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1.
Langenbecks Arch Surg ; 409(1): 197, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38913126

RESUMEN

BACKGROUND: The Swiss national union of residents and attendings (VSAO) has voiced its desire for a transition from the current 48 h work week to a 42 + 4 h work week, in which 42 h be focused on patient care with the remaining 4 h be dedicated solely to training purposes. This could potentially result in a significant decrease in surgical education time. The current study seeks to address the issues involved in its implementation as well as possible compensatory mechanisms. METHODS: This mixed methods study seeks to clearly underline the challenges associated with the implementation of a 42 + 4 h work week. First, the major stakeholders were identified and analysed via umbrella review. Thereafter, a classic stakeholder analysis was performed. Via morphological matrix, possible models for the implementation of a 42 + 4 h work week were developed and evaluated. Finally, representatives from the identified stakeholder groups were interviewed and given the opportunity to provide feedback. RESULTS: A total of 26 articles were identified by the literature search and were used to identify the major stakeholders and issues involved in the implementation of the desired work hour regulation. Overall, these showed conflicting results with regard to the effect decreased working hours would have on surgical training and patient outcomes. In the end, the morphological matrix produced three feasible and desirable models for the implementation of a 42 + 4 h work week. Each included compensatory mechanisms like auxiliary staff, reduction in administrative tasks, and a switch to EPAs. In their interviews, the stakeholders generally supported these solutions. CONCLUSION: Given the increasing emphasis on the importance of a positive work-life balance, it seems inevitable that the next few years will see the introduction of a 42 + 4 h work week in Switzerland. However, it is imperative that every effort be made to preserve the quality of training and patient care for the next generations. This will require the cooperation of all stakeholders in order to find workable solutions.


Asunto(s)
Cirugía General , Internado y Residencia , Admisión y Programación de Personal , Carga de Trabajo , Internado y Residencia/organización & administración , Suiza , Humanos , Admisión y Programación de Personal/organización & administración , Cirugía General/educación , Tolerancia al Trabajo Programado , Educación de Postgrado en Medicina , Participación de los Interesados
2.
Artículo en Inglés | MEDLINE | ID: mdl-38869659

RESUMEN

INTRODUCTION: Traumatic elbow dislocations are among the most common injuries in sport climbing. They occur most frequently in bouldering (a climbing discipline with strong upward trend often performed indoors) due to the typical low-height backward fall into crashpads. There is still no data about the functional outcome and return to sport of this typical bouldering injury. MATERIALS AND METHODS: All Patients with elbow dislocations due to a bouldering associated fall between 2011 and 2020 were identified retrospectively in our level I trauma centre. Trauma mechanisms, injury types and therapies were obtained. Follow-up was performed with an online questionnaire including sports-related effects, return to sport and the Elbow Self-Assessment Score (ESAS). RESULTS: 30 patients with elbow dislocations after bouldering accidents were identified. In 22 (73.3%) patients the injury was a simple dislocation. The questionnaire was completed by 20 patients. The leading mechanism was a low-height fall into crashpads. Surgical procedures were performed in every second patient. 18 patients (90%) reported return to bouldering after 4.7 ± 2.1 months. 12 patients (66.7%) regained their pre-injury level. Mid-/Long-term follow-up (mean 105 ± 37.5 months) showed excellent results in ESAS score (97.2 ± 3.9 points). Persistent limited range of motion or instability was reported by only 3 patients (15%). CONCLUSION: Most athletes are able to return to bouldering but only two thirds regain their pre-injury performance level in this demanding upper-extremity sport. The unique low-height trauma mechanism may create a false sense of security. Specific awareness and safety features should be placed for climbing athletes to reduce elbow injuries.

3.
Nat Commun ; 15(1): 63, 2024 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-38167404

RESUMEN

Avapritinib is the only potent and selective inhibitor approved for the treatment of D842V-mutant gastrointestinal stromal tumors (GIST), the most common primary mutation of the platelet-derived growth factor receptor α (PDGFRA). The approval was based on the NAVIGATOR trial, which revealed overall response rates of more than 90%. Despite this transformational activity, patients eventually progress, mostly due to acquired resistance mutations or following discontinuation due to neuro-cognitive side effects. These patients have no therapeutic alternative and face a dismal prognosis. Notable, little is known about this drug's binding mode and its medicinal chemistry development, which is instrumental for the development of the next generation of drugs. Against this background, we solve the crystal structures of avapritinib in complex with wild-type and mutant PDGFRA and stem cell factor receptor (KIT), which provide evidence and understanding of inhibitor binding and lead to the identification of a sub-pocket (Gα-pocket). We utilize this information to design, synthesize and characterize avapritinib derivatives for the determination of key pharmacophoric features to overcome drug resistance and limit potential blood-brain barrier penetration.


