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PURPOSE: To report a single-institutional experience with hypofractionated radiation therapy alone for human papillomavirus (HPV)-positive oropharyngeal cancer. METHODS AND MATERIALS: A total of 101 consecutive patients were treated by radiation therapy alone using a regimen of 66 Gy in 30 fractions (60 patients) or 70 Gy in 33 fractions (41 patients) for newly diagnosed p16-positive squamous cell carcinoma of the oropharynx. Sixty-seven patients (67%) were never smokers. RESULTS: The 3-year actuarial rates of overall survival, local-regional control, and progression-free survival were 94%, 93%, and 89%, respectively. Among never-smokers, the 3-year rates of overall survival and local-regional control were 98% and 100%, respectively. The grade 3+ acute toxicity rate was 21%, with the most commonly observed side effects related to mucositis. CONCLUSION: Hypofractionated radiation alone resulted in excellent outcomes for patients with HPV-positive oropharyngeal cancer. A prospective clinical trial investigating this modality in the setting of de-escalation is currently underway.
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PURPOSE: As society grows in cultural diversity, an increasing proportion of patients are expected to be from non-English speaking backgrounds. This study sought to compare the clinical outcomes between non-English speakers and English speakers treated by radiation therapy for head and neck cancer. METHODS AND MATERIALS: Seventy-five non-English speaking patients with squamous cell carcinoma of the head and neck were matched to English-speaking controls based on patient and disease variables; clinical outcomes were compared. RESULTS: Non-English speaking patients had inferior 3-year overall survival (64% vs. 77%, p = 0.02) and progression-free survival (59% vs. 73%, p = 0.01) compared with the English-speaking cohort. On logistical regression, non-English-speaking status was associated with a significantly increased risk of overall death (OR = 1.41; 95% CI, 1.09-1.92). CONCLUSIONS: Prognosis differed significantly between non-English speaking and English-speaking patients. Culturally tailored programs to address language barriers should be considered to ameliorate disparities in outcome.
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INTRODUCTION: Despite decades of research on risk-communication approaches, questions remain about the optimal methods for conveying risks for different outcomes across multiple time points, which can be necessary in applications such as discrete choice experiments (DCEs). We sought to compare the effects of 3 design factors: 1) separated versus integrated presentations of the risks for different outcomes, 2) use or omission of icon arrays, and 3) vertical versus horizontal orientation of the time dimension. METHODS: We conducted a randomized study among a demographically diverse sample of 2,242 US adults recruited from an online panel (mean age 59.8 y, s = 10.4 y; 21.9% African American) that compared risk-communication approaches that varied in the 3 factors noted above. The primary outcome was the number of correct responses to 12 multiple-choice questions asking survey respondents to identify specific numbers, contrast options to recognize dominance (larger v. smaller risks), and compute differences. We used linear regression to test the effects of the 3 design factors, controlling for health literacy, graph literacy, and numeracy. We also measured choice consistency in a subsequent DCE choice module. RESULTS: Mean comprehension varied significantly across versions (P < 0.001), with higher comprehension in the 3 versions that provided separated risk information for each risk. In the multivariable regression, separated risk presentation was associated with 0.58 more correct responses (P < 0.001; 95% confidence interval: 0.39, 0.77) compared with integrated risk information. Neither providing icon arrays nor using vertical versus horizontal time formats affected comprehension rates, although participant understanding did correlate with DCE choice consistency. CONCLUSIONS: In presentations of multiple risks over multiple time points, presenting risk information separately for each health outcome appears to increase understanding. HIGHLIGHTS: When conveying information about risks of different outcomes at multiple time points, separate presentations of single-outcome risks resulted in higher comprehension than presentations that combined risk information for different outcomes.We also observed benefits of presenting single-outcome risks separately among respondents with lower numeracy and graph literacy.Study participants who scored higher on risk understanding were more internally consistent in their responses to a discrete choice experiment.
