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1.
Pediatr Nephrol ; 38(12): 3947-3954, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-36625931

RESUMO

The International Study of Kidney Disease in Children (ISKDC), begun in 1966, conducted the first international collaborative randomized blinded controlled trial in pediatric nephrology and one of the first in either pediatrics or nephrology. For this trial, the ISKDC developed the criteria, such as those for response and relapse, used today to describe the clinical course of the nephrotic syndrome, and the trial generated the nephropathologic terminology and criteria which largely remain the current standards. Over an approximately 20-year span, the ISKDC followed the natural history and evaluated the therapeutic effectiveness of therapies in over 500 children with the nephrotic syndrome from three continents. It published 14 peer-reviewed studies and several reports and commentaries, many of which helped create current standards of practice for therapy of childhood nephrotic syndrome and consequently remain highly cited today. The ISKDC continues to be an important model for subsequent collaborative studies and was the impetus for the development of regional and national pediatric nephrology societies leading to the recognition and growth of pediatric nephrology as a separate subspecialty. A higher resolution version of the Graphical abstract is available as Supplementary information.


Assuntos
Nefropatias , Nefrologia , Síndrome Nefrótica , Criança , Humanos , Síndrome Nefrótica/terapia , Síndrome Nefrótica/tratamento farmacológico , Nefropatias/terapia , Nefropatias/tratamento farmacológico , Recidiva , Esquema de Medicação
2.
J Acoust Soc Am ; 154(1): 323-333, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37450331

RESUMO

Smartphone technology has been used for at-home health monitoring, but there are few available applications (apps) for tracking acoustic measures of voice for those with chronic voice problems. Current apps limit the user by restricting the range of smartphone positions to those that are unnatural and non-interactive. Therefore, we aimed to understand how more natural smartphone positions impacted the accuracy of acoustic measures in comparison to clinically acquired and derived measures. Fifty-six adults (11 vocally healthy, 45 voice disordered, aged 18-80 years) completed voice recordings while holding their smartphones in four different positions (e.g., as if reading from the phone, up to the ear, etc.) while a head-mounted high-quality microphone attached to a handheld acoustic recorder simultaneously captured voice recordings. Comparisons revealed that mean fundamental frequency (Hz), maximum phonation time (s), and cepstral peak prominence (CPP; dB) were not impacted by phone position; however, CPP was significantly lower on smartphone recordings than handheld recordings. Spectral measures (low-to-high spectral ratio, harmonics-to-noise ratio) were impacted by the phone position and the recording device. These results indicate that more natural phone positions can be used to capture specific voice measures, but not all are directly comparable to clinically derived values.


Assuntos
Smartphone , Acústica da Fala , Qualidade da Voz , Acústica
3.
Am J Kidney Dis ; 77(2): 216-225, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32791086

RESUMO

RATIONALE & OBJECTIVE: Remission of proteinuria has been shown to be associated with lower rates of kidney disease progression among people with focal segmental glomerulosclerosis (FSGS). The goal of this study was to evaluate whether reductions in proteinuria after treatment are associated with greater kidney survival. STUDY DESIGN: Cohort analysis of clinical trial participants. SETTING & PARTICIPANTS: Patients with steroid-resistant FSGS enrolled in a randomized treatment trial that compared cyclosporine with mycophenolate mofetil plus dexamethasone. PREDICTORS: Reduction in proteinuria measured during 26 weeks after initiating treatment. OUTCOMES: Repeated assessments of estimated glomerular filtration rate (eGFR) and time to a composite outcome of kidney failure or death assessed between 26 weeks and 54 months after randomization. ANALYTICAL APPROACH: Multivariable linear mixed-effects models with participant-specific slope and intercept to estimate the association of change in proteinuria over 26 weeks while receiving treatment with the subsequent slope of change in eGFR. Multivariable time-varying Cox proportional hazards models were used to estimate the association of changes in proteinuria with time to the composite outcome. RESULTS: 138 of 192 trial participants were included. Changes in proteinuria over 26 weeks were significantly related to eGFR slope. A 1-unit reduction in log-transformed urinary protein-creatinine ratio was associated with a 3.90mL/min/1.73m2 per year increase in eGFR (95% CI, 2.01-5.79). This difference remained significant after adjusting for complete remission. There was an analogous relationship between time-varying proteinuria and time to the composite outcome: the HR per 1-unit reduction in log-transformed urinary protein-creatinine ratio was 0.23 (95% CI, 0.12-0.44). LIMITATIONS: Limited to individuals with steroid-resistant FSGS followed up for a maximum of 5 years. CONCLUSIONS: These findings provide evidence for the benefit of urinary protein reduction in FSGS. Reductions in proteinuria warrant further evaluation as a potential surrogate for preservation of kidney function that may inform the design of future clinical trials.