Asunto(s)
Antineoplásicos , Tumores del Estroma Gastrointestinal , Humanos , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genética , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Tumores del Estroma Gastrointestinal/genética , Tumores del Estroma Gastrointestinal/patología , Pirazoles/uso terapéutico , Pirroles/farmacología , Pirroles/uso terapéutico , Mutación , Proteínas Proto-Oncogénicas c-kit/genética , Antineoplásicos/farmacología
4.
Front Surg ; 10: 877252, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37091269

RESUMEN

Introduction: Although distal radius fractures (DRFs) are the most common fractures of the human body, there are still ongoing debates concerning the treatment for type A fractures, especially in elderly patients. In spite of good clinical outcomes, it remains unclear whether elderly patients, especially, could regain the preoperative functional level of the wrist. Therefore, we have quantified wrist function within a retrospective study design using patient-reported outcome measures (PROM) and we have analyzed the influence of age between control and patient collective and young vs. old, respectively. Patients and methods: The retrospective study included all patients with a surgically treated DRF type A and a control group of healthy patients, age and gender matched. The function of the wrist was examined by using a self-assessment questionnaire called the Munich Wrist Questionnaire (MWQ) according to the patient-related outcome measurements PROM. Results: We could enroll 110 patients and controls, and the average follow-up was 66 months. Subgroup matching induced similar age group distribution: in both groups, 7 individuals <30 years, 67 between 31 and 64 years, 29 between 65 and 79 years, and 7 individuals >80 years, were enrolled, respectively. In the fracture group, women were significantly older than men (59 ± 15 vs. 47 ± 17 (M ± SD). There was no significant difference between the control and the patient groups (96 ± 6 vs. 95 ± 7). The function was significantly different between controls and patients <30 years (100 ± 1 vs. 98 ± 2). In the control group, there was a functional difference in the age group <30 compared with 65-79 and >80 and in the age group 30-64 compared with 65-79 and >80. In the control group, the function was found to be significantly decreasing with advancing age, whereas in the patient group, this influence was absent. A correlation analysis showed a worse function with increasing age in the control group and therefore a negative correlation. In the fracture group, a similar result could not be obtained. Discussion: Age has a relevant influence on wrist function. Although the wrist function decreases significantly with aging, in the patient group, this influence is absent, and the functional results after surgery are excellent. Even elderly patients can regain their preoperative functional level.

5.
Langenbecks Arch Surg ; 408(1): 90, 2023 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-36790506

RESUMEN

BACKGROUND: Anastomotic leakages after esophagectomies continue to constitute significant morbidity and mortality. Intrathoracic anastomoses pose a high risk for mediastinitis, sepsis, and death, if a leak is not addressed timely and appropriately. However, there are no standardized treatment recommendations or algorithms as for how to treat these leakages. METHODS: The study included all patients at the University Hospital Regensburg, who developed an anastomotic leakage after esophagectomy with gastric pull-up reconstruction from 2007 to 2022. Patients receiving conventional treatment options for an anastomotic leakage (stents, drainage tubes, clips, etc.) were compared to patients receiving endoscopic vacuum-assisted closure (eVAC) therapy as their mainstay of treatment. Treatment failure was defined as cervical esophagostomy formation or death. RESULTS: In total, 37 patients developed an anastomotic leakage after esophagectomy with a gastric pull-up reconstruction. Twenty patients were included into the non-eVAC cohort, whereas 17 patients were treated with eVAC. Treatment failure was observed in 50% of patients (n = 10) in the non-eVAC cohort and in 6% of patients (n = 1) in the eVAC cohort (p < 0.05). The 90-day mortality in the non-eVAC cohort was 15% (n = 3) compared to 6% (n = 1) in the eVAC cohort. Cervical esophagostomy formation was required in 40% of cases (n = 8) in the non-eVAC cohort, whereas no patient in the eVAC cohort underwent cervical esophagostomy formation. CONCLUSION: eVAC therapy for leaking esophagogastric anastomoses appears to be superior to other treatment strategies as it significantly reduces morbidity and mortality. Therefore, we suggest eVAC as an essential component in the treatment algorithm for anastomotic leakages following esophagectomies, especially in patients with intrathoracic anastomoses.


