RESUMEN
BACKGROUND: Immune checkpoint inhibitor (ICI) therapies have become increasingly popular treatment options for patients with cancer, even for patients in non-metastatic settings. Survival and responses have been reported for individual tumor types, but little is known about these outcomes, collectively. We sought to provide an overview of overall survival (OS) and progression-free survival (PFS) in ICI drugs tested in registration trials. METHODS: In a cross-sectional analysis of US FDA oncology ICI drug approvals (2011-2023), we searched for supporting ICI registration trials. We characterized these trials, regarding differences in median OS and PFS between patients in intervention and control arm participants in ICI registration trials; percentage of patients who receive ICI crossover; and whether there is correlation between the percentage of crossover and differences in OS or PFS. RESULTS: Fifty-six (54.4 %) approvals had trials that reported median OS for both intervention and control arms (median difference was 2.8 months; IQR: 2.2 to 5.0 months). Sixty-five (63.1 %) approvals had trials that reported PFS data for both arms (median of 0.9 months; IQR: -0.2 to 3.0 months). Subsequent therapy was common (median=18.9 %) and was significantly correlated with a higher difference in median OS in all studies with reported differences (R2 =0.15; p = 0.001). CONCLUSION: ICIs are increasingly used in the treatment of cancer, yet the median OS improvement is modest, and many ICIs have not been tested for OS benefit. OS is the outcome most meaningful for patients, and drug regulation should require better testing and reporting of these data.
Asunto(s)
Inhibidores de Puntos de Control Inmunológico , Neoplasias , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias/tratamiento farmacológico , Neoplasias/mortalidad , Estudios Transversales , Supervivencia sin Progresión , Aprobación de Drogas , Estados Unidos , Ensayos Clínicos como Asunto , Oncología Médica/métodosRESUMEN
BACKGROUND: The calcar of the proximal humerus is a fundamental structure for medial humeral column support. This study aimed to assess the outcome of osteosynthesis across cases of unstable proximal humerus fractures (PHFs) with medial calcar comminution, following treatment with a PHILOS locking plate and medial support screw (MSS). METHODS: Between January 2010 and December 2018, we retrospectively analyzed the outcomes of 121 cases of osteosynthesis for PHFs with medial column disruption. For the medial support, at least one oblique screw was inserted within 5 mm of the subchondral bone in the inferomedial quadrant of the humeral head. All patients were categorized into two groups: 26 patients in the single MSS group, and 95 in the multiple MSS group. Follow-up after at least an year involved clinical and radiographic outcome evaluations, and correspondingly measuring the Constant-Murley score, University of California, Los Angeles (UCLA) shoulder scale, pain visual analogue scale (VAS), major complications, neck-shaft angle (NSA), humeral head height (HHH), and the eventual time to bone union. Risk factors for the major complications were assessed by multivariate logistic regression analyses. RESULTS: The cohort's mean age was 64.4 ± 15.4 years, and the mean follow-up duration was 19.5 ± 7.6 months. At the final follow-up, between the single MSS and multiple MSS groups, no significant differences in the Constant-Murley score (p = 0.367), UCLA score (p = 0.558), VAS (p = 0.571), time to bone union (p = 0.621), NSA loss (p = 0.424), and HHH loss (p = 0.364) were observed. The incidence of complications (p = 0.446) based on the number of MSS were not significantly different. The initial insufficient reduction after surgery (of NSA < 125°) was found to be a significant risk factor for post-surgical complications. CONCLUSIONS: To treat unstable PHFs, the use of at least one MSS along with a locking plate system is sufficient to achieve satisfactory outcomes. Successful operative treatment using a locking plate for PHF treatment is inherent in anatomical fracture reduction, coupled with medial column support.