Assuntos
Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Glomerulosclerose Segmentar e Focal/urina , Glucocorticoides/uso terapêutico , Imunossupressores/uso terapêutico , Falência Renal Crônica/epidemiologia , Proteinúria/urina , Adolescente , Criança , Estudos de Coortes , Creatinina/urina , Ciclosporina/uso terapêutico , Dexametasona/uso terapêutico , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Mortalidade , Ácido Micofenólico/uso terapêutico , Prognóstico , Modelos de Riscos Proporcionais , Indução de Remissão , Sobrevivência de Tecidos , Resultado do Tratamento , Adulto Jovem
4.
Phys Rev Lett ; 127(23): 230602, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34936767

RESUMO

We investigate the spectral and transport properties of many-body quantum systems with conserved charges and kinetic constraints. Using random unitary circuits, we compute ensemble-averaged spectral form factors and linear-response correlation functions, and find that their characteristic timescales are given by the inverse gap of an effective Hamiltonian-or equivalently, a transfer matrix describing a classical Markov process. Our approach allows us to connect directly the Thouless time, t_{Th}, determined by the spectral form factor, to transport properties and linear-response correlators. Using tensor network methods, we determine the dynamical exponent z for a number of constrained, conserving models. We find universality classes with diffusive, subdiffusive, quasilocalized, and localized dynamics, depending on the severity of the constraints. In particular, we show that quantum systems with "Fredkin" constraints exhibit anomalous transport with dynamical exponent z≃8/3.

5.
Pediatr Nephrol ; 35(10): 1835-1841, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-31654223
6.
Phys Rev Lett ; 123(17): 170603, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31702243

RESUMO

We construct an interacting integrable Floquet model featuring quasiparticle excitations with topologically nontrivial chiral dispersion. This model is a fully quantum generalization of an integrable classical cellular automaton. We write down and solve the Bethe equations for the generalized quantum model and show that these take on a particularly simple form that allows for an exact solution: essentially, the quasiparticles behave like interacting hard rods. The generalized thermodynamics and hydrodynamics of this model follow directly, providing an exact description of interacting chiral particles in the thermodynamic limit. Although the model is interacting, its unusually simple structure allows us to construct operators that spread with no butterfly effect; this construction does not seem possible in other interacting integrable systems. This model exemplifies a new class of exactly solvable, interacting quantum systems specific to the Floquet setting.

7.
Phys Rev Lett ; 123(21): 210603, 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31809174

RESUMO

We investigate spectral statistics in spatially extended, chaotic many-body quantum systems with a conserved charge. We compute the spectral form factor K(t) analytically for a minimal Floquet circuit model that has a U(1) symmetry encoded via spin-1/2 degrees of freedom. Averaging over an ensemble of realizations, we relate K(t) to a partition function for the spins, given by a Trotterization of the spin-1/2 Heisenberg ferromagnet. Using Bethe ansatz techniques, we extract the "Thouless time" t_{Th} demarcating the extent of random matrix behavior, and find scaling behavior governed by diffusion for K(t) at t≲t_{Th}. We also report numerical results for K(t) in a generic Floquet spin model, which are consistent with these analytic predictions.