Asunto(s)
Neoplasias Esofágicas , Terapia de Presión Negativa para Heridas , Humanos , Fuga Anastomótica/etiología , Fuga Anastomótica/cirugía , Esofagectomía/efectos adversos , Anastomosis Quirúrgica/efectos adversos , Endoscopía , Neoplasias Esofágicas/cirugía , Estudios Retrospectivos , Resultado del Tratamiento
7.
IEEE Trans Med Imaging ; 41(12): 3489-3497, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36251918

RESUMEN

Histopathology as a diagnostic mainstay for tissue evaluation is strictly a 2D technology. Combining and supplementing this technology with 3D imaging has been proposed as one future avenue towards refining comprehensive tissue analysis. To this end, we have developed a laboratory-based X-ray method allowing for the investigation of tissue samples in three dimensions with isotropic volume information. To assess the potential of our method for micro-morphology evaluation, we selected several kidney regions from three patients with cystic kidney disease, obstructive nephropathy and diabetic glomerulopathy. Tissue specimens were processed using our in-house-developed X-ray eosin stain and investigated with a commercial microCT and our in-house-built NanoCT. The microCT system provided overview scans with voxel sizes of [Formula: see text] and the NanoCT was employed for higher resolutions including voxel sizes from [Formula: see text] to 210 nm. We present a methodology allowing for a precise micro-morphologic investigation in three dimensions which is compatible with conventional histology. Advantages of our methodology are its versatility with respect to multi-scale investigations, being laboratory-based, allowing for non-destructive imaging and providing isotropic volume information. We believe, that after future developmental work this method might contribute to advanced multi-modal tissue diagnostics.


Asunto(s)
Técnicas Histológicas , Imagenología Tridimensional , Humanos , Imagenología Tridimensional/métodos , Microtomografía por Rayos X/métodos , Técnicas Histológicas/métodos , Eosina Amarillenta-(YS) , Riñón/diagnóstico por imagen
8.
Hernia ; 26(5): 1337-1345, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36138268

RESUMEN

PURPOSE: Ventral hernias are frequent and hernia repair is regularly performed by general surgeons. Emergency repair is less frequent and can be challenging. Long-term data comparing outcomes of emergency- vs. elective ventral hernia repair are scarce. METHODS: Consecutive patients undergoing emergency and elective ventral hernia repair at our institution were prospectively entered in our HerniaMed database between August 2013 and February 2020. Patients were contacted after 1 and 5 years to assess long-term complications. Risk factors for emergency repair and hernia recurrence were assessed by univariate and multivariate analysis. RESULTS: We included 1307 patients. Emergency and elective hernia repair were performed in 11% and 89% of patients with 1-year follow-up rates of 94% and 92%. Female gender, BMI > 40 kg/m2, ASA class 3 and 4, large size umbilical herniation (> 4 cm) and epigastric herniation were more frequent in emergency hernia repair. Binary logistic regression analysis identified emergency repair and smoking as predictors of recurrence (Odds ratio: 4.04 and 95% confidence interval: 1.67-14.21, p = 0.004; Odds ratio: 2.94 and 95% confidence interval: 1.33-9.15, p = 0.011). Furthermore, female gender and significant comorbidity (ASA class 3 and 4) were risk factors for emergency repair (Odds ratio: 1.98 and 95% confidence interval: 01.05-3.74, p = 0.034; Odds ratio: 3.54 and 95% confidence interval: 1.79-6.98, p < 0.001). CONCLUSIONS: Emergency repair and smoking predicted hernia recurrence. Females and highly comorbid patients are at increased risk for emergency repair and should be prioritized for early elective hernia repair.