Asunto(s)
Placas Óseas , Tornillos Óseos , Fijación Interna de Fracturas , Fracturas del Hombro , Humanos , Fracturas del Hombro/cirugía , Fracturas del Hombro/diagnóstico por imagen , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Fijación Interna de Fracturas/instrumentación , Fijación Interna de Fracturas/métodos , Resultado del Tratamiento , Anciano de 80 o más Años , Estudios de Seguimiento , AdultoRESUMEN
Treatment of a comminuted proximal humerus fracture (PHF) in elderly patients with severe osteoporosis is challenging, often leading to arthroplasty (such as hemiarthroplasty or reverse shoulder arthroplasty) as the treatment of choice. However, arthroplasty does not always guarantee favorable outcomes. In contrast, the use of intramedullary fibular strut allografts provides additional reduction stability during locking plate fixation; however, to our knowledge, there is limited literature on the use of fibular strut allografts, including the fibular head. Here we aim to report the advantages of using a fibular strut containing the fibular head in severe osteoporotic PHFs. We present the case of an 88-year-old female patient with severe osteoporosis diagnosed with a left PHF accompanied by severe metaphyseal comminution following a fall from a chair. Rather than shoulder arthroplasty, we performed osteosynthesis using a fibular strut allograft containing the fibular head. At the one-year follow-up after surgery, we observed excellent bony union and a favorable functional outcome without major complications, such as reduction loss. The novel use of a fibular strut allograft containing the fibular head could be promising for PHFs with severe metaphyseal comminution, potentially avoiding the need for arthroplasty.
RESUMEN
BACKGROUND: The ideal treatment of terrble triad injuries and whether fixation of coronoid process fractures is needed or not are still debated. Therefore, we aimed to investigate if terrible triad injuries necessitate coronoid fracture fixation and evaluate if non-fixation treatments have similar efficacies and outcomes as fixation-treatments in cases of terrible triad injuries. METHODS: From August 2011 to July 2020, 23 patients with acute terrible triad injuries without involvement of the anteromedial facet of the coronoid process were included to evaluate the postoperative clinical and radiological outcomes (minimum follow-up of 20 months). According to the preoperative height loss evaluation of the coronoid process and an intraoperative elbow stability test, seven patients underwent coronoid fracture fixation, and the other eight patients were treated conservatively. The elbow range of motion (ROM), Mayo Elbow Performance Score (MEPS), and modified Broberg-Morrey score were evaluated at the last follow-up. In addition, plain radiographs were reviewed to evaluate joint congruency, fracture union, heterotopic ossification, and the development of arthritic changes. RESULTS: At the last follow-up, the mean arcs of flexion-extension and supination-pronation values were 118.2° and 146.8° in the fixation group and 122.5° and 151.3° in the non-fixation group, respectively. The mean MEPSs were 96.4 in the fixation group (excellent, nine cases; good, tow cases) and 96.7 in the non-fixation group (excellent, ten cases; good, two cases). The mean modified Broberg-Morrey scores were 94.0 in the fixation group (excellent, sevev cases; good, four cases) and 94.0 in the non-fixation group (excellent, ten cases; good, tow cases). No statistically significant differences in clinical scores and ROM were identified between the two groups. However, the non-fixation group showed a significantly lower height loss of the coronoid process than the fixation group (36.3% versus 54.5%). CONCLUSIONS: There were no significant differences in clinical outcomes between the fixation and non-fixation groups in terrible triad injuries.
Asunto(s)
Lesiones de Codo , Articulación del Codo , Fijación Interna de Fracturas , Rango del Movimiento Articular , Fracturas del Cúbito , Humanos , Masculino , Adulto , Femenino , Fracturas del Cúbito/cirugía , Fracturas del Cúbito/diagnóstico por imagen , Persona de Mediana Edad , Fijación Interna de Fracturas/métodos , Rango del Movimiento Articular/fisiología , Articulación del Codo/diagnóstico por imagen , Articulación del Codo/fisiopatología , Articulación del Codo/cirugía , Estudios Retrospectivos , Adulto Joven , Resultado del Tratamiento , Estudios de SeguimientoRESUMEN
ABSTRACT: Although Bruton tyrosine kinase inhibitors (BTKis) are generally well tolerated and less toxic than chemotherapy alternatives used to treat lymphoid malignancies, BTKis like ibrutinib have the potential to cause new or worsening hypertension (HTN). Little is known about the optimal treatment of BTKi-associated HTN. Randomly selected patients with lymphoid malignancies on a BTKi and antihypertensive drug(s) and with at least 3 months of follow-up data were sorted into 2 groups: those diagnosed with HTN before BTKi initiation (prior-HTN), and those diagnosed with HTN after BTKi initiation (de novo HTN). Generalized estimating equations assessed associations between time varying mean arterial pressures (MAPs) and individual anti-HTN drug categories. Of 196 patients included in the study, 118 had prior-HTN, and 78 developed de novo HTN. Statistically significant mean MAP reductions were observed in patients with prior-HTN who took ß blockers (BBs) with hydrochlorothiazide (HCTZ), (-5.05 mmHg; 95% confidence interval [CI], 10.0 to -0.0596; P = .047), and patients diagnosed with de novo HTN who took either an angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) with HCTZ (-5.47 mmHg; 95% CI, 10.9 to -0.001; P = .05). These regimens also correlated with the greatest percentages of normotensive MAPs. Treatment of HTN in patients taking a BTKi is challenging and may require multiple antihypertensives. Patients with prior-HTN appear to benefit from combination regimens with BBs and HCTZ, whereas patients with de novo HTN appear to benefit from ACEi/ARBs with HCTZ. These results should be confirmed in prospective studies.