8.
J Am Soc Nephrol ; 26(6): 1443-8, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25573908

RESUMO

Genetic variants in apolipoprotein L1 (APOL1) confer risk for kidney disease. We sought to better define the phenotype of APOL1-associated nephropathy. The FSGS Clinical Trial involved 138 children and young adults who were randomized to cyclosporin or mycophenolate mofetil plus pulse oral dexamethasone with a primary outcome of proteinuria remission. DNA was available from 94 subjects who were genotyped for APOL1 renal risk variants, with two risk alleles comprising the risk genotype. Two APOL1 risk alleles were present in 27 subjects, of whom four subjects did not self-identify as African American, and 23 of 32 (72%) self-identified African Americans. Individuals with the APOL1 risk genotype tended to present at an older age and had significantly lower baseline eGFR, more segmental glomerulosclerosis and total glomerulosclerosis, and more tubular atrophy/interstitial fibrosis. There were differences in renal histology, particularly more collapsing variants in those with the risk genotype (P=0.02), although this association was confounded by age. APOL1 risk genotype did not affect response to either treatment regimen. Individuals with the risk genotype were more likely to progress to ESRD (P<0.01). In conclusion, APOL1 risk genotypes are common in African-American subjects with primary FSGS and may also be present in individuals who do not self-identify as African American. APOL1 risk status is associated with lower kidney function, more glomerulosclerosis and interstitial fibrosis, and greater propensity to progress to ESRD. The APOL1 risk genotype did not influence proteinuria responses to cyclosporin or mycophenolate mofetil/dexamethasone.


Assuntos
Apolipoproteínas/genética , Ciclosporinas/uso terapêutico , Dexametasona/uso terapêutico , Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Glomerulosclerose Segmentar e Focal/genética , Lipoproteínas HDL/genética , Ácido Micofenólico/análogos & derivados , Adolescente , Adulto , Apolipoproteína L1 , Criança , Feminino , Seguimentos , Regulação da Expressão Gênica , Genótipo , Glomerulosclerose Segmentar e Focal/diagnóstico , Glomerulosclerose Segmentar e Focal/mortalidade , Humanos , Testes de Função Renal , Masculino , Ácido Micofenólico/uso terapêutico , Estudos Prospectivos , Medição de Risco , Índice de Gravidade de Doença , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
9.
Mol Psychiatry ; 19(12): 1275-1283, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24514565

RESUMO

Stress can exert long-lasting changes on the brain that contribute to vulnerability to mental illness, yet mechanisms underlying this long-term vulnerability are not well understood. We hypothesized that stress may alter the production of oligodendrocytes in the adult brain, providing a cellular and structural basis for stress-related disorders. We found that immobilization stress decreased neurogenesis and increased oligodendrogenesis in the dentate gyrus (DG) of the adult rat hippocampus and that injections of the rat glucocorticoid stress hormone corticosterone (cort) were sufficient to replicate this effect. The DG contains a unique population of multipotent neural stem cells (NSCs) that give rise to adult newborn neurons, but oligodendrogenic potential has not been demonstrated in vivo. We used a nestin-CreER/YFP transgenic mouse line for lineage tracing and found that cort induces oligodendrogenesis from nestin-expressing NSCs in vivo. Using hippocampal NSCs cultured in vitro, we further showed that exposure to cort induced a pro-oligodendrogenic transcriptional program and resulted in an increase in oligodendrogenesis and decrease in neurogenesis, which was prevented by genetic blockade of glucocorticoid receptor (GR). Together, these results suggest a novel model in which stress may alter hippocampal function by promoting oligodendrogenesis, thereby altering the cellular composition and white matter structure.