Asunto(s)
Hernia Ventral , Herniorrafia , Fumar , Procedimientos Quirúrgicos Electivos/efectos adversos , Femenino , Hernia Ventral/epidemiología , Hernia Ventral/etiología , Hernia Ventral/cirugía , Herniorrafia/efectos adversos , Humanos , Recurrencia , Estudios Retrospectivos , Fumar/efectos adversos , Fumar/epidemiología , Mallas Quirúrgicas
9.
Langenbecks Arch Surg ; 407(7): 2755-2762, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35896813

RESUMEN

BACKGROUND: Revision surgeries in patients with failed gastric banding including band removal are increasingly necessary. However, long-term outcomes after band removal alone are unsatisfactory due to weight regain and limited improvement in quality of life. This study aimed to report mid-term quality of life outcomes after gastric band removal and single-stage conversion to Roux-en-Y gastric bypass. METHODS: Data of 108 patients who underwent conversion surgery from 2011 to 2017 were extracted from a prospective database and retrospectively analyzed. During follow-up visits, physical and laboratory data as well as quality of life questionnaires were obtained. RESULTS: Postoperative mean Moorehead score increased significantly after 1 year (1.62 ± 0.86, p < 0.001) and after 5 years (1.55 ± 0.84, p < 0.001) compared to baseline values (0.72 ± 1.1). The mean follow-up time was 53 months. Moorehead scores at 1, 2, and 5 years postoperative were available in 75% (n = 81), 71% (n = 77), and 42% (n = 45) of cases, respectively. Mixed ANOVA analysis showed a significantly superior increase in Moorehead score in males (p = 0.024). No other significant predictors were identified. Lasting BMI reduction (- 4.6 to 33.0 ± 6.7 kg/m2, p < 0.001) and weight loss (- 12.9% (- 13.6 kg), p < 0.001) 5 years after conversion surgery were seen. Postoperative complications occurred in 35% (n = 38) of patients with a re-operation rate of 30.5% (n = 33). CONCLUSION: The current study shows that band removal with single-stage gastric bypass in patients with failed gastric banding leads to a lasting improvement in quality of life and may be the rescue procedure of choice in this setting.


Asunto(s)
Derivación Gástrica , Gastroplastia , Laparoscopía , Obesidad Mórbida , Masculino , Humanos , Derivación Gástrica/métodos , Gastroplastia/efectos adversos , Gastroplastia/métodos , Calidad de Vida , Obesidad Mórbida/cirugía , Obesidad Mórbida/complicaciones , Estudios Retrospectivos , Estudios de Cohortes , Laparoscopía/métodos , Reoperación , Resultado del Tratamiento
10.
Ophthalmologie ; 119(7): 714-720, 2022 Jul.
Artículo en Alemán | MEDLINE | ID: mdl-35084552

RESUMEN

BACKGROUND: Medical data should be evaluated with respect to quality management, for scientific and research purposes on the basis of registries. These data are stored in the EMR in an unstructured way and are not suitable for automatic evaluation. METHOD: The EMR tomedo (Zollsoft/Jena) and the PACS of FORUM (Zeiss/Oberkochen) manage personal, medical and image data for cataract surgery. New developed input masks gather data from diagnostic tools direct in a structured way. These data are automatically extracted by an ETL process and are stored in our data warehouse. Via Excel specific data can be selected and displayed in the dashboard. All medical data are structured and stored electronically. Few data are entered manually and most of the data are entered by pull-down menus or taken over directly from diagnostic equipment. RESULTS: A total of 2816 cataract surgeries of 1844 patients were selected for a first analysis. Results of IOL type distribution in relation to the patients and to the surgeons are displayed as well as prediction error of refraction for the 4 different groups of IOLs. DISCUSSION: Structured data input into the EMR (electronic medical record) makes data for automatic extraction available thus reducing input errors or confounding data. The result is a high quality of data sets. Input of epidemiological and general medical data also helps to perform health services research. These registry data represent better information for real live data than data from clinical trials. Bureaucratic hurdles in Germany prevent the use of registry data.