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The emergence of treatment de-escalation as a feasible option for patients with newly diagnosed human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma has generated considerable excitement among both providers and patients alike. Since HPV-positive oropharyngeal carcinoma has been shown to be a unique entity with distinct clinical and molecular characteristics, the rationale for customizing treatment for patients with this disease is compelling. Indeed, evidence has accumulated demonstrating that patients with HPV-positive oropharyngeal cancer have a significantly improved prognosis as a result of their exquisite radiosensitivity compared to their HPV-negative counterparts and thus might possibly be targeted with de-escalated approaches. The fundamental goal of de-escalation is to maintain the high cure and survival rates associated with traditional approaches while reducing the intensity of treatment and thus the incidence of both short- and long-term toxicity. Given the rapidly increasing incidence of this disease, particularly among younger patients who are generally healthy, the focus on quality of life seems germane. Although the exact reason for the improved sensitivity of HPV-positive oropharyngeal carcinoma to treatment is uncertain, prospective studies have now been published demonstrating that de-escalated radiation can successfully maintain the high rates of cure and preserve quality of life for appropriately selected patients with this disease. However, these studies have been fairly heterogeneous in design, and it remains questionable how to apply their findings to real-world practice. The potential of integrating translational approaches into clinical paradigms is also just starting to become recognized. Consequently, multiple uncertainties continue to exist with respect to de-escalation for HPV-positive oropharyngeal cancer, and these questions comprise the crux of this review.
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The nucleus is highly organized, such that factors involved in the transcription and processing of distinct classes of RNA are confined within specific nuclear bodies1,2. One example is the nuclear speckle, which is defined by high concentrations of protein and noncoding RNA regulators of pre-mRNA splicing3. What functional role, if any, speckles might play in the process of mRNA splicing is unclear4,5. Here we show that genes localized near nuclear speckles display higher spliceosome concentrations, increased spliceosome binding to their pre-mRNAs and higher co-transcriptional splicing levels than genes that are located farther from nuclear speckles. Gene organization around nuclear speckles is dynamic between cell types, and changes in speckle proximity lead to differences in splicing efficiency. Finally, directed recruitment of a pre-mRNA to nuclear speckles is sufficient to increase mRNA splicing levels. Together, our results integrate the long-standing observations of nuclear speckles with the biochemistry of mRNA splicing and demonstrate a crucial role for dynamic three-dimensional spatial organization of genomic DNA in driving spliceosome concentrations and controlling the efficiency of mRNA splicing.
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Genoma , Salpicos Nucleares , Precursores de RNA , Splicing de RNA , RNA Mensageiro , Spliceossomos , Animais , Humanos , Masculino , Camundongos , Genes , Genoma/genética , Células-Tronco Embrionárias Humanas/metabolismo , Células-Tronco Embrionárias Murinas/metabolismo , Salpicos Nucleares/genética , Salpicos Nucleares/metabolismo , Precursores de RNA/metabolismo , Precursores de RNA/genética , Splicing de RNA/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Spliceossomos/metabolismo , Transcrição GênicaRESUMO
The capacity for bacterial extracellular electron transfer via secreted metabolites is widespread in natural, clinical, and industrial environments. Recently, we discovered the biological oxidation of phenazine-1-carboxylic acid (PCA), the first example of biological regeneration of a naturally produced extracellular electron shuttle. However, it remained unclear how PCA oxidation was catalyzed. Here, we report the mechanism, which we uncovered by genetically perturbing the branched electron transport chain (ETC) of the soil isolate Citrobacter portucalensis MBL. Biological PCA oxidation is coupled to anaerobic respiration with nitrate, fumarate, dimethyl sulfoxide, or trimethylamine-N-oxide as terminal electron acceptors. Genetically inactivating the catalytic subunits for all redundant complexes for a given terminal electron acceptor abolishes PCA oxidation. In the absence of quinones, PCA can still donate electrons to certain terminal reductases, albeit much less efficiently. In C. portucalensis MBL, PCA oxidation is largely driven by flux through the ETC, which suggests a generalizable mechanism that may be employed by any anaerobically respiring bacterium with an accessible cytoplasmic membrane. This model is supported by analogous genetic experiments during nitrate respiration by Pseudomonas aeruginosa.