Assuntos
Diferenciação Celular/fisiologia , Corticosterona/metabolismo , Glucocorticoides/metabolismo , Hipocampo/fisiologia , Oligodendroglia/fisiologia , Estresse Psicológico/fisiopatologia , Animais , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Células Cultivadas , Corticosterona/administração & dosagem , Modelos Animais de Doenças , Glucocorticoides/administração & dosagem , Hipocampo/efeitos dos fármacos , Masculino , Camundongos Transgênicos , Nestina/genética , Nestina/metabolismo , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/fisiologia , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Oligodendroglia/efeitos dos fármacos , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Receptores de Glucocorticoides/antagonistas & inibidores , Receptores de Glucocorticoides/metabolismo , Restrição Física
10.
Adv Exp Med Biol ; 872: 235-52, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26215997

RESUMO

In this chapter, we describe the central role of the brain in the glucocorticoid mediated stress response. We describe the mechanisms by which the brain gauges the severity of stress, mechanisms of hypothalamic-pituitary-adrenal axis (HPA) regulation, and how various sub-systems of the brain respond to glucocorticoid (GC) signaling to regulate stress behavior. In particular, we focus on the hippocampus, pre-frontal cortex, and amygdala, where GCs can induce a series of changes. Finally, we briefly discuss an apparent paradox in GC signaling: while exposure to glucocorticoids promotes the survival of an organism during acute stress, these same hormones in chronic excess can also cause damage and promote illness.


Assuntos
Encéfalo/fisiologia , Glucocorticoides/fisiologia , Estresse Fisiológico , Animais , Humanos
11.
J Nat Prod ; 77(1): 92-9, 2014 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-24364476

RESUMO

A number of marine natural products are potent inhibitors of proteases, an important drug target class in human diseases. Hence, marine cyanobacterial extracts were assessed for inhibitory activity to human cathepsin L. Herein, we have shown that gallinamide A potently and selectively inhibits the human cysteine protease cathepsin L. With 30 min of preincubation, gallinamide A displayed an IC50 of 5.0 nM, and kinetic analysis demonstrated an inhibition constant of ki = 9000 ± 260 M(-1) s(-1). Preincubation-dilution and activity-probe experiments revealed an irreversible mode of inhibition, and comparative IC50 values display a 28- to 320-fold greater selectivity toward cathepsin L than closely related human cysteine cathepsin V or B. Molecular docking and molecular dynamics simulations were used to determine the pose of gallinamide in the active site of cathepsin L. These data resulted in the identification of a pose characterized by high stability, a consistent hydrogen bond network, and the reactive Michael acceptor enamide of gallinamide A positioned near the active site cysteine of the protease, leading to a proposed mechanism of covalent inhibition. These data reveal and characterize the novel activity of gallinamide A as a potent inhibitor of human cathepsin L.


Assuntos
Catepsina L/antagonistas & inibidores , Cianobactérias/química , Peptídeos/farmacologia , Inibidores de Proteases/farmacologia , Sequência de Aminoácidos , Peptídeos Catiônicos Antimicrobianos , Domínio Catalítico , Catepsina L/metabolismo , Humanos , Concentração Inibidora 50 , Cinética , Biologia Marinha , Estrutura Molecular , Peptídeos/química , Inibidores de Proteases/isolamento & purificação
12.
Ann Otol Rhinol Laryngol ; 123(3): 188-94, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24633945

RESUMO

OBJECTIVES: Mandibular tori have been identified as a contributing factor in difficult exposure during intubation. However, no investigation has measured the effect of mandibular tori on glottic exposure during suspension microlaryngoscopy (SML). The objective of this study was to measure how the size and location of mandibular tori affect glottic exposure during simulated SML at different thyromental distances. METHODS: Suspension microlaryngoscopy was modeled on an anatomically accurate skull and larynx with thyromental distances between 6 and 12 cm. Mandibular tori were simulated by protruding screws 5 to 15 mm from the lingual aspect of the mandible. The tori were positioned either 15 mm (anterior) or 25 mm (posterior) from the midline of the symphysis. The glottic exposure for the various-size tori in each location was measured by recording the displacement of the glottiscope tip relative to the most anterior exposure achievable without tori. The glottiscope angle relative to the horizontal plane was measured for each condition. RESULTS: Mandibular tori of more than 10 mm had a significant impact on glottic exposure. Displacement of the glottiscope tip ranged from 2 to 9 mm for anteriorly placed tori and from 7 to 29 mm for posteriorly placed tori, with larger tori causing greater displacement. Increasing the thyromental distance increased the posterior glottiscope tip displacement regardless of torus size or location. The glottiscope angle increased with larger tori (12º to 28º), but this angle did not change with increasing thyromental distance. CONCLUSIONS: Larger size and more-posterior location of mandibular tori more significantly reduce glottic exposure during SML. The inner table of the mandible is the most relevant anatomic constraint on glottic exposure, which varies with the presence or absence of mandibular tori independent of thyromental distance.


