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1.
J Orthop Trauma ; 38(8): e302-e306, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39007667

RESUMO

OBJECTIVES: The objective of this study was to report early outcomes of a novel screw-suture syndesmotic device compared with suture button fixation devices when treating traumatic syndesmotic instability. DESIGN: Retrospective chart review. SETTING: Single academic Level 1 Trauma Center. PATIENT SELECTION CRITERIA: All adult patients who had syndesmotic fixation with the novel device [novel syndesmotic repair implant (NSRI) group] compared with a suture button device (SB group) between January 2018 and December 2022. OUTCOME MEASURES AND COMPARISONS: Medial clear space and tibiofibular overlap measurements were compared immediately postoperatively and at the final follow-up. Patients were followed for a minimum of 1 year or skeletal healing. RESULTS: Fifty-nine patients (25 female) with an average age of 47 years (range 19-78 years) were in the NSRI group compared with 52 patients (20 female) with an average age of 41 years (range 18-73 years) in the SB group. There were no significant differences when comparing body mass index, diabetes, or smoking status between groups (P > 0.05). There was no difference when comparing the postoperative and final medial clear space measurements in the NSRI group compared with the SB group (P = 0.86; 95% confidence interval, -0.32 to 0.27). There was no difference when comparing the postoperative and final tibiofibular overlap measurements in the NSRI group compared with the SB group (P = 0.79; 95% confidence interval, -0.072 to 0.09). There were 3 cases of implant removal in the NSRI group compared with 2 in the SB group (P = 0.77). There was 1 failure in the NSRI group and none in the SB group. The remaining patients were all fully ambulatory at the final follow-up (P = 0.35). CONCLUSIONS: A novel screw-suture syndesmotic implant provides the fixation of a screw, and the flexibility of a suture had similar radiographic outcomes compared with suture button fixation devices in treating ankle syndesmotic instability. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.


Assuntos
Parafusos Ósseos , Instabilidade Articular , Humanos , Pessoa de Meia-Idade , Adulto , Feminino , Masculino , Estudos Retrospectivos , Idoso , Instabilidade Articular/cirurgia , Adulto Jovem , Traumatismos do Tornozelo/cirurgia , Fixação Interna de Fraturas/instrumentação , Fixação Interna de Fraturas/métodos , Resultado do Tratamento , Técnicas de Sutura/instrumentação , Adolescente
3.
Eur J Orthop Surg Traumatol ; 34(3): 1345-1348, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38133652

RESUMO

PURPOSE: Women with a history of pelvic fracture undergo cesarean section (CS) at a higher rate than the general population. The purpose of our study is to query obstetricians on their preferences. METHODS: An electronic survey consisting of 22 radiographs of patients who underwent pelvic fixation was sent to obstetricians at 3 academic medical centers. For each radiograph, a hypothetical scenario was given, and the respondents were asked if they would elect for a vaginal delivery or CS. RESULTS: We collected 58 responses. The overall CS rate was 59%. Respondents were significantly more likely to elect for CS with trans-symphyseal fixation or sacroiliac fixation, independently (p < 0.001). DISCUSSION: Obstetricians are likely to elect for elective CS in the presence of pelvic implants especially in patients with trans-symphyseal and sacroiliac fixation. Based on there is an opportunity for collaboration between orthopedic trauma surgeons and obstetricians.


Assuntos
Cesárea , Ossos Pélvicos , Humanos , Feminino , Gravidez , Cesárea/efeitos adversos , Obstetra , Inquéritos e Questionários , Pelve/diagnóstico por imagem , Pelve/cirurgia , Ossos Pélvicos/diagnóstico por imagem , Ossos Pélvicos/cirurgia , Ossos Pélvicos/lesões
4.
Sci Rep ; 13(1): 13769, 2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37612341

RESUMO

New measurements from the Arctic ± 40 days around the summer solstice show reflected sunlight from north of 80°N decreases 20-35%. Arctic sea ice coverage decreases 7-9% over this same time period (as reported by the NSIDC) implying Arctic sea ice albedo decreases in addition to the sea ice receding. Similar Antarctic measurements provide a baseline to which Arctic measurements are compared. The Antarctic reflected sunlight south of 80°S is up to 30% larger than the Arctic reflectance and is symmetric around the solstice implying constant Antarctic reflectivity. Arctic reflected sunlight 20 days after solstice is > 100W/m2 less than Antarctic reflected sunlight. For perspective, this is enough heat to melt > 1 mm/hour of ice. This finding should be compared with climate models and in reanalysis data sets to further quantify sea ice albedo's role in Arctic Amplification. The measurements were made with previously unpublished pixelated radiometers on Global Positioning System satellites from 2014 to 2019. The GPS orbits give each radiometer instantaneous and continuous views of 37% of the Earth, two daily full views of the Arctic and Antarctic. Furthermore, the GPS constellation gives full-time full-Earth coverage that may provide data that complements existing limited field of view instruments that provide a less synoptic Earth view.