Asunto(s)
Adenina , Antihipertensivos , Hipertensión , Piperidinas , Humanos , Adenina/análogos & derivados , Adenina/uso terapéutico , Adenina/efectos adversos , Piperidinas/uso terapéutico , Hipertensión/tratamiento farmacológico , Hipertensión/inducido químicamente , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Antihipertensivos/uso terapéutico , Antihipertensivos/efectos adversos , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/efectos adversos , Pirimidinas/uso terapéutico , Pirimidinas/efectos adversos , Pirazoles/uso terapéutico , Pirazoles/efectos adversos , Agammaglobulinemia Tirosina Quinasa/antagonistas & inhibidoresRESUMEN
BACKGROUND: Anatomical total shoulder arthroplasty (aTSA) has been used to manage degenerative diseases such as primary osteoarthritis. An increase in the use of this procedure has led to several developments in humeral and glenoid components to improve patient outcomes. This study aimed to compare clinical and radiological outcomes of the newly-introduced convertible metal-backed glenoid components with cemented polyethylene glenoid components in aTSA, and to determine whether the new component would be comparable to a conventional one for reducing the burden of future revision or conversion surgeries. METHODS: Medical records of fifty patients who underwent aTSA with at least two years of follow-up were retrospectively reviewed. Eighteen patients received convertible metal-backed glenoid components with vitamin E1-coated liner (MB group), while thirty-two patients received conventional cemented polyethylene glenoid components (PE group). Pre- and postoperative clinical and radiological outcomes (acromion-greater tuberosity angle [AGA] and humeral lateral offset [LO]) at final follow-up were assessed. Radiolucent lines (RLLs) and loosening around the humeral and glenoid components were also evaluated. RESULTS: Clinical outcomes improved after surgery in both groups (all p < 0.001). The arc of rotation measured by AGA improved postoperatively in both groups (all p < 0.001), and AGA and LO were not different according to the type of glenoid components (all p > 0.05). Overall complication rates including RLLs of PE and MB groups were 43.8% (14/32) and 16.7% (3/18), respectively (p = 0.031). Although the PE group had more RLLs than did the MB group (p < 0.05), related symptoms and/or glenoid implant loosening were not observed in both groups. Subscapularis failure occurred in two patients in the PE group and in one in the MB group. CONCLUSION: The convertible metal-backed glenoid implant with vitamin E1-coated liner may be a good alternative for considering the potential for an easier conversion to reverse total shoulder arthroplasty.