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Oxirredução , Fenazinas , Microbiologia do Solo , Fenazinas/metabolismo , Transporte de Elétrons/genética , Citrobacter/genética , Citrobacter/metabolismo , Anaerobiose/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genéticaRESUMO
Interest in the use of de-escalated radiation to treat patients with newly diagnosed human papillomavirus (HPV)-positive oropharyngeal cancer has grown dramatically with the publication of prospective trials demonstrating the efficacy of such an approach. While the rationale for de-escalation--- namely to decrease treatment-related toxicity while maintaining the excellent rates of disease control historically observed in patients with this disease-is inherently obvious, uncertainty exists regarding how to best select patients for de-escalation. Consequently, risk-adapted strategies using a variety of translational and clinical platforms have been increasingly popularized to better refine treatment. These have integrated contemporary methods of mid-treatment response assessment using advanced technologies and molecular assays to customize the radiation dose. By monitoring the response as patients actively proceed through treatment, risk-adapted protocols have the potential to provide insight into the biological behavior of tumors and make individualized therapy possible. The purpose of this review is to summarize the evidence to date on risk-adapted approaches to de-escalated radiation-- highlighting the clinical, radiological, and biological data which may ultimately help usher the principles of precision medicine into practice for patients with HPV-positive oropharyngeal cancer.
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Neoplasias Orofaríngeas , Humanos , Neoplasias Orofaríngeas/radioterapia , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/radioterapia , Infecções por Papillomavirus/complicações , Papillomavirus HumanoRESUMO
Fanconi-Bickel syndrome (FBS) is a rare metabolic disorder caused by decreased glucose transporter 2 (GLUT2) function due to several known mutations in the SLC2A2 gene. As of 2020, 144 cases of FBS have been described in the literature. Metabolic and somatic sequelae include dysglycemia and accumulation of glycogen in the kidney and liver. However, there are no descriptions in the literature of possible neuropsychiatric manifestations of FBS. This case report is to our knowledge the first in this regard, describing a patient with FBS who was admitted to our psychiatric inpatient unit while experiencing acute mania. We conceptualize the case as a novel psychiatric presentation of acute mania in FBS, which may inform our understanding of bipolar disorder pathophysiology because of the hypothesized functional changes in neural pathways involving the paraventricular thalamus induced by decreased GLUT2 activity in FBS.
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Introduction: Interstitial lung disease (ILD) is the most frequent cause of drug-related mortality from EGFR tyrosine kinase inhibitors (TKIs). Yet, for patients with symptomatic osimertinib-induced ILD, the risk of recurrent ILD associated with EGFR TKI rechallenge, either with osimertinib or another TKI, such as erlotinib, is unclear. Methods: Retrospective study of 913 patients who received osimertinib treatment for EGFR mutation-positive NSCLC. Clinical characteristics, ILD treatment history, and subsequent anticancer therapy of patients with symptomatic osimertinib-induced ILD were collated. The primary end point was to compare the incidence of recurrent ILD with osimertinib versus erlotinib rechallenge. Results: Of 913 patients, 35 (3.8%) had symptomatic osimertinib-induced ILD, of which 12 (34%), 15 (43%), and eight (23%) had grade 2, 3 to 4, and 5 ILD, respectively. On ILD recovery, 17 patients had EGFR TKI rechallenge with eight received osimertinib and nine received erlotinib. The risk of recurrent ILD was higher with osimertinib rechallenge than erlotinib (p = 0.0498). Of eight, five (63%) developed recurrent ILD on osimertinib rechallenge, including three patients with fatal outcomes. In contrast, only one of nine patients (11%) treated with erlotinib had recurrent ILD. Median time to second ILD occurrence was 4.7 (range 0.7-12) weeks. Median time-to-treatment failure of patients with erlotinib rechallenge was 13.2 months (95% confidence interval: 8.6-15.0). Conclusions: The risk of recurrent ILD was considerably higher with osimertinib rechallenge than erlotinib. Osimertinib rechallenge should be avoided, whereas erlotinib may be considered in patients with symptomatic osimertinib-induced ILD.
