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1.
Eur J Orthop Surg Traumatol ; 34(3): 1345-1348, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38133652

RESUMEN

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.


Asunto(s)
Cesárea , Huesos Pélvicos , Humanos , Femenino , Embarazo , Cesárea/efectos adversos , Obstetras , Encuestas y Cuestionarios , Pelvis/diagnóstico por imagen , Pelvis/cirugía , Huesos Pélvicos/diagnóstico por imagen , Huesos Pélvicos/cirugía , Huesos Pélvicos/lesiones
2.
Diabet Med ; 38(7): e14505, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33368581

RESUMEN

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.


Asunto(s)
Cetoacidosis Diabética/psicología , Adulto , Ansiedad/diagnóstico , Estudios de Casos y Controles , Depresión/diagnóstico , Regulación Emocional , Femenino , Hemoglobina Glucada/análisis , Humanos , Masculino , Trastornos de la Personalidad/diagnóstico , Distrés Psicológico , Recurrencia
6.
J Orthop Trauma ; 38(8): e302-e306, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39007667

RESUMEN

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.


Asunto(s)
Tornillos Óseos , Inestabilidad de la Articulación , Humanos , Persona de Mediana Edad , Adulto , Femenino , Masculino , Estudios Retrospectivos , Anciano , Inestabilidad de la Articulación/cirugía , Adulto Joven , Traumatismos del Tobillo/cirugía , Fijación Interna de Fracturas/instrumentación , Fijación Interna de Fracturas/métodos , Resultado del Tratamiento , Técnicas de Sutura/instrumentación , Adolescente
7.
J Bacteriol ; 195(4): 886-95, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23243304

RESUMEN

Kingella kingae is an emerging bacterial pathogen that is being recognized increasingly as an important etiology of septic arthritis, osteomyelitis, and bacteremia, especially in young children. The pathogenesis of K. kingae disease begins with bacterial adherence to respiratory epithelium, which is dependent on type IV pili and is influenced by two PilC-like proteins called PilC1 and PilC2. Production of either PilC1 or PilC2 is necessary for K. kingae piliation and bacterial adherence. In this study, we set out to further investigate the role of PilC1 and PilC2 in type IV pilus-associated phenotypes. We found that PilC1 contains a functional 9-amino-acid calcium-binding (Ca-binding) site with homology to the Pseudomonas aeruginosa PilY1 Ca-binding site and that PilC2 contains a functional 12-amino-acid Ca-binding site with homology to the human calmodulin Ca-binding site. Using targeted mutagenesis to disrupt the Ca-binding sites, we demonstrated that the PilC1 and PilC2 Ca-binding sites are dispensable for piliation. Interestingly, we showed that the PilC1 site is necessary for twitching motility and adherence to Chang epithelial cells, while the PilC2 site has only a minor influence on twitching motility and no influence on adherence. These findings establish key differences in PilC1 and PilC2 function in K. kingae and provide insights into the biology of the PilC-like family of proteins.


Asunto(s)
Adhesión Bacteriana/fisiología , Calcio/metabolismo , Proteínas Fimbrias/metabolismo , Fimbrias Bacterianas/fisiología , Kingella kingae/metabolismo , Sitios de Unión , Proteínas Fimbrias/genética , Fimbrias Bacterianas/clasificación , Regulación Bacteriana de la Expresión Génica/fisiología , Kingella kingae/genética , Movimiento , Fenotipo , Plásmidos , Unión Proteica
8.
Infect Immun ; 81(11): 4280-9, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24002068