5.
Artigo em Inglês | MEDLINE | ID: mdl-37053039

RESUMO

INTRODUCTION: In 1963, the American Academy of Orthopaedic Surgeons administered the Orthopaedic In-Training Examination (OITE), the first and longest running yearly medical specialty examination. There have been no recent studies to evaluate the content of the musculoskeletal trauma section of the OITE. METHODS: We analyzed all questions that were classified by the American Academy of Orthopaedic Surgeons as musculoskeletal trauma from 2012 to 2019. We recorded the number of musculoskeletal trauma questions in each examination, the topics and imaging modalities tested, the references cited, and the taxonomy classification of each question. We extrapolated from a similar musculoskeletal trauma study published in 2011 to create the previous examination cohort for comparison. RESULTS: For the current cohort, the average number of musculoskeletal trauma questions was 43.5 questions per examination (18.4%). The most frequently tested topics were proximal tibia fractures, pediatric trauma, hip fractures, and diaphyseal femur fractures, respectively. In previous examinations, questions from T1 and 2 were tested significantly more frequently compared with the current examinations (P < 0.001 and P = 0.02, respectively). In the current cohort, T3 questions were tested significantly more frequently than previous examinations (P = 0.001). Previous examinations had significantly more questions without an image (36 questions per year versus 25 questions per year, P < 0.001). In current versions of the examination, radiographs are tested significantly more frequently than other imaging modalities (P < 0.001). DISCUSSION: The musculoskeletal trauma section of the OITE has evolved. To improve and focus study efforts, residents may use this study as a guide when preparing for the examination.


Assuntos
Fraturas Ósseas , Internato e Residência , Ortopedia , Humanos , Estados Unidos , Criança , Educação de Pós-Graduação em Medicina/métodos , Ortopedia/educação , Avaliação Educacional
8.
JBJS Case Connect ; 11(4)2021 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-34807888

RESUMO

CASE: A 14-year-old boy sustained 22 cm of femur bone loss after a motor vehicle accident. The patient underwent treatment with the membrane-inducing "Masquelet" technique for management of the injury. The grafts incorporated to form new bone and fill-in the void. CONCLUSION: Although the Masquelet technique is thoroughly described in adult orthopaedic trauma and oncology literature, there are minimal reports to support its use in pediatric patients. Five-year follow-up data on this patient concluded that utilization of this technique for significant bone defects proves to be a safe and effective alternative for the management of pediatric trauma patients.


Assuntos
Osso e Ossos , Fêmur , Adolescente , Adulto , Criança , Fêmur/cirurgia , Humanos , Masculino
9.
J Psychosom Res ; 150: 110634, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34610494

RESUMO

OBJECTIVE: Severe hypoglycemia complicates insulin therapy for type 1 diabetes, with impaired awareness of hypoglycemia (IAH) being a major risk factor. We explored associations between the personality traits, alexithymia and perfectionism, and cognitive barriers to hypoglycemia avoidance described in IAH, and evaluated their prevalence in people with and without IAH. METHODS: Cross-sectional exploratory study. Ninety adults with type 1 diabetes, 54 hypoglycemia aware and 36 with IAH, completed validated questionnaires exploring alexithymia (Total Alexithymia Scale [TAS-20]) and perfectionism (Frost Multidimensional Perfectionism Scale [FMPS]); and cognitive barriers related to hypoglycemia avoidance (Attitudes to Awareness Questionnaire [A2A]. RESULTS: Alexithymia and perfectionism scores correlated positively with cognitive barriers associated with IAH. Specifically, alexthymia scores correlated with the 'Hyperglycaemia Avoidance Prioritised' factor (r = 0.265; p = .02, n = 77) and the 'Asymptomatic Hypoglycemia Normalised' factor (r = 0.252-0.255; p = .03, n = 77). Perfectionism scores correlated with the 'Hyperglycaemia Avoidance Prioritised' factor (r = 0.525; p < .001, n = 66). Overall, IAH participants were significantly more likely to score at the high end for alexithymia (17.6% vs. 1.9%, p = .008, n = 87) and at the extreme ends (high and low) for perfectionism (69.0% vs. 40.0%, χ2 (1) = 6.24, p = .01, n = 77). CONCLUSION: These novel data showing associations between alexithymia and perfectionism scores and maladaptive health beliefs in IAH suggest the intriguing possibility that personality traits may contribute to the risk of IAH, perhaps through their influence on incentives to avoid hypoglycemia. If confirmed, measuring such traits may help tailor early adjunctive psychological intervention to reduce hypoglycemia burden for people with IAH.


