC, Lysholm, and SF-36 scores) was also performed preoperatively and postoperatively. RESULTS: Patients with medial compartment OA had altered gait relative to the control population. Their walking speed was slower, step length was shorter, and single-leg stance time was shorter, while the double-leg stance time was longer (P < 0.001). Step width was not different between the two groups preoperatively (n.s.), but it was wider in the patient group postoperatively (P = 0.003). There were no differences in the patients' gait parameters before and after the osteotomy (n.s.). However, there was an improved perception of walking so that it is no longer different from controls (n.s.). The KOOS, WOMAC, Lysholm and SF-36 scores improved after HTO. The preoperative median of 7° varus (1-11) was corrected to 3° valgus (0-6). CONCLUSION: Medial compartment OA with varus deformity leads to gait modifications. HTO does not alter the time-distance parameters of gait; however, patients have improved perception of their walking ability. HTO leads to excellent results for knee function, and improves quality of life without modifying the gait pattern. LEVEL OF EVIDENCE: II.


Asunto(s)
Marcha/fisiología , Genu Varum/cirugía , Articulación de la Rodilla/fisiopatología , Osteoartritis de la Rodilla/fisiopatología , Osteotomía/métodos , Tibia/cirugía , Adulto , Femenino , Genu Varum/fisiopatología , Humanos , Articulación de la Rodilla/cirugía , Masculino , Persona de Mediana Edad , Osteoartritis de la Rodilla/cirugía , Estudios Prospectivos , Calidad de Vida
16.
Int Orthop ; 42(6): 1233-1239, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-28699021

RESUMEN

PURPOSE: Cysts of the proximal tibiofibular articulation are rare and their optimal treatment remains unclear. The objective of this study was to evaluate the results and complications of the treatment of synovial ganglion cysts of the proximal tibiofibular articulation by simple excision or by excision and fusion of the proximal tibiofibular joint with a limited fibula excision. METHODS: Between January 2005 and December 2016, seven male patients with an average age of 46 years were treated for a ganglion cyst of the proximal tibiofibular articulation. Nine procedures were performed in total. Four patients underwent primary cyst excision, two underwent revision cyst excision and three underwent revision cyst excision with arthrodesis of the proximal tibiofibular joint and partial excision of the fibula (two patients underwent two procedures). RESULTS: Average follow-up was 79 months. The recurrence rate was 25% for simple cyst excision, 100% for revision cyst excision and 0% for cyst excision with arthrodesis. Average kitaoka score was 98 for simple cyst excision and 100 for cyst excision with arthrodesis (P = 0.34); resting visual analogue scores (VAS) were zero in both groups. With activity VAS was 0 for simple cyst excision and 1.6 in the arthrodesis group (P = 0.33). Two of the three arthrodesis patients went on to successful fusion. The third patient has an asymptomatic pseudarthrosis. CONCLUSION: Simple primary cyst excision has a high failure rate at 25%. Revision cyst excision without fusion failed in all cases. We therefore recommend arthrodesis with limited fibula excision.


Asunto(s)
Artrodesis/métodos , Peroné/cirugía , Ganglión/cirugía , Articulación de la Rodilla/patología , Adulto , Artrodesis/efectos adversos , Estudios de Cohortes , Humanos , Articulación de la Rodilla/cirugía , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Recurrencia , Reoperación/estadística & datos numéricos , Resultado del Tratamiento , Escala Visual Analógica
17.
Int Orthop ; 42(4): 799-804, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-28831536