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PURPOSE: The optimal management of local-regionally recurrent head and neck cancer that is not amenable to surgical resection is uncertain. We sought to compare outcomes among patients treated with and without re-irradiation in this setting. METHODS AND MATERIALS: A review of institutional registries identified 65 patients with local-regionally recurrent squamous cell carcinoma of the head and neck who were ineligible for surgery. Forty patients (62 %) opted for re-irradiation with the remaining 25 patients (38 %) undergoing initial systemic therapy alone. All patients had measurable disease. Forty-three patients (66 %) were male and twenty-two (33 %) were female. The median age at the time of recurrence was 59 years (range, 39-84 years). The most common primary sites of disease were the oropharynx, (n = 25), oral cavity (N = 19), and nasopharynx (n = 11). The median interval from completion of prior radiation to the diagnosis of recurrent disease was 35 months (range, 2-102 months). RESULTS: Re-irradiation improved 2-year overall survival, (32 % versus 11 %), progression-free survival (31 % versus 7 %), and local-regional control (39 % versus 3 %) compared to systemic therapy alone (p < 0.05, for both). The likelihood of developing any new grade 3+ toxicity was significantly higher among patients treated by re-irradiation compared to those treated by systemic therapy (53 % vs. 28 %, p < 0.001). There were 3 treatment-related fatalities, all of which occurred in the re-irradiation group. The incidence of grade 3+ late toxicity was 48 % and 12 % for patients in the re-irradiation and systemic therapy cohorts, respectively (p < 0.001). CONCLUSION: Although re-irradiation improved overall survival compared to systemic therapy for appropriately selected patients with local-regionally recurrent head and neck cancer, the relatively high risk of toxicity must be considered.
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Neoplasias de Cabeça e Pescoço , Recidiva Local de Neoplasia , Reirradiação , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Recidiva Local de Neoplasia/radioterapia , Adulto , Idoso de 80 Anos ou mais , Reirradiação/efeitos adversos , Reirradiação/métodos , Neoplasias de Cabeça e Pescoço/radioterapia , Neoplasias de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Estudos RetrospectivosRESUMO
BACKGROUND AND AIMS: Small bowel gastrointestinal bleeding (GIB) is associated with multiple blood transfusions, prolonged and/or multiple hospital admissions, utilization of significant healthcare resources, and negative effects on patient quality of life. There is a well-recognized association between antithrombotic medications and small bowel GIB. We aimed to identify the diagnostic yield of small bowel capsule endoscopy (SBCE) in patients on antithrombotic medications and the impact of SBCE on treatment course. METHODS: The electronic medical records of nineteen hundred eighty-six patients undergoing SBCE were retrospectively reviewed. RESULTS: The diagnostic yield for detecting stigmata of recent bleeding and/or actively bleeding lesions in SBCE was higher in patients that were on antiplatelet agents (21.6%), patients on anticoagulation (22.5%), and in patients that had their SBCE performed while they were inpatient (21.8%), when compared to the patients not on antiplatelet agents (12.1%), patients not on anticoagulation (13.5%), and with patients that had their SBCE performed in the outpatient setting (12%). Of 318 patients who had stigmata of recent bleeding and/or actively bleeding lesion(s) identified on SBCE, SBCE findings prompted endoscopic evaluation (small bowel enteroscopy, esophagogastroduodenoscopy (EGD), and/or colonoscopy) in 25.2%, with endoscopic hemostasis attempted in 52.5%. CONCLUSIONS: Our study, the largest conducted to date, emphasizes the importance of performing SBCE as part of the evaluation for suspected small bowel bleeding, particularly in patients taking antithrombotic therapy, and especially during their inpatient hospital stay.