Assuntos
Diabetes Mellitus Tipo 1 , Hipoglicemia , Perfeccionismo , Adulto , Sintomas Afetivos/epidemiologia , Conscientização , Estudos Transversais , Diabetes Mellitus Tipo 1/complicações , Humanos
10.
JBJS Case Connect ; 11(3)2021 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-34237044

RESUMO

CASE: We present a series of 3 pelvic ring injuries that occurred on 1 high-speed water slide at a theme park in Orlando, FL. This is the first time this injury has been reported at a water park in the United States. All patients underwent surgical management and had an excellent outcome. CONCLUSION: Pelvic ring injuries usually occur because of high-energy mechanisms, but unique mechanisms of injuries are possible. We aim to draw attention to this unique mechanism of injury because serious injury may occur to riders. Water parks should use the information presented in this study to develop and refine safety requirements for patrons.


Assuntos
Fraturas Ósseas , Água , Fraturas Ósseas/etiologia , Fraturas Ósseas/cirurgia , Humanos
11.
Clin Child Psychol Psychiatry ; 26(3): 682-694, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33624515

RESUMO

This article examines the combined roles of attachment mentalisation and diabetes distress in the psychological development of young people with Type 1 diabetes (T1D). We use these ideas to unify the evidence for psychological variables affecting young people and their families and suggest how diabetes distress and mentalisation might be part of the pathways for development of psychiatric diagnoses.Attachment theory's central hypothesis is that a secure relationship with a care-giver in the early life of a child is essential to normal emotional and relational development, whilst diabetes distress is a well recognised phenomena of burden experienced by both child and parent in relation to the condition.We extend the ideas of attachment, into the psychological adaptation processes for young people at the time of diagnosis of T1D with emphasis on the function of the parent/caregiver in mentalising the experience of the child. We also connect our current understanding of diabetes distress to the associated increased risk for disorders of eating and personality in T1D.Using principles learnt in other areas of psychotherapeutic practice we end by suggesting interventions that could impact mental health and diabetes outcomes using the mentalisation model.


Assuntos
Diabetes Mellitus Tipo 1 , Transtornos Mentais , Mentalização , Adolescente , Criança , Emoções , Humanos , Saúde Mental , Apego ao Objeto
12.
Diabet Med ; 38(7): e14505, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33368581

RESUMO

BACKGROUND: Despite its poor prognosis, the psychological factors associated with recurrent diabetic ketoacidosis are poorly understood. In people with type 1 diabetes, we assessed for psychopathology in those with and without recurrent diabetic ketoacidosis (DKA). METHOD: The design was a case-control study. Cases were defined as people with two or more DKA episodes in a 12-month period (recurrent DKA). Cases and controls were matched for gender and age. We compared groups for scores on Beck's Anxiety Inventory (BAI), Beck's Depression Inventory II, Difficulty in Emotion Regulation Scale (DERS), Experiences in Close Relationships-Revised, Standardised Assessment of Personality-Abbreviated Scale (SAPAS), Interpersonal Problem Inventory, Eating Disorder Examination Questionnaire and Problem Areas in Diabetes (PAID) using unpaired t-tests or Mann-Whitney U tests for parametric and non-parametric data, respectively. Correction was made for multiple testing. RESULTS: In all, 23 cases and 23 controls were recruited with mean age 31.0 (11.4) years and 65.2% were men. Cases had higher HbA1c levels than controls (101.1 (23.2) vs. 85.7 (21.7) mmol/mol, (p = 0.02)). Compared to controls, people with recurrent DKA had higher scores on the BAI (p = 0.004), PAID (p = 0.004), DERS (p = 0.001) and SAPAS (p < 0.001). Sixteen of 23 (69.6%) cases screened positive for a personality disorder compared to 6 of 23 (26.1%) controls. CONCLUSIONS: People with recurrent DKA have elevated levels of anxiety and diabetes distress, greater difficulty with emotion regulation and personality dysfunction compared to matched controls.