Assuntos
Exostose/complicações , Glote/cirurgia , Laringoscopia/métodos , Doenças Mandibulares/complicações , Microcirurgia/métodos , Glote/patologia , Humanos , Modelos Anatômicos
13.
Laryngoscope ; 134(1): 97-102, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37191092

RESUMO

OBJECTIVE: To compare improvement in patient-reported outcomes (PROM) in persons undergoing endoscopic and open surgical management of Zenker diverticula (ZD). METHODOLOGY: Prospective, multicenter cohort study of all individuals enrolled in the Prospective OUtcomes of Cricopharyngeus Hypertonicity (POUCH) Collaborative who underwent surgery for ZD. Patient survey, radiography reports, and the 10-item Eating Assessment Tool (EAT-10) pre- and post-procedure were abstracted from a REDCap database, which summarized means, medians, percentages, and frequencies of. Outcome based on operative intervention (endoscopic vs. open) was compared using t-test, Wilcoxon rank sum test or chi-square test, as appropriate. RESULTS: One hundred and forty-seven persons were prospectively followed. The mean age (SD) of the cohort was 68.7 (11.0). Overall, 66% of patients reported 100% improvement in EAT-10; 81% of patients had greater than 75% improvement; and 88% had greater than 50% improvement. Endoscopic was used for n = 109 patients, and open surgical intervention was used for n = 38. The median [interquartile range, IQR] EAT-10 percent improvement for endoscopic treatment was 93.3% [72, 100], and open was 100% [92.3, 100] (p = 0.05). The incidence of intraoperative complications was 3.7% for endoscopic and 7.9% for open surgical management. The median [IQR] in follow-up was 86 and 97.5 days, respectively. CONCLUSION: Both endoscopic and open surgical management of ZD provide significant improvement in patient-reported outcomes. The data suggest that open diverticulectomy may provide a modest advantage in symptomatic improvement compared to endoscopic management. The data suggest that the postoperative complication rate is higher in the open surgical group. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:97-102, 2024.


Assuntos
Divertículo de Zenker , Humanos , Estudos de Coortes , Esofagoscopia , Estudos Longitudinais , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento , Divertículo de Zenker/cirurgia , Pessoa de Meia-Idade , Idoso
14.
Laryngoscope ; 134(6): 2678-2683, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38146791

RESUMO

OBJECTIVES: The aim of the study was to identify trends in postoperative management of persons undergoing surgery for Zenker diverticula (ZD) by evaluating length of stay (LOS), diet on discharge, and imaging with or without surgical complication. METHODS: Prospectively enrolled adult patients with cricopharyngeal muscle dysfunction with diverticula undergoing surgery from August 1, 2017 to February 1, 2023 were included. Data were extracted from a multi-institutional REDCap database, summarizing means, medians, percentages, and frequencies. Fisher's exact or chi squared analyses were utilized, as appropriate, to compare subsets of data. Descriptive analysis assessed differences in clinical course and the relationship to postoperative management. RESULTS: There were 298 patients with a mean (standard deviation) age of 71.8 (11.2) years and 60% male. Endoscopic surgery was performed in 79.5% (237/298) of patients versus 20.5% (61/298) open surgery. Sixty patients (20.1%) received postoperative imaging, with four leaks identified. Complications were identified in 9.4% of cases (n = 29 complications in 28 patients), more commonly in open surgery. Most (81.2%) patients were discharged within 23 h. About half of patients (49%) were discharged from the hospital on a pureed/liquid diet; 36% had been advanced to a soft diet. In patients without complications, LOS was significantly longer following open cases (p = 0.002); postoperative diet was not different between open and endoscopic (p = 0.26). CONCLUSIONS: Overall, most patients are discharged within 23 h without imaging. However, LOS was affected by surgical approach. Postoperative complications are different in endoscopic versus open surgery. Complications with either approach were associated with prolonged LOS, need for imaging, and diet restriction. LEVEL OF EVIDENCE: Level III Laryngoscope, 134:2678-2683, 2024.