RESUMEN

PURPOSE: The aim of this study was to analyse the clinical and radiographic results of 208 e-Motion® posterior cruciate-retaining, mobile bearing prostheses (BBraun-Aesculap, Tuttlingen, Germany) fitted using computer navigation, for knee osteoarthritis with a genu varum greater than 10°. METHODS: One hundred ninety-two patients were operated on with 208 e-Motion® prostheses fitted, between January 2006 and December 2011, using the OrthoPilot® computer navigation system. Average pre-operative IKS score was 70 ± 27 points (6-143) with a function score of 38 ± 20.5 (0-90) and a knee score of 32.5 ± 13 (0-63). Average flexion was 116.5° ± 13° (65-140°). Average pre-operative HKA angle was 166° ± 3° (154-169°). RESULTS: 2Results are available for 134 patients, with a total of 150 knees operated on (38 lost to follow-up and 20 deceased). Average follow-up was 104.5 months (60-116 months). On last follow-up, the average IKS was 180 ± 22 points (95-200) with 86.5 ± 16 points (25-100) for the function score and 93.5 ± 8 points (55-100) for the knee score. Knee flexion was 116° ± 10.5° (80-135°) and average HKA angle was 179° ± 2° (175-184°). The pre-operative objective was achieved in 90.5% of knees. CONCLUSION: The e-Motion® mobile bearing posterior cruciate-retaining prosthesis, fitted using computer navigation, offers excellent results after an average of 8.5 years follow-up. These results are at least equivalent, even superior, to those of the posterior-stabilised prostheses usually used for this type of deformity.


Asunto(s)
Artroplastia de Reemplazo de Rodilla/métodos , Genu Varum/cirugía , Prótesis de la Rodilla/efectos adversos , Osteoartritis de la Rodilla/cirugía , Cirugía Asistida por Computador/métodos , Adulto , Anciano , Anciano de 80 o más Años , Artroplastia de Reemplazo de Rodilla/instrumentación , Femenino , Estudios de Seguimiento , Humanos , Articulación de la Rodilla/cirugía , Masculino , Persona de Mediana Edad , Falla de Prótesis , Rango del Movimiento Articular , Resultado del Tratamiento
18.
Oncotarget ; 8(25): 40152-40168, 2017 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-27374179

RESUMEN

PARP inhibitors (PARPi), such as Olaparib, have shown promising results in high-grade serous (HGS) epithelial ovarian cancer (EOC) treatment. PARPi sensitivity has been mainly associated with homologous recombination (HR) deficiency, but clinical trials have shown that predicting actual patient response is complex. Here, we investigated gene expression microarray, HR functionality and Olaparib sensitivity of 18 different HGS EOC cell lines and demonstrate that PARPi sensitivity is not only associated with HR defects. Gene target validation show that down regulation of genes in the nucleotide excision repair (NER) and mismatch repair (MMR) pathways (ERCC8 and MLH1, respectively) increases PARPi response. The highest sensitivity was observed when genes in both the HR and either NER or MMR pathways were concomitantly down regulated. Using clinical samples, patients with these concurrent down regulations could be identified. Based on these results, a novel model to predict PARPi sensitivity is herein proposed. This model implies that the extreme responders identified in clinical trials have deficiencies in HR and either NER or MMR.


Asunto(s)
Reparación del ADN/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Ftalazinas/farmacología , Piperazinas/farmacología , Transducción de Señal/efectos de los fármacos , Carcinoma Epitelial de Ovario , Línea Celular Tumoral , Femenino , Perfilación de la Expresión Génica/métodos , Humanos , Clasificación del Tumor , Neoplasias Glandulares y Epiteliales/genética , Neoplasias Glandulares y Epiteliales/metabolismo , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Interferencia de ARN , Transducción de Señal/genética
19.
Injury ; 47(6): 1282-7, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27037028