Assuntos
Cetoacidose Diabética/psicologia , Adulto , Ansiedade/diagnóstico , Estudos de Casos e Controles , Depressão/diagnóstico , Regulação Emocional , Feminino , Hemoglobinas Glicadas/análise , Humanos , Masculino , Transtornos da Personalidade/diagnóstico , Angústia Psicológica , Recidiva
13.
Hear Res ; 390: 107949, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32200300

RESUMO

Phantom electrode (PE) stimulation can extend the lower limit of pitch perception with cochlear implants (CIs) by using simultaneous out-of-phase stimulation of the most apical primary electrode and the adjacent basal compensating electrode. The total electrical field may push the excitation pattern beyond the most apical electrode to elicit a lower pitch, depending on the ratio of current between the compensating and primary electrodes (i.e., the compensation coefficient σ). This study tested the hypothesis that dynamic current steering of PE stimuli can be implemented by varying σ over time to encode spectral details in low frequencies. To determine the range of σ for current steering and the corresponding current levels, Experiment 1 tested CI users' loudness balance and pitch ranking of static PE stimuli with σ from 0 to 0.6 in steps of 0.2. It was found that the equal-loudness most comfortable level significantly increased with σ and can be modeled by a piecewise linear function of σ. Consistent with the previous findings, higher σ elicited either lower or similar pitches without salient pitch reversals than lower σ. Based on the results of Experiment 1, Experiment 2 created flat, rising, and falling pitch contours of 300-1000 ms using dynamic PE stimuli with time-varying σ from 0 to 0.6 and equal-loudness current levels. In a pitch contour identification (PCI) task, CI users scored 80% and above on average. Increasing the stimulus duration from 300 to 1000 ms slightly but did not significantly improve the PCI scores. Across subjects, the 1000-ms PCI scores in Experiment 2 were significantly correlated with the cumulative pitch-ranking sensitivity in Experiment 1. It is thus feasible to use dynamic current steering with PE to encode low-frequency pitch cues for CI users.


Assuntos
Implante Coclear/instrumentação , Implantes Cocleares , Sinais (Psicologia) , Surdez/reabilitação , Pessoas com Deficiência Auditiva/reabilitação , Percepção da Altura Sonora , Estimulação Acústica , Adulto , Idoso , Surdez/diagnóstico , Surdez/fisiopatologia , Surdez/psicologia , Estimulação Elétrica , Feminino , Audição , Humanos , Percepção Sonora , Masculino , Pessoa de Meia-Idade , Pessoas com Deficiência Auditiva/psicologia , Discriminação da Altura Tonal
15.
J Glob Oncol ; 4: 1-10, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-30084749

RESUMO

Purpose Epidemiologic data from several populations suggest that metformin may decrease cancer risk and mortality in patients with colorectal cancer (CRC) and type II diabetes mellitus (DM). Although type II DM and CRC are major health problems in the Middle East, no investigations have been performed to test the effect metformin has on the outcome of patients with type II DM and CRC who are also treated with metformin. Materials and Methods We retrospectively reviewed the medical records of 1,902 patients diagnosed with CRC at King Hussein Cancer Center between January 2004 and December 2012, and identified 349 patients (18%) with type II DM; we censored the data of 28 patients because their antidiabetic medications were unknown. We then categorized these 321 patients into two groups: 192 patients treated with metformin (group A) and 129 patients treated with other antidiabetic medications (group B). Results Group A patients had significantly longer overall survival (89 months; 95% CI, 66 to 112 months) and progression-free survival (47 months; 95% CI, 15 to 79 months) than group B patients (overall survival: 36 months; 95% CI, 24 to 48 months; P ≤ .001; progression-free survival: 21 months; 95% CI, 13 to 29 months; P = .016). After adjustment for age, sex, body mass index, aspirin use, anticholesterol treatment, and CRC stage, group A patients had a 40% reduction in mortality (hazard ratio, 0.58; 95% CI, 0.4% to 0.85%; P = .005). Conclusion Our results support findings from other populations that patients with diabetes and CRC who are also treated with metformin have better outcomes than those treated with other antidiabetic medications.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Diabetes Mellitus Tipo 2/mortalidade , Diabetes Mellitus Tipo 2/patologia , Feminino , Humanos , Hipoglicemiantes/farmacologia , Masculino , Metformina/farmacologia , Pessoa de Meia-Idade , Oriente Médio , Reprodutibilidade dos Testes , Estudos Retrospectivos , Análise de Sobrevida
16.
Diabetes Technol Ther ; 18(9): 551-4, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27479198