Assuntos
Tempo de Internação , Cuidados Pós-Operatórios , Complicações Pós-Operatórias , Divertículo de Zenker , Humanos , Masculino , Divertículo de Zenker/cirurgia , Divertículo de Zenker/complicações , Feminino , Idoso , Tempo de Internação/estatística & dados numéricos , Estudos Prospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Cuidados Pós-Operatórios/métodos , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Músculos Faríngeos/cirurgia , Resultado do Tratamento
15.
J Chem Inf Model ; 53(7): 1726-35, 2013 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-23734946

RESUMO

We compare established docking programs, AutoDock Vina and Schrödinger's Glide, to the recently published NNScore scoring functions. As expected, the best protocol to use in a virtual-screening project is highly dependent on the target receptor being studied. However, the mean screening performance obtained when candidate ligands are docked with Vina and rescored with NNScore 1.0 is not statistically different than the mean performance obtained when docking and scoring with Glide. We further demonstrate that the Vina and NNScore docking scores both correlate with chemical properties like small-molecule size and polarizability. Compensating for these potential biases leads to improvements in virtual screen performance. Composite NNScore-based scoring functions suited to a specific receptor further improve performance. We are hopeful that the current study will prove useful for those interested in computer-aided drug design.


Assuntos
Bases de Dados de Produtos Farmacêuticos , Avaliação Pré-Clínica de Medicamentos/métodos , Redes Neurais de Computação , Humanos , Simulação de Acoplamento Molecular , Curva ROC , Software
16.
Ann Otol Rhinol Laryngol ; 122(3): 151-8, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23577566

RESUMO

OBJECTIVES: Surgery and radiotherapy routinely provide high cure rates in treating early glottic cancer. Therefore, key metrics for success are optimal voice outcome and preservation of future cancer treatment options. Remarkably, there is a paucity of pretreatment versus posttreatment voice outcome data. Angiolytic KTP (potassium titanyl phosphate) laser treatment of early glottic cancer with ultranarrow margins was initiated to better preserve vocal function. Given that effective oncological results have been achieved, it was hypothesized that this approach would also result in improved posttreatment measures of vocal function that more closely approximate historical norms than pretreatment values. METHODS: Pretreatment and posttreatment voice outcome data were obtained for 92 patients (64 with T1 cancer and 28 with T2 cancer) who underwent 532-nm KTP laser treatment of early glottic cancer in a study design in which each patient essentially served as his or her own control. The evaluations included objective measures (acoustic and aerodynamic) and patients' self-assessments of vocal function (Voice-Related Quality of Life; V-RQOL). A series of mixed analyses of variance were conducted for all vocal function measures, with tumor stage and depth of invasion as the between-subjects variables and time (presurgery versus postsurgery) as the within-subject variable. RESULTS: There were statistically significant (p < or = 0.05) postoperative improvements for acoustic (perturbation and noise-to-harmonics ratio) and aerodynamic (subglottic pressure and vocal efficiency) measures of vocal function, as well as for V-RQOL assessment. CONCLUSIONS: Comprehensive pretreatment and posttreatment voice measures in a large patient cohort demonstrated that the KTP laser significantly improved postoperative vocal function in patients with early glottic cancer. Furthermore, radiotherapy was preserved as an oncological treatment option.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Glote/cirurgia , Neoplasias de Cabeça e Pescoço/cirurgia , Neoplasias Laríngeas/cirurgia , Laringoscopia/métodos , Lasers de Estado Sólido/uso terapêutico , Voz , Acústica , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Neoplasias Laríngeas/patologia , Laringoscopia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Resultado do Tratamento , Distúrbios da Voz/etiologia , Qualidade da Voz , Adulto Jovem
17.
Ann Otol Rhinol Laryngol ; 122(4): 235-9, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23697320