RESUMEN

Neisseria gonorrhoeae PilC1 is a member of the PilC family of type IV pilus-associated adhesins found in Neisseria species and other type IV pilus-producing genera. Previously, a calcium-binding domain was described in the C-terminal domains of PilY1 of Pseudomonas aeruginosa and in PilC1 and PilC2 of Kingella kingae. Genetic analysis of N. gonorrhoeae revealed a similar calcium-binding motif in PilC1. To evaluate the potential significance of this calcium-binding region in N. gonorrhoeae, we produced recombinant full-length PilC1 and a PilC1 C-terminal domain fragment. We show that, while alterations of the calcium-binding motif disrupted the ability of PilC1 to bind calcium, they did not grossly affect the secondary structure of the protein. Furthermore, we demonstrate that both full-length wild-type PilC1 and full-length calcium-binding-deficient PilC1 inhibited gonococcal adherence to cultured human cervical epithelial cells, unlike the truncated PilC1 C-terminal domain. Similar to PilC1 in K. kingae, but in contrast to the calcium-binding mutant of P. aeruginosa PilY1, an equivalent mutation in N. gonorrhoeae PilC1 produced normal amounts of pili. However, the N. gonorrhoeae PilC1 calcium-binding mutant still had partial defects in gonococcal adhesion to ME180 cells and genetic transformation, which are both essential virulence factors in this human pathogen. Thus, we conclude that calcium binding to PilC1 plays a critical role in pilus function in N. gonorrhoeae.


Asunto(s)
Adhesinas Bacterianas/metabolismo , Adhesión Bacteriana , Proteínas Fimbrias/metabolismo , Fimbrias Bacterianas/fisiología , Neisseria gonorrhoeae/fisiología , Adhesinas Bacterianas/genética , Sitios de Unión , Calcio/metabolismo , Línea Celular , Análisis Mutacional de ADN , Células Epiteliales/microbiología , Proteínas Fimbrias/genética , Fimbrias Bacterianas/genética , Humanos , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Neisseria gonorrhoeae/genética , Conformación Proteica , Estructura Terciaria de Proteína
9.
Cancer ; 119(24): 4223-30, 2013 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-24105075

RESUMEN

BACKGROUND: Irinotecan is cytotoxic in patients with advanced colorectal cancer (CRC). SN-38 (10-hydroxy-7-ethyl-camptothecin) is the active metabolite of irinotecan. Attachment of polyethylene glycol (PEG) polymer chains (pegylation) to SN-38 (EZN-2208) increases the solubility, exposure, and half-life of SN-38. Preclinical studies demonstrated superior in vitro efficacy of EZN-2208 when it was tested in irinotecan-refractory human CRC cell lines. METHODS: Patients with metastatic or locally recurrent CRC who had previously received 5-flurouracil (5-FU), oxaliplatin, and irinotecan were assigned to receive EZN-2208 monotherapy (9 mg/m(2) on days 1, 8, and 15 every 28 days for patients with KRAS-mutant tumors only [arm A]), and patients with KRAS wild-type tumors were randomized (2:1) to receive either EZN-2208 plus cetuximab (400 mg/m(2) loading dose on day 1 followed by 250 mg/m(2) weekly starting on day 8 [arm B]) or irinotecan 125 mg/m(2) on days 1 and 8 every 21 days plus cetuximab at the same doses indicated above (arm C). RESULTS: The overall response rate and progression-free survival were 0% and 1.8 months, respectively, in arm A; 10.7% and 4.9 months (95% confidence interval [CI], 3.2-5.8 months), respectively, in arm B; and 14.3% and 3.7 months (95% CI, 2.1-5.8 months), respectively, in arm C. EZN-2208 was well tolerated in combination with cetuximab. No statistically significant difference in survival was observed between arm B (9.8 months; 95% CI, 7.2-11.2 months) and arm C (9.1 months; 95% CI, 6.0-13.0 months). CONCLUSIONS: EZN-2208, either as monotherapy or in combination with cetuximab, was well tolerated in patients with refractory CRC. Overall survival and progression-free survival were similar in the cetuximab plus irinotecan arm and the EZN-2208 arm.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Camptotecina/análogos & derivados , Neoplasias Colorrectales/tratamiento farmacológico , Polietilenglicoles/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/administración & dosificación , Antineoplásicos Fitogénicos/administración & dosificación , Camptotecina/administración & dosificación , Camptotecina/uso terapéutico , Línea Celular Tumoral , Cetuximab , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Supervivencia sin Enfermedad , Femenino , Genes ras , Humanos , Irinotecán , Masculino , Persona de Mediana Edad , Mutación , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/genética , Polietilenglicoles/administración & dosificación , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas p21(ras) , Adulto Joven , Proteínas ras/genética
10.
Ann Surg ; 258(6): 879-86, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23657083