RESUMEN

PURPOSE: Over the past 10 years, like many authors, we observed an increasing number of Moore I tibial plateau fractures related to alpine skiing for which the surgeon may face difficult choices regarding surgical approach and fixation means. Some authors have recently been suggesting a posterior approach associated to open reduction and osteosynthesis by a buttress plate. But in our knowledge there is no specific study on sports activity recovery after Moore I tibial fractures. The aim of this work was to assess sports activities and clinical outcomes after surgically treated Moore I tibial plateau fractures in an athletic population of skiers. METHODS: We conducted a prospective case series between 2012 and 2014. This included fifteen patients aged 39.6±7 years whom presented with a Moore I tibial plateau fracture during a skiing accident. 12 cases (80%) presented with an associated tibial spine fracture. Treatment consisted of a standard antero-medial approach, with a medial para patellar arthrotomy to allow direct visualisation of articular reduction and spinal fixation. Two or three 6.5mm long cancellous bone screws were placed antero-posteriorly so as to ensure perfect compression of the fracture site. Radiological and functional results were assessed by an independent observer (Lysholm-Tegner, UCLA, KOOS scores) at the longest follow-up. RESULTS: Mean follow-up was 18.2±6 months (12-28). An immediate postoperative anatomical reduction was achieved in all cases and remained stable in time. At last follow-up Lysholm mean score was 85±14 points (59-100), UCLA score was 7.3±1.6 (4-10) and Tegner score was 4.6±1.3 (3-6). Mean KOOS score was 77±15 (54-97). 87% of patients had resumed their skiing activity and 93% were satisfied or very satisfied from their post-operative surgical outcome. We observed no pseudarthrosis or secondary varus displacement. CONCLUSION: In our series 87% of patients had resumed back to their sporting activities. Surgical management of Moore I tibial plateau fractures by isolated antero-posterior screwing provides excellent clinical and radiological results. The anteromedial incision has a dual advantage of anatomical reduction, tibial spine fixation (in 80% of our cases) and posteromedial fragment reduction.


Asunto(s)
Fijación Interna de Fracturas/métodos , Fracturas Intraarticulares/cirugía , Luxaciones Articulares/cirugía , Traumatismos de la Rodilla/cirugía , Radiografía , Volver al Deporte/estadística & datos numéricos , Esquí/lesiones , Fracturas de la Tibia/cirugía , Adulto , Placas Óseas , Femenino , Estudios de Seguimiento , Curación de Fractura , Humanos , Fracturas Intraarticulares/diagnóstico por imagen , Fracturas Intraarticulares/fisiopatología , Traumatismos de la Rodilla/diagnóstico por imagen , Traumatismos de la Rodilla/fisiopatología , Masculino , Estudios Prospectivos , Recuperación de la Función , Fracturas de la Tibia/diagnóstico por imagen , Fracturas de la Tibia/fisiopatología , Resultado del Tratamiento
20.
Artículo en Inglés | MEDLINE | ID: mdl-19875315

RESUMEN

OBJECTIVES: This in vivo study was aimed at quantifying the electronic no-function rate of 2 electronic apex locators, ApexPointer and Novapex, and evaluating whether their operation is affected by the type of applied treatment, patient's age, and the type of tooth. STUDY DESIGN: A total of 209 root canals were included in this study. For each canal, the electronic length was determined and verified by radiography. Whenever the electronic device failed to provide a value, it was recorded as an electronic no-function. Experimental data were statistically tested with chi-squared through Statview. RESULTS: For both apex locators, the no-function rate remained around 15% and did not seem to be affected by the age of patients. A statistically significant relationship was found between no-function rate and retreatment (P < .05). The type of tooth had no influence on the no-function rate. CONCLUSIONS: Under the conditions of this assessment in vivo, the 2 apex locators proved to give no value in about 15% of the cases. Further investigations are necessary to clear up the links between no-function and retreatment or age.


Asunto(s)
Cavidad Pulpar/anatomía & histología , Análisis de Falla de Equipo/métodos , Tratamiento del Conducto Radicular/instrumentación , Ápice del Diente/anatomía & histología , Adolescente , Adulto , Anciano , Niño , Cavidad Pulpar/diagnóstico por imagen , Falla de Equipo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Odontometría/instrumentación , Radiografía , Reproducibilidad de los Resultados , Ápice del Diente/diagnóstico por imagen , Adulto Joven
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