RESUMO

OBJECTIVES: Management of early glottic cancer subsequent to failed radiotherapy is challenging, especially in balancing oncological control and function preservation. Patients frequently have been incentivized against surgical management and thus have undergone radiotherapy as initial treatment. This history compounds the difficulty of discussions about surgical management after recurrence. Typically, endoscopic salvage has less morbidity than transcervical partial laryngectomy and is clearly desirable over total laryngectomy. However, there are appropriate concerns about the efficacy of endoscopic salvage and the overarching impact on larynx preservation and survival. Given our success with endoscopic angiolytic KTP laser treatment of previously nonirradiated T1 and T2 glottic cancers, we examined our results from treating similar-sized lesions after failed radiotherapy. METHODS: We performed a retrospective chart review of 20 patients from our cancer database who had undergone failed radiation therapy elsewhere for early glottic cancer and then underwent endoscopic angiolytic KTP laser treatment. RESULTS: Analysis of the geographic tumor recurrence of the 20 patients revealed T1a N0 M0 cancer in 4 patients, T1b N0 M0 cancer in 1 patient, T2a N0 M0 cancer in 1 patient, and T2b N0 M0 cancer in 14 patients. After KTP laser salvage treatment, 4 patients (20%) had local recurrence (all T2b) and required subsequent total laryngectomy, and 3 of these patients (15%) ultimately died of disease. The remaining 16 patients (80%) were free of disease at least 2 years after endoscopic salvage (average follow-up, 39 months). CONCLUSIONS: Our investigation provides preliminary evidence that angiolytic KTP laser salvage treatment of early glottic cancer is an effective treatment after failed irradiation. Studies with larger cohorts and longer follow-up will be necessary to establish incontrovertible evidence of its efficacy.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Glote/cirurgia , Neoplasias de Cabeça e Pescoço/cirurgia , Neoplasias Laríngeas/cirurgia , Laringoscopia/métodos , Lasers de Estado Sólido/uso terapêutico , Terapia de Salvação/métodos , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/irrigação sanguínea , Carcinoma de Células Escamosas/radioterapia , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/irrigação sanguínea , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Neoplasias Laríngeas/irrigação sanguínea , Neoplasias Laríngeas/radioterapia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Resultado do Tratamento
18.
J Am Soc Nephrol ; 23(12): 2051-9, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23138488

RESUMO

Overexpression of soluble urokinase receptor (suPAR) causes pathology in animal models similar to primary FSGS, and one recent study demonstrated elevated levels of serum suPAR in patients with the disease. Here, we analyzed circulating suPAR levels in two cohorts of children and adults with biopsy-proven primary FSGS: 70 patients from the North America-based FSGS clinical trial (CT) and 94 patients from PodoNet, the Europe-based consortium studying steroid-resistant nephrotic syndrome. Circulating suPAR levels were elevated in 84.3% and 55.3% of patients with FSGS patients in the CT and PodoNet cohorts, respectively, compared with 6% of controls (P<0.0001); inflammation did not account for this difference. Multiple regression analysis suggested that lower suPAR levels associated with higher estimated GFR, male sex, and treatment with mycophenolate mofetil. In the CT cohort, there was a positive association between the relative reduction of suPAR after 26 weeks of treatment and reduction of proteinuria, with higher odds for complete remission (P=0.04). In the PodoNet cohort, patients with an NPHS2 mutation had higher suPAR levels than those without a mutation. In conclusion, suPAR levels are elevated in geographically and ethnically diverse patients with FSGS and do not reflect a nonspecific proinflammatory milieu. The associations between a change in circulating suPAR with different therapeutic regimens and with remission support the role of suPAR in the pathogenesis of FSGS.