Asunto(s)
Artroplastía de Reemplazo de Hombro , Prótesis Articulares , Osteoartritis , Articulación del Hombro , Humanos , Polietileno , Articulación del Hombro/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Osteoartritis/cirugía , Diseño de Prótesis , Estudios de SeguimientoRESUMEN
BACKGROUND: Rank preserving structural failure time (RPSFT) is a statistical method to correct or adjust for crossover in clinical trials, by estimating the counterfactual effect on overall survival (OS) when control arm patients do not receive the interventional drug when their tumor progresses. We sought to examine the strength of correlation between differences in uncorrected and corrected OS hazard ratios and percentage of crossover, and characterize instances of fundamental and sequential efficacy. METHODS: In a cross-sectional analysis (2003-2023), we reviewed oncology randomized trials that used RPSFT analysis to adjust the OS hazard ratio for patients who crossed over to an anti-cancer drug. We calculated the percentage of RPSFT studies evaluating a drug for fundamental efficacy (with or without a standard of care (SOC)) or sequential efficacy and the correlation between the OS hazard ratio difference (unadjusted and adjusted) and the percentage of crossover. RESULTS: Among 65 studies, the median difference between the uncorrected and corrected OS hazard ratio was -0.1 (quartile 1, quartile 3 : -0.3 to -0.06). The median percentage of crossover was 56% (quartile 1, quartile 3: 37% to 72%). All studies were funded by the industry or had authors who were employees of the industry. Twelve studies (19%) tested a drug's fundamental efficacy when there was no SOC; 34 studies (52%) tested a drug's fundamental efficacy when there was already a SOC; and 19 studies (29%) tested a drug's sequential efficacy. The correlation between the uncorrected and corrected OS hazard ratio difference and the percentage of crossover was 0.44 (95% CI: 0.21 to 0.63). CONCLUSIONS: RPSFT is a common tactic used by the industry to reinterpret trial results. Nineteen percent of RPSFT use is appropriate. We recognize that while crossover can bias OS results, the allowance and handling of crossover in trials should be limited to appropriate circumstances.
Asunto(s)
Antineoplásicos , Neoplasias , Humanos , Estudios Transversales , Antineoplásicos/efectos adversos , Neoplasias/tratamiento farmacológico , Modelos de Riesgos ProporcionalesRESUMEN
BACKGROUND: Preeclampsia (PE) is known to arise from insufficient trophoblast invasion as uterine spiral arteries lack remodeling. A significant reduction in placental perfusion induces an ischemic placental microenvironment due to reduced oxygen delivery to the placenta and fetus, leading to oxidative stress. Mitochondria are involved in the regulation of cellular metabolism and the production of reactive oxygen species (ROS). NME/NM23 nuceloside diphosphate kinase 4 (NME4) gene is known to have the ability to supply nucleotide triphosphate and deoxynucleotide triphosphate for replication and transcription of mitochondria. Our study aimed to investigate changes in NME4 expression in PE using trophoblast stem-like cells (TSLCs) from induced pluripotent stem cells (iPSCs) as a model of early pregnancy and peripheral blood mononuclear cells (PBMNCs) as a model of late preterm pregnancy. METHODS: Transcriptome analysis using TSLCs was performed to identify the candidate gene associated with the possible pathophysiology of PE. Then, the expression of NME4 associated with mitochondrial function, p53 associated with cell death, and thioredoxin (TRX) linked to ROS were investigated through qRT-PCR, western blotting and deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick end labelling (TUNEL) assay. RESULTS: In patients with PE, NME4 was significantly downregulated in TSLCs but upregulated in PBMNCs. p53 was shown to be upregulated in TSLCs and PBMNCs of PE. In addition, western blot analysis confirmed that TRX expression had the tendency to increase in TSLCs of PE. Similarly, TUNEL analysis confirmed that the dead cells were higher in PE than in normal pregnancy. CONCLUSION: Our study showed that the expression of the NME4 differed between models of early and late preterm pregnancy of PE, and suggests that this expression pattern may be a potential biomarker for early diagnosis of PE.