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Endoscopia por Cápsula , Fibrinolíticos , Hemorragia Gastrointestinal , Intestino Delgado , Humanos , Endoscopia por Cápsula/métodos , Masculino , Feminino , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Intestino Delgado/patologia , Intestino Delgado/diagnóstico por imagem , Fibrinolíticos/efeitos adversos , Fibrinolíticos/uso terapêutico , Inibidores da Agregação Plaquetária/efeitos adversos , Anticoagulantes/efeitos adversos , Idoso de 80 Anos ou maisRESUMO
Purpose: Stereotactic radiosurgery (SRS) for brain metastases is frequently prescribed to the maximum tolerated dose to minimize the probability of local progression. However, many patients die from extracranial disease prior to local progression and may not require maximally aggressive treatment. Recently, improvements in models of SRS tumor control probability (TCP) and overall survival (OS) have been made. We predicted that by combining models of OS and TCP, we could better predict the true risk of local progression after SRS than by using TCP modeling alone. Methods and Materials: Records of patients undergoing SRS at a single institution were reviewed retrospectively. Using established TCP and OS models, for each patient, the probability of 1-year survival [p(OS)] was calculated, as was the probability of 1-year local progression [p(LP)]) for each treated lesion. Joint-probability was used to combine the models [p(LP,OS)=p(LP)*p(OS)]. Analyses were conducted at the individual metastasis and whole-patient levels. Fine-Gray regression was used to model p(LP) or p(LP,OS) on the risk of local progression after SRS, with death as a competing risk. Results: At the patient level, 1-year local progression was 0.08 (95% CI, 0.03-0.15), median p(LP,OS) was 0.13 (95% CI, 0.07-0.2), and median p(LP) was 0.29 (95% CI, 0.22-0.38). At the metastasis level, 1-year local progression was 0.02 (95% CI, 0.01-0.04), median p(LP,OS) was 0.05 (95% CI, 0.02-0.07), and median p(LP) was 0.10 (95% CI, 0.07-0.13). p(LP,OS) was found to be significantly associated with the risk of local progression at the patient level (P = .048) and metastasis level (P = .007); however, p(LP) was not (P = .16 and P = .28, respectively). Conclusions: Simultaneous modeling of OS and TCP more accurately predicted local progression than TCP modeling alone. Better understanding which patients with brain metastases are at risk of local progression after SRS may help personalize treatment to minimize risk without sacrificing efficacy.
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OBJECTIVES: Immunotherapy with immune checkpoint inhibitors has shown only limited success in the management of metastatic soft tissue sarcoma. Overall response rates (ORR) with single agent pembrolizumab were 18% and median PFS was 18 weeks on the clinical trial SARC028. One strategy to improve the responses to immunotherapy is with stereotactic body radiation therapy (SBRT), which can enhance the antitumor CD8 T cell response through the release of tumor-specific antigens, potentially priming a more diverse class of T cell receptors. METHODS: This is a phase 0, pilot prospective study taking place at a single center with 2 arms. In Arm A, patients are treated with pembrolizumab 400 mg IV infusion on day 1 of a 42-day cycle. Stereotactic body radiation therapy (SBRT) is delivered in 1-5 fractions starting on C1D15-28 and given every other day. In Arm B, patients who have started an immune checkpoint inhibitor within 60 days are treated with SBRT in addition to the current therapy. RESULTS: In this study we outline testing the feasibility of adding SBRT to pembrolizumab. CONCLUSION: The ultimate goal of combination therapy is improved overall response, including tumors not treated with SBRT. This trial can be found registered online: NCT05488366.
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Anticorpos Monoclonais Humanizados , Segunda Neoplasia Primária , Radiocirurgia , Sarcoma , Humanos , Inibidores de Checkpoint Imunológico , Projetos Piloto , Estudos Prospectivos , Sarcoma/tratamento farmacológico , Sarcoma/radioterapiaRESUMO
Background: Although electronic prescription cancellation such as via CancelRx can facilitate critical communication between prescribers and pharmacy staff about discontinued medications, there is little work that explores whether CancelRx meets the needs of pharmacy staff users. Objective: This study leverages qualitative interviews with pharmacy staff to address the following question: When medication changes are made by a prescriber using CancelRx, what information is needed by pharmacy staff to make correct and effective decisions in their roles in medication management? Methods: We conducted an inductive thematic analysis of interviews with 11 pharmacy staff members (pharmacists and pharmacy technicians) across three outpatient community pharmacy sites within an academic health care system. Results: Three information needs themes were consistently identified by both pharmacists and pharmacy technicians: prescriber intent when initiating the CancelRx, clinical rationale for the medication change, and intended medication regimen. Notably, both pharmacists and pharmacy technicians often reported seeking multiple information needs not fully addressed by CancelRx in the electronic health record (EHR) to achieve the shared goals of correct dispensing of medications and supporting patient self-management. Conclusions: Our qualitative analysis reveals that outpatient community pharmacy staff in an academic health care system often seek additional information from the (EHR) following medication changes communicated by CancelRx to meet their information needs. Ideally, the prescriber would provide sufficient information through CancelRx to automatically identify all discontinued prescriptions. These limitations highlight the need for design features that support routine communication of needed information at the time of a medication change, such as structured data elements.