Assuntos
Glomerulosclerose Segmentar e Focal/sangue , Receptores de Ativador de Plasminogênio Tipo Uroquinase/sangue , Adolescente , Proteína C-Reativa/metabolismo , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Humanos , Imunossupressores/uso terapêutico , Masculino , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto Jovem
19.
Laryngoscope ; 133(4): 901-907, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-35852500

RESUMO

OBJECTIVE: Limited investigation of factors potentially contributing to treatment choice in early-stage glottic carcinoma (EGC) has been performed with large-scale data. The National Cancer Database (NCDB) represents >72% of all new cancer cases in the United States. We hypothesized that NCDB variables may lend insight into treatment decisions between surgery and radiation for EGC. METHODS: The NCDB was queried for all cases of T1-2  N0  M0 glottic carcinoma from 2004 to 2016. We used multivariable logistic regression analysis to examine factors associated with first-line treatment modality: radiation therapy (RT) versus surgery. All reported odds ratios (OR) were adjusted for age, gender, race, insurance, residence in a metropolitan area, region, and facility volume. RESULTS: 34,991 EGC patients received treatment: 6,687 (19%) surgery; 20,289 (58%) RT; and 8,015 (23%) surgery and RT. OR for receiving RT (vs. surgery alone) were >2 for: more advanced T stage cancers (OR 2.5 [95%CI: 2.3, 2.7]), treatment at non-academic facilities (OR 2.8, [95%CI: 2.6, 3.0]), and shorter travel distances to treatment centers (OR 2.2, [95%CI: 2.0, 2.4]). Surgery was more likely with treatment in the western US, higher income, private insurance, living in a metropolitan (vs. non-metropolitan) area, female gender, older age, and low facility volume. Hispanic ethnicity, education level, and race were not associated with treatment type in the multivariable model. CONCLUSION: Most patients in the NCDB receive first-line treatment with radiation for EGC, and this decision is associated with various tumor, patient, and treatment facility characteristics. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:901-907, 2023.


Assuntos
Carcinoma , Neoplasias Laríngeas , Humanos , Feminino , Estados Unidos , Neoplasias Laríngeas/epidemiologia , Neoplasias Laríngeas/terapia , Neoplasias Laríngeas/patologia , Terapia Combinada , Demografia
20.
Laryngoscope ; 133(12): 3492-3498, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37334783

RESUMO

OBJECTIVE: Receiving instruments from surgical technicians during endoscopic laryngeal and airway microsurgery (ELAM) has challenges including repeated, expeditious handling of delicate instruments and passing them to the surgeon's hand opposite of where the surgical assistant is standing. Optimizing this interaction may reduce surgical errors and improve operative efficiency. METHODS: A proprietary ELAM instrument holder was attached to both sides of the operating room bed. The device consisted of an articulating arm with custom silicone inserts mounted on a tray (storing up to three endoscopic instruments). ELAM cases were randomized to be performed either with (device) or without the holder (control). Using custom software, instrument pass time (IPT), instrument drop rate (IDR), and communication errors (eg handing incorrect instruments) were manually recorded. Qualitative use metrics relating to overall device satisfaction were also obtained. RESULTS: Data were collected from 25 device and 23 control cases among three different laryngologists. Average IPT was nearly three times quicker for the device (0.80 s, n = 1175 passes) compared with controls (2.09 s, n = 1208 passes) [p < 0.001]. IPT interquartile range was five times higher for control (1.65 s) versus device cases (0.42 s). IDR was not significantly different [p = 0.48]; however, device cases had significantly lower communication errors compared to control cases [p = 0.01]. Surgeons and surgical assistants were similarly satisfied with the device on a 5-point Likert scale (mean: 4.2/5, standard deviation: 0.92). CONCLUSION: The proposed endoscopic instrument holder can improve ELAM operative workflow by reducing instrument passing time and variability without increasing IDR. LEVEL OF EVIDENCE: 2 Laryngoscope, 133:3492-3498, 2023.


Assuntos
Laringoscópios , Laringe , Humanos , Instrumentos Cirúrgicos , Endoscopia , Laringe/cirurgia , Salas Cirúrgicas
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