Asunto(s)
Extracción de Catarata , Catarata , Catarata/diagnóstico , Registros Electrónicos de Salud , Humanos , Refracción Ocular , Sistema de Registros
11.
Arch Orthop Trauma Surg ; 142(7): 1589-1595, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34331580

RESUMEN

INTRODUCTION: The object of this study was to evaluate the primary stability of tibial interference screw (IFS) fixation in single-stage revision surgery of the anterior cruciate ligament (ACL) in the case of recurrent instability after ACL repair with dynamic intraligamentary stabilization (DIS), dependent on the implant position during DIS. MATERIALS AND METHODS: Tibial aperture fixation in ACL reconstruction (ACL-R) was performed in a porcine knee model using an IFS. Native ACL-R was performed in the control group (n = 15). In the intervention groups DIS and subsequent implant removal were performed prior to single-stage revision ACL-R. A distance of 20 mm in group R-DIS1 (n = 15) and 5 mm in group R-DIS2 (n = 15) was left between the joint line and the implant during DIS. Specimens were mounted in a material-testing machine and load-to-failure was applied in a worst-case-scenario. RESULTS: Load to failure was 454 ± 111 N in the R-DIS1 group, 154 ± 71 N in the R-DIS2 group and 405 ± 105 N in the primary ACL-R group. Load-to-failure, stiffness and elongation of the group R-DIS2 were significantly inferior in comparison to R-DIS1 and ACL-R respectively (p < 0.001). No significant difference was found between load-to-failure, stiffness and elongation of R-DIS1 and the control group. CONCLUSION: Primary stability of tibial aperture fixation in single-stage revision ACL-R in case of recurrent instability after DIS depends on monobloc position during ACL repair. Primary stability is comparable to aperture fixation in primary ACL-R, if a bone stock of 20 mm is left between the monobloc and the tibial joint line during the initial procedure.


Asunto(s)
Lesiones del Ligamento Cruzado Anterior , Reconstrucción del Ligamento Cruzado Anterior , Animales , Ligamento Cruzado Anterior/cirugía , Lesiones del Ligamento Cruzado Anterior/cirugía , Reconstrucción del Ligamento Cruzado Anterior/métodos , Tornillos Óseos , Humanos , Articulación de la Rodilla/cirugía , Porcinos
13.
Arch Orthop Trauma Surg ; 142(11): 3247-3254, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34432097

RESUMEN

INTRODUCTION: Surgical treatment of complex humeral head fractures in the elderly is challenging due to osteoporotic bone, comorbidities and reduced compliance. The treatment strategy (reconstruction versus replacement) should allow for a functional aftercare and result in a high patient satisfaction. Major complications leading to surgical revision are crucial and should be avoided. The purpose of this study was to analyse the major complication rate leading to surgical revision and the patient-based outcome in complex humeral head fractures of the elderly population treated either using locking plate fixation (LCP) or reversed total shoulder arthroplasty (rTSA). MATERIALS AND METHODS: All patients older than 65 years surgically treated due to a four-part fracture of the proximal humerus between 2003 and 2015 were enrolled in our retrospective study. Major complications and revision rates were recorded and functional outcome was assessed using the Munich Shoulder Questionnaire (MSQ) allowing for qualitative self-assessment of the Shoulder Pain and Disability Index (SPADI), of the Disability of the Arm, Shoulder and Hand (DASH) score and of the Constant Score. RESULTS: A cohort of 103 patients with a mean age of 73.4 ± 6.2 years suffering from four-part fractures of the humeral head were enrolled. 63 patients were treated using the LCP fixation compared to 40 rTSAs. There were no significant differences in the patient-reported functional outcome. The revision rate was significantly higher in the LCP group (10/63; 15.9%) compared to the rTSA group (1/40; 2.5%). Reasons for revision were avascular head necrosis, cut-out of screws, secondary dislocation of the greater tuberosity and hypersensitivity to metal. CONCLUSIONS: Reversed total shoulder arthroplasty and locking plate fixation are both established surgical procedures for the management of complex proximal humerus fractures in the elderly leading to similar functional results. However the revision rate in the rTSA group was significantly lower. Primary rTSA should, therefore, be favoured in multimorbid elderly patients with an increased complication risk to avoid repeated anaesthesia.