RESUMEN

OBJECTIVE: To determine whether 1 of 2 vaccines based on dendritic cells (DCs) and poxvectors encoding CEA (carcinoembryonic antigen) and MUC1 (PANVAC) would lengthen survival in patients with resected metastases of colorectal cancer (CRC). BACKGROUND: Recurrences after complete resections of metastatic CRC remain frequent. Immune responses to CRC are associated with fewer recurrences, suggesting a role for cancer vaccines as adjuvant therapy. Both DCs and poxvectors are potent stimulators of immune responses against cancer antigens. METHODS: Patients, disease-free after CRC metastasectomy and perioperative chemotherapy (n = 74), were randomized to injections of autologous DCs modified with PANVAC (DC/PANVAC) or PANVAC with per injection GM-CSF (granulocyte-macrophage colony-stimulating factor). Endpoints were recurrence-free survival overall survival, and rate of CEA-specific immune responses. Clinical outcome was compared with that of an unvaccinated, contemporary group of patients who had undergone CRC metastasectomy, received similar perioperative therapy, and would have otherwise been eligible for the study. RESULTS: Recurrence-free survival at 2 years was similar (47% and 55% for DC/PANVAC and PANVAC/GM-CSF, respectively) (χ P = 0.48). At a median follow-up of 35.7 months, there were 2 of 37 deaths in the DC/PANVAC arm and 5 of 37 deaths in the PANVAC/GM-CSF arm. The rate and magnitude of T-cell responses against CEA was statistically similar between study arms. As a group, vaccinated patients had superior survival compared with the contemporary unvaccinated group. CONCLUSIONS: Both DC and poxvector vaccines have similar activity. Survival was longer for vaccinated patients than for a contemporary unvaccinated group, suggesting that a randomized trial of poxvector vaccinations compared with standard follow-up after metastasectomy is warranted. (NCT00103142).


Asunto(s)
Vacunas contra el Cáncer , Antígeno Carcinoembrionario , Neoplasias Colorrectales/prevención & control , Células Dendríticas , Factor Estimulante de Colonias de Granulocitos y Macrófagos , Inmunización/métodos , Glicoproteínas de Membrana , Mucina-1 , Recurrencia Local de Neoplasia/prevención & control , Adulto , Anciano , Antígeno Carcinoembrionario/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mucina-1/genética , Metástasis de la Neoplasia , Poxviridae/genética
11.
Sci Rep ; 13(1): 13769, 2023 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-37612341

RESUMEN

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.

12.
Artículo en Inglés | MEDLINE | ID: mdl-37053039

RESUMEN

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.


Asunto(s)
Fracturas Óseas , Internado y Residencia , Ortopedia , Humanos , Estados Unidos , Niño , Educación de Postgrado en Medicina/métodos , Ortopedia/educación , Evaluación Educacional
13.
Ann Surg ; 256(4): 642-50, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22968062

RESUMEN

OBJECTIVE: We hypothesized that metachronous colorectal liver metastases (CLM) have different biology after failure of oxaliplatin (FOLFOX) compared to 5-fluorouracil (5-FU) or no chemotherapy for adjuvant treatment of colorectal cancer (CRC). BACKGROUND: It is unclear whether patients treated with liver resection for metachronous CLM after adjuvant FOLFOX for CRC have worse outcomes than those who received 5-FU or no chemotherapy. METHODS: We identified 341 patients who underwent hepatectomy for metachronous CLM (disease-free interval ≥12 months, 1993-2010). Mass-spectroscopy genotyping for somatic gene mutations in CLM was performed in a subset of 129 patients. RESULTS: Adjuvant treatment for primary CRC was FOLFOX in 77 patients, 5-FU in 169 patients, and no chemotherapy in 95 patients. Node-positive primary was comparable between FOLFOX and 5-FU but lower in the no-chemotherapy group (P < 0.0001). Median metastasis size was smaller in the FOLFOX group (2.5 cm) than in the 5-FU (3.0 cm) or no-chemotherapy (3.5 cm) groups, (P = 0.008) although prehepatectomy chemotherapy utilization, metastases number, and carcinoembryonic antigen levels were similar. Disease-free survival (DFS) and overall survival (OS) rates after hepatectomy were worse in patients treated with adjuvant FOLFOX [DFS at 3 years: 14% vs 38% (5-FU) vs 45% (no-chemo), OS at 3 years: 58% vs 70% (5-FU) vs 84% (no-chemo)]. On multivariate analysis, adjuvant FOLFOX was associated with worse DFS (P < 0.0001) and OS (P < 0.0001). Mutation analysis revealed ≥1 mutations in 57% of patients (27/47) after FOLFOX, 29% (12/41) after 5-FU, and 32% (13/41) after no chemotherapy (P = 0.011). CONCLUSIONS: Adjuvant FOLFOX for primary CRC is associated with a high rate of somatic mutations in liver metastases and inferior outcomes after hepatectomy for metachronous CLM.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Hepatectomía , Neoplasias Hepáticas/secundario , Anciano , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/uso terapéutico , Biomarcadores de Tumor/genética , Quimioterapia Adyuvante , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Análisis Mutacional de ADN , Femenino , Fluorouracilo/uso terapéutico , Estudios de Seguimiento , Humanos , Leucovorina/uso terapéutico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/cirugía , Masculino , Espectrometría de Masas , Persona de Mediana Edad , Análisis Multivariante , Mutación , Compuestos Organoplatinos/uso terapéutico , Complicaciones Posoperatorias , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento
14.
Int J Cancer ; 129(8): 1963-9, 2011 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-21154746