Asunto(s)
Preeclampsia , Trofoblastos , Recién Nacido , Embarazo , Humanos , Femenino , Trofoblastos/metabolismo , Placenta/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Leucocitos Mononucleares/metabolismo , Nucleósido Difosfato Quinasa D/metabolismoRESUMEN
Importance: Idelalisib is a first-in-class phosphatidylinositol 3-kinase inhibitor that received US Food and Drug Administration accelerated approval in July 2014 as a single-agent treatment for relapsed follicular lymphoma (FL) and small lymphocytic lymphoma (SLL). Serious adverse effects were reported in 2016 leading to termination of postmarketing registry trials. However, idelalisib remained on the market until 2022 when Gilead voluntarily withdrew the drug for the accelerated approval indication. Objective: Evaluate the regulatory oversight of the accelerated approval pathway and evidence generation for idelalisib during premarketing (2008-2014), postmarketing (2014-2016), and premarketing withdrawal periods (2016-2022). Data Sources: ClinicalTrials.gov, FDA.gov, PubMed database. Study Selection: Clinical trials investigating the safety and effectiveness of idelalisib. Data Extraction and Synthesis: Study characteristics and relative risk (RR) of safety outcomes were abstracted. Data were pooled using random effects meta-analysis. The analysis was performed in October of 2022. Main Outcomes and Measures: Trial status, recruitment status, publication status, serious adverse events (SAEs), fatal adverse events (FAEs), and all-cause mortality. Results: Overall, 31 idelalisib trials met selection criteria. In total, 20 of 30 (65%) included SLL and/or FL; 13 (42%) trials were completed, 13 (42%) had published results, and 7 (23%) were randomized clinical trials (RCTs). Overall, 6 RCTs of idelalisib had publicly available data on safety outcomes. By the initial postmarketing period (2016), the cumulative RR for SAEs was 1.86 (95% CI, 1.63-2.11), for FAEs was 3.30 (95% CI, 1.56-7.00), and for death was 1.35 (95% CI, 0.85-2.12). In the premarketing withdrawal period, only a single phase 3 trial was enrolling patients for FL and was terminated. However, idelalisib was not withdrawn from the market until 2022. Gilead reported cumulative sales revenue of $842 million during market authorization (2014-2022) and annual sales had a steady decline from $168 million to $62 million during the premarketing withdrawal period (2016-2021). Conclusions and Relevance: Findings of this systematic review and meta-analysis show that serious risks of SAE, FAE, and death with idelalisib treatment were evident by 2016. However, idelalisib remained on the market for another 6 years, with minimal evidence generation. It was voluntarily withdrawn for FL and SLL accelerated approval indications coinciding with decreasing revenue generation. Closer attention for safety and effectiveness of drugs reaching market by accelerated approval is needed.
Asunto(s)
Leucemia Linfocítica Crónica de Células B , Linfoma no Hodgkin , Humanos , Linfoma no Hodgkin/tratamiento farmacológicoRESUMEN
The objective of this multicenter retrospective study was to examine the incidence, patient characteristics, pathology, and outcomes associated with Epstein-Barr virus (EBV)-related CNS lymphoma (CNSL) in older patients. Among 309 CNSL patients aged ≥60, 11.7% had EBV + tumors of which 72.2% were solid organ transplant (SOT)-related post-transplant lymphoproliferative disorders (PTLD). Younger age, SOT or autoimmune disease, and immunosuppressive treatment correlated highly with EBV-positivity. EBV + tumors were associated with absent C-MYC and BCL6 expression. EBV + PTLD was more likely to be associated with the absence of CD5 expression. EBV + non-PTLD had better median OS (not reached) compared to EBV + PTLD (10.8 months) and EBV-negative patients (43 months). Multivariable Cox regression analysis showed that age, performance status, and PTLD were negative predictors of OS. EBV status and immunosuppressive treatment were not correlated with OS. Our findings merit further investigation of EBV + PCNSL tumors and EBV-directed therapies.
Asunto(s)
Infecciones por Virus de Epstein-Barr , Linfoma , Trastornos Linfoproliferativos , Humanos , Anciano , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/epidemiología , Herpesvirus Humano 4 , Estudios Retrospectivos , Incidencia , Linfoma/etiología , Trastornos Linfoproliferativos/etiología , InmunosupresoresRESUMEN
There is a paucity of large-scale data delineating outcomes and prognostication of older patients with primary central nervous system lymphoma (PCNSL). We retrospectively analyzed 539 newly-diagnosed PCNSL patients ages ≥60 years across 20 U.S. academic centers. The median age was 70 years (range 60-88); at least one geriatric syndrome was present in 46%; the median Cumulative Index Ratings Scale-Geriatrics (CIRS-G) score was 6 (range, 0-27); and 36% had impairment in activities of daily living (ADL). The most common induction regimens were high-dose methotrexate (HD-MTX) ± rituximab; methotrexate, temozolomide, rituximab (MTR); and rituximab, methotrexate, procarbazine, vincristine (R-MPV). Overall, 70% of patients achieved remission, with 14% undergoing consolidative autologous stem cell transplant (ASCT) and 24% receiving maintenance. With 58-month median follow-up, median progression-free survival (PFS) and overall survival (OS) were 17 months (95% CI 13-22 months) and 43 months (95% CI 31-56 months), respectively. Three-year PFS and OS were highest with MTR (55% and 74%, respectively). With single-agent methotrexate ± rituximab, 3-year PFS and OS were 30% (p = .0002) and 47% (p = .0072). On multivariate analysis, increasing age at diagnosis and Cooperative Oncology Group (ECOG) performance status (PS) was associated with inferior PFS; age, hypoalbuminemia, higher CIRS-G score, and ECOG PS adversely affected OS. Among patients receiving maintenance, 3-year PFS was 65% versus 45% without maintenance (p = 0.02), with 3-year OS of 84% versus 61%, respectively (p = .0003). Altogether, outcomes in older PCNSL patients appeared optimized with HD-MTX combination induction regimens and maintenance therapy. Furthermore, several prognostic factors, including geriatric measures, were associated with inferior outcomes.