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Purpose: For patients without pathologic evidence of cervical disease after neck dissection for cutaneous squamous cell carcinoma involving the parotid region, inclusion of the ipsilateral cervical neck in the postparotidectomy radiation volume is routinely performed. We report our experience with selective avoidance of the ipsilateral neck for patients undergoing postoperative radiation to the parotid bed. Methods and Materials: From January 2014 to December 2023, a total of 30 consecutive patients underwent postoperative radiation after parotidectomy for cutaneous squamous cell carcinoma involving the parotid area. All patients had previously had a neck dissection confirming pathologic N0 disease. Treatment was delivered using intensity modulated radiation therapy to a median dose of 60 Gy (range, 56-66 Gy). The radiation target volumes included the parotid bed only, with deliberate avoidance of the ipsilateral cervical neck. The median pathologic tumor size of the parotid tumor was 3.3 cm (range, 0.2-9.4 cm). Final pathologic evaluation showed positive microscopic margins in 8 patients (27%), perineural invasion in 17 patients (57%), and facial nerve involvement in 6 patients (20%). Results: There were no isolated nodal failures. One patient developed an ipsilateral neck recurrence approximately 8 months after completion of radiation therapy. This occurred 2 months subsequent to the development of local recurrence. The 5-year actuarial rates of local (parotid) control, neck control, and overall survival were 87%, 97%, and 76%, respectively. Conclusions: Omission of the ipsilateral neck from the parotid volume does not compromise disease control for pathologically N0 patients undergoing postoperative radiation for cutaneous squamous cell carcinoma involving the parotid region. Practical implications are discussed.
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PURPOSE: The timely delivery of health care is an important quality indicator that has been shown to correlate with outcomes for cancer patients. We present our single-institution experience with the implementation of a same-day-access scheduling initiative in outpatient radiation oncology. METHODS AND MATERIALS: From March 2021 to March 2023, a total of 4301 consecutive new patients referred for radiation oncology consultation were offered same-day appointments as part of a prospective pilot initiative conducted at a tertiary-based academic medical center. Descriptive statistics were used to study the effect of this initiative on access-related benchmarks compared with historical control patients referred during a preceding 24-month period. RESULTS: Among the 3414 patients scheduled, 477 (14%) opted for same-day appointments. Black, Latino, and Asian patients were significantly more likely to use same-day access versus Caucasian patients (P < .001). The same-day-access initiative increased the proportion of patients seen within 5 days from referral from 22% to 61% (P < .001). The median time from referral to consult was 12 days (range, 0-149 days) before the implementation of the same-day-access initiative compared with 3 days (range, 0-101 days) after (P < .001). The no-show rate was reduced from 15% to 7% with the initiative (P < .001). All patients who requested a same-day appointment were successfully accommodated. CONCLUSIONS: The implementation of this same-day-access initiative enhanced operational efficiency and reduced barriers to care in the outpatient setting.