Asunto(s)
Artroplastía de Reemplazo de Hombro , Fracturas del Hombro , Anciano , Artroplastía de Reemplazo de Hombro/métodos , Placas Óseas/efectos adversos , Fijación Interna de Fracturas/métodos , Humanos , Cabeza Humeral/cirugía , Estudios Retrospectivos , Fracturas del Hombro/cirugía , Resultado del Tratamiento
15.
Sci Rep ; 11(1): 20672, 2021 10 19.
Artículo en Inglés | MEDLINE | ID: mdl-34667240

RESUMEN

Peri-implantitis may result in the loss of dental implants. Cold atmospheric pressure plasma (CAP) was suggested to promote re-osseointegration, decrease antimicrobial burden, and support wound healing. However, the long-term risk assessment of CAP treatment in the oral cavity has not been addressed. Treatment with two different CAP devices was compared against UV radiation, carcinogen administration, and untreated conditions over 12 months. Histological analysis of 406 animals revealed that repeated CAP exposure did not foster non-invasive lesions or squamous cell carcinoma (SCCs). Carcinogen administration promoted non-invasive lesions and SCCs. Molecular analysis by a qPCR screening of 144 transcripts revealed distinct inflammatory profiles associated with each treatment regimen. Interestingly, CAP treatment of carcinogen-challenged mucosa did not promote but instead left unchanged or reduced the proportion of non-invasive lesions and SCC formation. In conclusion, repeated CAP exposure of murine oral mucosa was well tolerated, and carcinogenic effects did not occur, motivating CAP applications in patients for dental and implant treatments in the future.


Asunto(s)
Carcinogénesis/efectos de los fármacos , Carcinógenos/administración & dosificación , Mucosa Bucal/efectos de los fármacos , Gases em Plasma/administración & dosificación , Animales , Antibacterianos/farmacología , Presión Atmosférica , Implantes Dentales/efectos adversos , Inflamación/inducido químicamente , Masculino , Ratones , Oseointegración/efectos de los fármacos , Periimplantitis/inducido químicamente , Propiedades de Superficie/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos
16.
Microbiol Spectr ; 9(1): e0014521, 2021 09 03.
Artículo en Inglés | MEDLINE | ID: mdl-34106579

RESUMEN

Upon Kaposi's Sarcoma-associated herpesvirus (KSHV) lytic reactivation, rapid and widespread amplification of viral DNA (vDNA) triggers significant nuclear reorganization. As part of this striking shift in nuclear architecture, viral replication compartments are formed as sites of lytic vDNA production along with remarkable spatial remodeling and the relocalization of cellular and viral proteins. These viral replication compartments house several lytic gene products that coordinate viral gene expression, vDNA replication, and nucleocapsid assembly. The viral proteins and mechanisms that regulate this overhaul of the nuclear landscape during KSHV replication remain largely unknown. KSHV's ORF20 is a widely conserved lytic gene among all herpesviruses, suggesting it may have a fundamental contribution to the progression of herpesviral infection. Here, we utilized a promiscuous biotin ligase proximity labeling method to identify the proximal interactome of ORF20, which includes several replication-associated viral proteins, one of which is ORF59, the KSHV DNA processivity factor. Using coimmunoprecipitation and immunofluorescence assays, we confirmed the interaction between ORF20 and ORF59 and tracked the localization of both proteins to KSHV replication compartments. To further characterize the function of ORF20, we generated an ORF20-deficient KSHV and compared its replicative fitness to that of wild-type virus. Virion production was significantly diminished in the ORF20-deficient virus as observed by supernatant transfer assays. Additionally, we tied this defect in viable virion formation to a reduction in viral late gene expression. Lastly, we observed an overall reduction in vDNA replication in the ORF20-deficient virus, implying a key role for ORF20 in the regulation of lytic replication. Taken together, these results capture the essential role of KSHV ORF20 in progressing viral lytic infection by regulating vDNA replication alongside other crucial lytic proteins within KSHV replication compartments. IMPORTANCE Kaposi's Sarcoma-associated herpesvirus (KSHV) is a herpesvirus that induces lifelong infection, and as such, its lytic replication is carefully controlled to allow for efficient dissemination from its long-term reservoir and for the spread of the virus to new hosts. Viral DNA replication involves many host and viral proteins, coordinating both in time and space to successfully progress through the viral life cycle. Yet, this process is still not fully understood. We investigated the role of the poorly characterized viral protein ORF20, and through proximity labeling, we found that ORF20 interacts with ORF59 in replication compartments and affects DNA replication and subsequent steps of the late viral life cycle. Collectively, these results provide insights into the possible contribution of ORF20 to the complex lytic DNA replication process and suggest that this highly conserved protein may be an important modulator of this key viral mechanism.