RESUMEN

Soft tissue sarcomas (STS) represent a diverse group of histologic subtypes with targetable molecular alterations, often treated as a single disease. Sunitinib malate is a multitargeted receptor tyrosine kinase inhibitor active in other solid tumors carrying similar alterations (i.e., imatinib mesylate-refractory gastrointestinal stromal tumors). This single-institution phase II study investigated the safety and efficacy of sunitinib malate in three common STS subtypes. Patients with documented unresectable or metastatic STS (liposarcoma, leiomyosarcoma and malignant fibrous histiocytoma [MFH]), measurable disease, and 3 or less prior lines of therapy were eligible. Treatment consisted of sunitinib malate, 50 mg daily, for 4 weeks every 6 weeks. Forty-eight patients were enrolled, and 35% were heavily pretreated (≥ 2 prior lines of chemotherapy). The safety profile resembled previously known sunitinib malate toxicities. Median progression-free and overall survivals for liposarcoma, leiomyosarcoma, and MFH were 3.9 and 18.6, 4.2 and 10.1 and 2.5 and 13.6 months, respectively. The 3-month progression-free rates in the untreated and pretreated (chemotherapy) patients with liposarcoma, leiomyosarcoma and MFH were 75% and 69.2%, 60%, and 62.5% and 25% and 44.4%, respectively. With the caveats that a minority of patients with potentially indolent or low-grade disease could have been included and the small numbers, a 3-month progression-free rate of >40% suggests activity for sunitinib malate at least in liposarcomas and leiomyosarcomas. Thus, we believe that further investigation in these susceptible STS subtypes is warranted.


Asunto(s)
Indoles/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirroles/uso terapéutico , Sarcoma/tratamiento farmacológico , Supervivencia sin Enfermedad , Esquema de Medicación , Resistencia a Antineoplásicos , Femenino , Histiocitoma Fibroso Maligno/tratamiento farmacológico , Humanos , Indoles/efectos adversos , Leiomiosarcoma/tratamiento farmacológico , Liposarcoma/tratamiento farmacológico , Masculino , Metástasis de la Neoplasia , Inhibidores de Proteínas Quinasas/efectos adversos , Pirroles/efectos adversos , Recurrencia , Retratamiento , Sarcoma/patología , Sunitinib , Tasa de Supervivencia
15.
Cancer ; 117(19): 4484-92, 2011 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-21446046