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Neoplasias , Radioterapia (Especialidade) , Humanos , Benchmarking , Estudos Prospectivos , Agendamento de Consultas , Neoplasias/radioterapiaRESUMO
BACKGROUND: Vertebral body tethering and other non-fusion techniques for the treatment of pediatric idiopathic scoliosis are increasing in popularity. There is limited physician consensus on this topic as the result of a paucity of published data regarding which patients most benefit from non-fusion strategies. Thus, much of the decision-making is left to patients and parents, who must select a treatment based on their goals and values and the information available from health-care providers, the internet, and social media. We sought to understand patient and family preferences regarding the attributes of fusion versus non-fusion surgery that drive these choices. METHODS: Patients and families were recruited from 7 pediatric spine centers and were asked to complete a survey-based choice experiment that had been jointly developed with the U.S. Food and Drug Administration (FDA) to evaluate patient preferences. Choices between experimentally designed alternatives were analyzed to estimate the relative importance of outcomes and requirements associated with the choice options (attributes). The attributes included appearance, confidence in the planned correction, spinal motion, device failure, reoperation, and recovery period. The inclusion criteria were (1) an age of 10 to 21 years and (2) a diagnosis of adolescent idiopathic scoliosis in patients who were considering, or who had already undergone, treatment with fusion or non-fusion surgery. Preference weights were estimated from the expected changes in choice given changes in the attributes. RESULTS: A total of 344 respondents (124 patients, 92 parents, and 128 parent/patient dyads) completed the survey. One hundred and seventy-three patients were enrolled prior to surgery, and 171 were enrolled after surgery. Appearance and motion were found to be the most important drivers of choice. For the entire cohort, fusion was preferred over non-fusion. For patients who were considering surgery, the most important attributes were preservation of spinal motion and appearance. CONCLUSIONS: Patients and families seeking treatment for idiopathic scoliosis value appearance and preservation of spinal motion and, to a lesser extent, reoperation rates when considering fusion versus non-fusion surgery.
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Escoliose , Fusão Vertebral , Adolescente , Humanos , Criança , Adulto Jovem , Adulto , Escoliose/cirurgia , Coluna Vertebral , Pais , Preferência do Paciente , Consenso , Fusão Vertebral/métodos , Resultado do TratamentoRESUMO
Carboxysomes are protein microcompartments that function in the bacterial CO2 concentrating mechanism (CCM) to facilitate CO2 assimilation. To do so, carboxysomes assemble from thousands of constituent proteins into an icosahedral shell, which encapsulates the enzymes Rubisco and carbonic anhydrase to form structures typically > 100 nm and > 300 megadaltons. Although many of the protein interactions driving the assembly process have been determined, it remains unknown how size and composition are precisely controlled. Here, we show that the size of α-carboxysomes is controlled by the disordered scaffolding protein CsoS2. CsoS2 contains two classes of related peptide repeats that bind to the shell in a distinct fashion, and our data indicate that size is controlled by the relative number of these interactions. We propose an energetic and structural model wherein the two repeat classes bind at the junction of shell hexamers but differ in their preferences for the shell contact angles, and thus the local curvature. In total, this model suggests that a set of specific and repeated interactions between CsoS2 and shell proteins collectively achieve the large size and monodispersity of α-carboxysomes.
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Proteínas de Bactérias , Anidrases Carbônicas , Proteínas de Bactérias/química , Dióxido de Carbono/metabolismo , Ribulose-Bifosfato Carboxilase/metabolismo , Peptídeos/metabolismo , Anidrases Carbônicas/metabolismo , Organelas/metabolismoRESUMO
Objective: World Trade Center (WTC) responders are susceptible to both cognitive and neuropsychiatric impairments, particularly chronic posttraumatic stress disorder. The present study examined self-reported behavioral impairments in a sample of 732 WTC responders, 199 of whom were determined to have high risk of WTC-related cortical atrophy by an artificial neural network. Results: We found that responders at increased risk of cortical atrophy showed behavioral impairment across five domains: motivation, mood, disinhibition, empathy, and psychosis (14.6% vs 3.9% in the low-risk group; P = 3.90 × 10-7). Factor analysis models revealed that responders at high risk of cortical atrophy tended to have deficits generalized across all aspects of behavioral impairment with focal dysfunction in sensory psychosis. We additionally describe how relationships are modulated by exposure severity and pharmacological treatments. Discussion: Our findings suggest a potential link between sensory deficits and the development of cortical atrophy in WTC responders and may indicate symptoms consistent with a clinical portrait of parietal dominant Alzheimer's disease or a related dementia (ADRD). Results underscore the importance of investigating neuropsychiatric symptomatology in clinical evaluations of possible ADRD.