Asunto(s)
Infecciones por Herpesviridae/virología , Herpesvirus Humano 8/metabolismo , Proteínas Virales/metabolismo , Activación Viral , Replicación Viral , Replicación del ADN , Regulación Viral de la Expresión Génica , Herpesvirus Humano 8/genética , Humanos , Unión Proteica , Proteínas Virales/genética
17.
Breast Cancer Res Treat ; 187(2): 437-446, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33606158

RESUMEN

PURPOSE: Some studies have indicated age-specific differences in quality of life (QoL) among breast cancer (BC) patients. The aim of this study was to compare patient-reported outcomes after conventional and oncoplastic breast surgery in two distinct age groups. METHODS: Patients who underwent oncoplastic and conventional breast surgery for stage I-III BC, between 6/2011-3/2019, were identified from a prospectively maintained database. QoL was prospectively evaluated using the Breast-Q questionnaire. Comparisons were made between women < 60 and ≥ 60 years. RESULTS: One hundred thirty-three patients were included. Seventy-three of them were ≥ 60 years old. 15 (20.5%) of them received a round-block technique (RB) / oncoplastic breast-conserving surgeries (OBCS), 10 (13.7%) underwent nipple-sparing mastectomies (NSM) with deep inferior epigastric perforator flap (DIEP) reconstruction, 23 (31.5%) underwent conventional breast-conserving surgeries (CBCS), and 25 (34.2%) received total mastectomy (TM). Sixty patients were younger than 60 years, 15 (25%) thereof received RB/OBCS, 22 (36.7%) NSM/DIEP, 17 (28.3%) CBCS, and 6 (10%) TM. Physical well-being chest and psychosocial well-being scores were significantly higher in older women compared to younger patients (88.05 vs 75.10; p < 0.001 and 90.46 vs 80.71; p = 0.002, respectively). In multivariate linear regression, longer time intervals had a significantly positive effect on the scales Physical Well-being Chest (p = 0.014) and Satisfaction with Breasts (p = 0.004). No significant results were found concerning different types of surgery. CONCLUSION: Our findings indicate that age does have a relevant impact on postoperative QoL. Patient counseling should include age-related considerations, however, age itself cannot be regarded as a contraindication for oncoplastic surgery.


Asunto(s)
Neoplasias de la Mama , Mamoplastia , Anciano , Neoplasias de la Mama/cirugía , Femenino , Humanos , Mastectomía , Mastectomía Segmentaria , Persona de Mediana Edad , Medición de Resultados Informados por el Paciente , Calidad de Vida , Estudios Retrospectivos
18.
Cancer Chemother Pharmacol ; 87(2): 269-276, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33484280

RESUMEN

PURPOSE: We studied EGFR mutations in circulating tumor DNA (ctDNA) and explored their role in predicting the progression-free survival (PFS) of non-small cell lung cancer (NSCLC) patients treated with erlotinib or gefitinib. METHODS: The L858R, T790M mutations and exon 19 deletions were quantified in plasma using digital droplet polymerase chain reaction (ddPCR). The dynamics of ctDNA mutations over time and relationships with PFS were explored. RESULTS: In total, 249 plasma samples (1-13 per patient) were available from 68 NSCLC patients. The T790M and L858R or exon 19 deletion were found in the ctDNA of 49 and 56% patients, respectively. The median (range) concentration in these samples were 7.3 (5.1-3688.7), 11.7 (5.1-12,393.3) and 27.9 (5.9-2896.7) copies/mL, respectively. Using local polynomial regression, the number of copies of EGFR mutations per mL increased several months prior to progression on standard response evaluation. CONCLUSION: This change was more pronounced for the driver mutations than for the resistance mutations. In conclusion, quantification of EGFR mutations in plasma ctDNA was predictive of treatment outcomes in NSCLC patients. In particular, an increase in driver mutation copy number could predict disease progression.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/genética , ADN Tumoral Circulante/genética , Resistencia a Antineoplásicos/genética , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/genética , Clorhidrato de Erlotinib/administración & dosificación , Clorhidrato de Erlotinib/farmacología , Femenino , Gefitinib/administración & dosificación , Gefitinib/farmacología , Humanos , Neoplasias Pulmonares/genética , Masculino , Persona de Mediana Edad , Mutación , Supervivencia sin Progresión , Inhibidores de Proteínas Quinasas/farmacología , Resultado del Tratamiento
19.
Sci Rep ; 11(1): 2497, 2021 01 28.
Artículo en Inglés | MEDLINE | ID: mdl-33510227