RESUMEN

BACKGROUND: Patient outcomes following resection of colorectal liver metastases (CLM) after second-line chemotherapy regimen is unknown. METHODS: From August 1998 to June 2009, data from 1099 patients with CLM were collected prospectively. We retrospectively analyzed outcomes of patients who underwent resection of CLM after second-line (2 or more) chemotherapy regimens. RESULTS: Sixty patients underwent resection of CLM after 2 or more chemotherapy regimens. Patients had advanced CLM (mean number of CLM ± standard deviation, 4 ± 3.5; mean maximum size of CLM, 5 ± 3.2 cm) and had received 17 ± 8 cycles of preoperative chemotherapy. In 54 (90%) patients, the switch from the first regimen to another regimen was motivated by tumor progression or suboptimal radiographic response. All patients received irinotecan or oxaliplatin, and the majority (42/60 [70%]) received a monoclonal antibody (bevacizumab or cetuximab) as part of the last preoperative regimen. Postoperative morbidity and mortality rates were 33% and 3%, respectively. At a median follow-up of 32 months, 1-year, 3-year, and 5-year overall survival rates were 83%, 41%, and 22%, respectively. Median chemotherapy-free survival after resection or completion of additional chemotherapy administered after resection was 9 months (95% confidence interval, 4-14 months). Synchronous (vs metachronous) CLM and minor (vs major) pathologic response were independently associated with worse survival. CONCLUSIONS: Resection of CLM after a second-line chemotherapy regimen was found to be safe and was associated with a modest hope for definitive cure. This approach represents a viable option in patients with advanced CLM.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/cirugía , Hepatectomía/mortalidad , Neoplasias Hepáticas/cirugía , Complicaciones Posoperatorias , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales Humanizados , Bevacizumab , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Cetuximab , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Humanos , Irinotecán , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento
17.
Invest New Drugs ; 29(6): 1381-9, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-20644979

RESUMEN

PURPOSE: Triciribine phosphate is a potent, small-molecule inhibitor of activation of all three isoforms of AKT in vitro. AKT is an intracellular protein that, when activated, leads to cellular division; it is dysregulated in a large number of malignancies, and constitutively activating AKT mutations are present in a minority of cancers. PATIENTS AND METHODS: In this phase I study triciribine phosphate monohydrate (TCN-PM) was administered to subjects whose tumors displayed evidence of increased AKT phosphorylation (p-AKT) as measured by immunohistochemical analysis (IHC). TCN-PM was administered over 30 min on days 1, 8 and 15 of a 28-day cycle. Tumor biopsy specimens, collected before treatment and on day +15, were assessed for p-AKT by IHC and western blot analyses. RESULTS: Nineteen subjects were enrolled; 13 received at least one cycle of therapy, and a total of 34 complete cycles were delivered. One subject was treated at the 45 mg/m(2) dose before the study was closed due to its primary objective having been met. No dose-limiting toxic effects were observed. Modest decreases in tumor p-AKT following therapy with TCN-PM were observed at the 35 mg/m(2) and 45 mg/m(2) dose levels, although definitive conclusions were limited by the small sample size. CONCLUSIONS: These preliminary data suggest that treatment with TCN-PM inhibits tumor p-AKT at doses that were tolerable. Although single agent activity was not observed in this enriched population, further combination studies of TCN-PM with other signal transduction pathway inhibitors in solid tumors is warranted.


Asunto(s)
Acenaftenos/farmacología , Neoplasias/tratamiento farmacológico , Fosforilación/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ribonucleótidos/farmacología , Acenaftenos/efectos adversos , Acenaftenos/farmacocinética , Adulto , Biopsia , Relación Dosis-Respuesta a Droga , Humanos , Mutación , Neoplasias/patología , Ribonucleótidos/efectos adversos , Ribonucleótidos/farmacocinética , Resultado del Tratamiento
18.
Clin Child Psychol Psychiatry ; 26(3): 682-694, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33624515

RESUMEN

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.


Asunto(s)
Diabetes Mellitus Tipo 1 , Trastornos Mentales , Mentalización , Adolescente , Niño , Emociones , Humanos , Salud Mental , Apego a Objetos
19.
JBJS Case Connect ; 11(4)2021 11 22.
Artículo en Inglés | MEDLINE | ID: mdl-34807888

RESUMEN

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.


Asunto(s)
Huesos , Fémur , Adolescente , Adulto , Niño , Fémur/cirugía , Humanos , Masculino
20.
J Psychosom Res ; 150: 110634, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34610494

RESUMEN

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.


Asunto(s)
Diabetes Mellitus Tipo 1 , Hipoglucemia , Perfeccionismo , Adulto , Síntomas Afectivos/epidemiología , Concienciación , Estudios Transversales , Diabetes Mellitus Tipo 1/complicaciones , Humanos
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