RESUMO

BACKGROUND: To find out whether children with type 1 diabetes accept a humanoid robot as an assistant in their diabetes management. In particular, the study aims to determine how the patients feel the robot may contribute to their care and how they respond to advice and education provided by the robot. SUBJECTS AND METHODS: A humanoid robot was used in clinic and its acceptability was tested over 3 months in 37 children (aged 6-16 years) with type 1 diabetes during their clinic visits. RESULTS: The obtained result showed that the overall patients' acceptability is 86.7%. However, the level of acceptability varies depending on the age group; patients aged 6-9 years showed the highest acceptability level of 94.8%, while the older age groups, 10-12 and 13-16 years, showed lower acceptability levels of 85.0% and 83.0%, respectively. There was no difference in the overall acceptability of the robot between the male and female patients (87.0% and 86.5%, respectively). Furthermore, features of the robot that were highly desirable include ability of the robot to give advice on high/low blood glucose (BG) levels (92.0%), how much the patients like the robot (91.4%), and ability of the robot to give advice on BG patterns (90.6%). In contrast, some other features were found least acceptable such as how likely patients want the robot as a companion (81.0%) and calculation of insulin doses with meals (82.53%). Analysis of variance across the responses of different age groups showed that P-value = 0.00003. CONCLUSION: Use of robots as a new device to support diabetes self-management in children was well accepted by patients.


Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 1/terapia , Aceitação pelo Paciente de Cuidados de Saúde , Robótica , Autocuidado , Adolescente , Criança , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Masculino
17.
Prim Care Diabetes ; 10(5): 376-82, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27006306

RESUMO

AIM: Evidence for the efficacy of psychological skills training as a method of supporting patients' self-management is growing, but there is a shortage of mental health providers with specialist diabetes knowledge to deliver them. Primary care nurses are now increasingly expected to learn and use these techniques. This study explores nurse experience of training in six psychological skills to support patients' self-management of type 2 diabetes. METHODS: Semi-structured interviews elicited themes relating to nurses' experiences of participating in a trial of a psychological intervention, the Diabetes-6 study (D-6). Nurses were employed in GP surgeries in 5 South London boroughs. Thematic framework analysis was used to compare and contrast themes across participants. Nine nurses delivering the intervention (n=11), and 7 from the control intervention (n=12, no psychological element) were interviewed. RESULTS: Three key themes were identified: (i) positive and negative impact of D6 on nurses' practice: positives included patient empowerment; negatives included patients' capacity to engage; (ii) professional boundaries including concerns about over-stepping role as a nurse and (iii) concerns about degree of support from physicians at participating practices in integrating psychological and diabetes care. CONCLUSION: Primary care nurses report that psychological skills training can have a positive impact on patient care. Significant role adjustment is required, which may be aided by additional support from the practice team. Qualitative evaluation of effectiveness of psychological interventions may reveal processes that hinder or contribute to efficacy and translation. Appropriate support is necessary for primary care nurses to deliver psychological therapies with confidence.


Assuntos
Diabetes Mellitus Tipo 2/enfermagem , Educação Continuada em Enfermagem , Capacitação em Serviço , Entrevista Motivacional , Papel do Profissional de Enfermagem , Enfermagem de Atenção Primária , Autocuidado , Agendamento de Consultas , Atitude do Pessoal de Saúde , Terapia Cognitivo-Comportamental , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Entrevistas como Assunto , Londres , Pessoa de Meia-Idade , Relações Enfermeiro-Paciente , Educação de Pacientes como Assunto , Participação do Paciente , Pesquisa Qualitativa
18.
PLoS One ; 10(8): e0135447, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26270534

RESUMO

Mycobacterium tuberculosis harbors over 160 genes encoding PE/PPE proteins, several of which have roles in the pathogen's virulence. A number of PE/PPE proteins are secreted via Type VII secretion systems known as the ESX secretion systems. One PE protein, LipY, has a triglyceride lipase domain in addition to its PE domain. LipY can regulate intracellular triglyceride levels and is also exported to the cell wall by one of the ESX family members, ESX-5. Upon export, LipY's PE domain is removed by proteolytic cleavage. Studies using cells and crude extracts suggest that LipY's PE domain not only directs its secretion by ESX-5, but also functions to inhibit its enzymatic activity. Here, we attempt to further elucidate the role of LipY's PE domain in the regulation of its enzymatic activity. First, we established an improved purification method for several LipY variants using detergent micelles. We then used enzymatic assays to confirm that the PE domain down-regulates LipY activity. The PE domain must be attached to LipY in order to effectively inhibit it. Finally, we determined that full length LipY and the mature lipase lacking the PE domain (LipYΔPE) have similar melting temperatures. Based on our improved purification strategy and activity-based approach, we concluded that LipY's PE domain down-regulates its enzymatic activity but does not impact the thermal stability of the enzyme.