Asunto(s)
Neoplasias del Sistema Nervioso Central , Linfoma , Humanos , Anciano , Persona de Mediana Edad , Anciano de 80 o más Años , Rituximab/uso terapéutico , Metotrexato/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Citarabina , Actividades Cotidianas , Estudios Retrospectivos , Temozolomida/uso terapéutico , Linfoma/terapia , Sistema Nervioso Central/patología , Neoplasias del Sistema Nervioso Central/patologíaRESUMEN
Chronic rotator cuff tears (RCTs) are one of the most common injuries of shoulder pain. Despite the recent advances in surgical techniques and improved clinical outcomes of arthroscopically repaired rotator cuffs (RCs), complete functional recovery-without retear-of the RC tendon through tendon-to-bone interface (TBI) regeneration remains a key clinical goal to be achieved. Inspired by the highly organized nanostructured extracellular matrix in RC tendon tissue, we propose herein a tissue-engineered tendon nano-construct (TNC) for RC tendon regeneration. When compared with two currently used strategies (i.e., transosseous sutures and stem cell injections), our nano-construct facilitated more significant healing of all parts of the TBI (i.e., tendon, fibrocartilages, and bone) in both rabbit and pig RCT models owing to its enhancements in cell proliferation and differentiation, protein expression, and growth factor secretion. Overall, our findings demonstrate the high potential of this transplantable tendon nano-construct for clinical repair of chronic RCTs.
RESUMEN
Sinonasal malignancies make up <5% of all head and neck neoplasms, with an incidence of 0.5-1.0 per 100,000. The outcome of these rare malignancies has been poor, whereas significant progress has been made in the management of other cancers. The objective of the current review was to describe the incidence, causes, presentation, diagnosis, treatment, and recent developments of malignancies of the sinonasal tract. The diagnoses covered in this review included sinonasal undifferentiated carcinoma, sinonasal adenocarcinoma, sinonasal squamous cell carcinoma, and esthesioneuroblastoma, which are exclusive to the sinonasal tract. In addition, the authors covered malignances that are likely to be encountered in the sinonasal tract-primary mucosal melanoma, NUT (nuclear protein of the testis) carcinoma, and extranodal natural killer cell/T-cell lymphoma. For the purpose of keeping this review as concise and focused as possible, sarcomas and malignancies that can be classified as salivary gland neoplasms were excluded.