RESUMEN

Endogenous immune mediated reactions of inflammation and angiogenesis are components of the spinal cord injury in patients with degenerative cervical myelopathy (DCM). The aim of this study was to identify alteration of certain mediators participating in angiogenetic and inflammatory reactions in patients with DCM. A consecutive series of 42 patients with DCM and indication for surgical decompression were enrolled for the study. 28 DCM patients were included, as CSF samples were taken preoperatively. We enrolled 42 patients requiring surgery for a thoracic abdominal aortic aneurysm (TAAA) as neurologically healthy controls. In 38 TAAA patients, CSF samples were taken prior to surgery and thus included. We evaluated the neurological status of patients and controls prior to surgery including NDI and mJOA. Protein-concentrations of factors with a crucial role in inflammation and angiogenesis were measured in CSF via ELISA testing (pg/ml): Angiopoietin 2, VEGF-A and C, RANTES, IL 1 beta and IL 8. Additionally, evaluated the status of the blood-spinal cord barrier (BSCB) by Reibers´diagnostic in all participants. Groups evidently differed in their neurological status (mJOA: DCM 10.1 ± 3.3, TAAA 17.3 ± 1.2, p < .001; NDI: DCM 47.4 ± 19.7, TAAA 5.3 ± 8.6, p < .001). There were no particular differences in age and gender distribution. However, we detected statistically significant differences in concentrations of mediators between the groups: Angiopoietin 2 (DCM 267.1.4 ± 81.9, TAAA 408.6 ± 177.1, p < .001) and VEGF C (DCM 152.2 ± 96.1, TAAA 222.4 ± 140.3, p = .04). DCM patients presented a mild to moderate BSCB disruption, controls had no signs of impairment. In patients with DCM, we measured decreased concentrations of angiogenic mediators. These results correspond to findings of immune mediated secondary harm in acute spinal cord injury. Reduced angiogenic activity could be a relevant part of the pathogenesis of DCM and secondary harm to the spinal cord.


Asunto(s)
Aneurisma de la Aorta Abdominal/sangre , Citocinas/sangre , Neovascularización Fisiológica , Traumatismos de la Médula Espinal/sangre , Anciano , Aneurisma de la Aorta Abdominal/cirugía , Femenino , Humanos , Inflamación/sangre , Inflamación/patología , Inflamación/cirugía , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Traumatismos de la Médula Espinal/patología , Traumatismos de la Médula Espinal/cirugía
20.
Rev. Fac. Odontol. (B.Aires) ; 36(82): 21-26, 2021. ilus
Artículo en Español | LILACS | ID: biblio-1290951

RESUMEN

El objetivo de este artículo es presentar una alternativa de tratamiento rehabilitador para pacientes jóvenes con gran pérdida de estructura dental vinculada a lesiones de origen no bacteriano. Se presenta el caso clínico de un paciente de 36 años de edad, con reflujo gastroesofágico crónico bajo tratamiento médico, que concurrió a la Cátedra de Odontología Integral Adultos de la Facultad de Odontología de la Universidad de Buenos Aires (FOUBA), en busca de un cambio estético en su sonrisa y relatando sensibilidad al calor, al frío y dolor al masticar. No manifestó sintomatología dolorosa a nivel muscular ni articular. En función de sus posibilidades económicas y de la etiología erosiva de las lesiones existentes en sus piezas dentarias, se llevó a cabo una rehabilitación oral adhesiva con resinas compuestas utilizando la sistematización de atención que sugiere la Cátedra. Las resinas compuestas actuales, en combinación con las técnicas y procedimientos desarrollados en este artículo han demostrado un adecuado comportamiento al ser utilizadas como restauraciones definitivas en pacientes que necesitan rehabilitación oral total debido a la gran pérdida de estructura dental por erosión ácida (AU)


Asunto(s)
Humanos , Masculino , Adulto , Erosión de los Dientes/terapia , Recubrimiento Dental Adhesivo , Resinas Compuestas/uso terapéutico , Argentina , Facultades de Odontología , Reflujo Gastroesofágico/complicaciones , Restauración Dental Permanente/métodos , Rehabilitación Bucal
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