Assuntos
Proteínas de Bactérias/química , Hidrolases de Éster Carboxílico/química , Mycobacterium tuberculosis/enzimologia , Fatores de Virulência/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/isolamento & purificação , Proteínas de Bactérias/metabolismo , Sistemas de Secreção Bacterianos/química , Sistemas de Secreção Bacterianos/genética , Sistemas de Secreção Bacterianos/metabolismo , Hidrolases de Éster Carboxílico/genética , Hidrolases de Éster Carboxílico/isolamento & purificação , Hidrolases de Éster Carboxílico/metabolismo , Estabilidade Enzimática , Mycobacterium tuberculosis/genética , Estrutura Terciária de Proteína , Triglicerídeos/genética , Triglicerídeos/metabolismo , Fatores de Virulência/genética , Fatores de Virulência/isolamento & purificação , Fatores de Virulência/metabolismo
19.
Oncotarget ; 6(30): 28929-37, 2015 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-26078337

RESUMO

There is an unmet clinical need for molecularly directed therapies available for metastatic colorectal cancer. Comprehensive genomic profiling has the potential to identify actionable genomic alterations in colorectal cancer. Through comprehensive genomic profiling we prospectively identified 6 RET fusion kinases, including two novel fusions of CCDC6-RET and NCOA4-RET, in metastatic colorectal cancer (CRC) patients. RET fusion kinases represent a novel class of oncogenic driver in CRC and occurred at a 0.2% frequency without concurrent driver mutations, including KRAS, NRAS, BRAF, PIK3CA or other fusion tyrosine kinases. Multiple RET kinase inhibitors were cytotoxic to RET fusion kinase positive cancer cells and not RET fusion kinase negative CRC cells. The presence of a RET fusion kinase may identify a subset of metastatic CRC patients with a high response rate to RET kinase inhibition. This is the first characterization of RET fusions in CRC patients and highlights the therapeutic significance of prospective comprehensive genomic profiling in advanced CRC.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Fusão Gênica , Proteínas Proto-Oncogênicas c-ret/genética , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/antagonistas & inibidores , Biomarcadores Tumorais/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/patologia , Proteínas do Citoesqueleto/genética , Bases de Dados Genéticas , Relação Dose-Resposta a Droga , Feminino , Perfilação da Expressão Gênica/métodos , Predisposição Genética para Doença , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Coativadores de Receptor Nuclear/genética , Fenótipo , Estudos Prospectivos , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-ret/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-ret/metabolismo , Fatores de Tempo , Resultado do Tratamento
20.
Anticancer Res ; 35(3): 1567-73, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25750312

RESUMO

AIM: To evaluate feasible doses of weekly everolimus and irinotecan given with cetuximab for previously treated metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Adults with mCRC that progressed after 5-fluorouracil or capecitabine-plus-oxaliplatin were treated using a sequential dose escalation scheme. Dosing decisions were based on the probability of experiencing a dose-limiting toxicity (DLT) during the first two 21-day treatment cycles. RESULTS: Patients received everolimus 30 mg/week plus irinotecan 350 mg/m2 q3w (n=5; dose A1) or everolimus 30 mg/week plus irinotecan 250 mg/m2 q3w (n=14; dose B1). Among patients evaluable for the maximum tolerated dose, two out of four in A1 and one out of eight in B1 experienced four DLTs. The trial was terminated early based on changes in clinical practice and emerging data on everolimus dosing. CONCLUSION: The feasible doses of everolimus and irinotecan administered with cetuximab as second-line therapy in mCRC were 30 mg/week and 250 mg/m2, respectively.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Cetuximab , Neoplasias Colorretais/patologia , Everolimo , Feminino , Humanos , Irinotecano , Masculino , Pessoa de Meia-Idade , Mutação , Metástase Neoplásica , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas p21(ras) , Sirolimo/administração & dosagem , Sirolimo/análogos & derivados , Proteínas ras/genética
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