Asunto(s)
Carcinoma , Neoplasias del Seno Maxilar , Melanoma , Neoplasias Nasales , Senos Paranasales , Humanos , Carcinoma/diagnóstico , Neoplasias del Seno Maxilar/diagnóstico , Neoplasias del Seno Maxilar/patología , Cavidad Nasal/patología , Neoplasias Nasales/diagnóstico , Neoplasias Nasales/epidemiología , Neoplasias Nasales/terapia , Senos Paranasales/patologíaRESUMEN
OBJECTIVE: To review the epidemiology, presentation, diagnosis, and management of head and neck paragangliomas. METHODS: A literature review of english language papers with focus on most current literature. RESULTS: Paragangliomas (PGLs) are a group of neuroendocrine tumors that arise in the parasympathetic or sympathetic ganglia. Head and neck PGLs (HNPGLs) comprise 65% to 70% of all PGLs and account for 0.6% of all head and neck cancers. The majority of HNPGLs are benign, and 6% to 19% of all HNPGLs develop metastasis outside the tumor site and significantly compromise survival. PGLs can have a familial etiology with germline sequence variations in different susceptibility genes, with the gene encoding succinate dehydrogenase being the most common sequence variation, or they can arise from somatic sequence variations or fusion genes. Workup includes biochemical testing to rule out secretory components, although it is rare in HNPGLs. In addition, imaging modalities, such as computed tomography and magnetic resonance imaging, help in monitoring in surgical planning. Functional imaging with DOTATATE-positron emission tomography, 18F-fluorodeoxyglucose, or 18F-fluorohydroxyphenylalanine may be necessary to rule out sites of metastases. The management of HNPGLs is complex depending on pathology, location, and aggressiveness of the tumor. Treatment ranges from observation to resection to systemic treatment. Similarly, the prognosis ranges from a normal life expectancy to a 5-year survival of 11.8% in patients with distant metastasis. CONCLUSION: Our review is a comprehensive summary of the incidence, mortality, pathogenesis, presentation, workup and management of HNPGLs.
Asunto(s)
Neoplasias de Cabeza y Cuello , Paraganglioma Extraadrenal , Humanos , Fluorodesoxiglucosa F18 , Neoplasias de Cabeza y Cuello/diagnóstico , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/terapia , Paraganglioma/diagnóstico , Paraganglioma/epidemiología , Paraganglioma/genética , Paraganglioma/terapia , Paraganglioma Extraadrenal/diagnóstico , Paraganglioma Extraadrenal/epidemiología , Paraganglioma Extraadrenal/genética , Paraganglioma Extraadrenal/terapia , Succinato Deshidrogenasa/genética , Tomografía Computarizada por Rayos XRESUMEN
Histological analysis is widely used to evaluate injured tendons; however, it has the limitation of being semi-quantitative. Hence, we developed a quantification method to objectively evaluate the fibrous structure of tendons, exhibiting the optical property of birefringence, using polarization-sensitive optical coherence tomography (PS-OCT). We used a partial-rupture rat model in which the middle 0.75 cm of the Achilles tendon was cut with a blade. Rats were sacrificed at 2, 4 or 6 weeks after the injury, and PS-OCT and histological analyzes were performed. The PS-OCT phase retardation images and score well represented the structural changes of the injured tendon according to the wound healing state. Therefore, the proposed novel quantification method using PS-OCT can be used to evaluate the fibrous structural status of tendons.
Asunto(s)
Tendón Calcáneo , Tomografía de Coherencia Óptica , Ratas , Animales , Birrefringencia , Tomografía de Coherencia Óptica/métodos , Tendón Calcáneo/diagnóstico por imagen , Cicatrización de HeridasRESUMEN
This study investigated the neuropsychological profile of college students who engage in binge drinking (BD) using comprehensive neuropsychological tests evaluating verbal/non-verbal memory, executive functions, and attention. Groups were determined based on scores on the Korean version of the Alcohol Use Disorder Identification Test (AUDIT-K) and Alcohol Use Questionnaire (AUQ). There were 79 and 81 participants in the BD and non-BD groups, respectively. We administered the Korean version of the California Verbal Learning Test (K-CVLT) and Rey-Osterrieth Complex Figure Test (RCFT) to evaluate verbal and non-verbal memory, respectively, and measured executive functions using the Wisconsin Card Sorting Test (WCST), Trail-Making Test, Controlled Oral Word Association Test and Stroop Color-Word Test. We administered the d2 test to evaluate attention. Neuropsychological performance was analyzed by multivariate analysis of variance. The BD group showed significantly poorer performance in the long-term free recall condition of the K-CVLT and delayed recall condition of the RCFT and completed significantly fewer categories on the WCST than the non-BD group. In addition, there were significant negative associations among the AUDIT-K total score, AUQ binge score, and long-term free recall score of the K-CVLT. There were significant negative associations between the total AUDIT-K score and delayed recall RCFT score, and between the total AUDIT-K total score and numbers of completed categories on the WCST. These results indicate that college students who participate in BD have difficulties with verbal/non-verbal memory and executive functions, and further suggest that excessive alcohol use could have detrimental effects on the hippocampal-prefrontal circuit even with a relatively short period of alcohol use.