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1.
J Surg Res ; 301: 578-583, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39053172

RESUMO

INTRODUCTION: A growing sector of humanitarian surgical nongovernmental organizations (NGOs) is providing care in low- and middle-income countries. Minimal data exists regarding this extremely heterogeneous community. This study aims to describe the demographics and clinical practices of surgical NGOs. We hypothesize there are identifiable attributes of such organizations which correlate with success. METHODS: A survey was sent to 83 US-based surgical NGOs directly providing general or subspecialty surgical care in low- and middle-income countries. Further information was obtained from organizations' websites. Descriptive statistics were performed to analyze organizational attributes and define protocol-driven practices. RESULTS: Thirty NGOs (36%) responded, averaging 20 ± 11 y of operation. Annually, US humanitarian surgical organizations performed a wide range of operations (10-15,000) with 52% performing fewer than 200 operations per year. Sixty-seven percent of responders were classified as strongly protocol-driven. Only twenty percent reported deviation from standard US practice occurs often or very often, most commonly in pain management (18%), preoperative workup (16%), and operative technique (16%). CONCLUSIONS: To our knowledge, this is the first effort to describe the characteristics and clinical practices of the humanitarian surgical sector. There exists a wide scope of clinical practice among responding surgical NGOs, however mostly consistent with US standards, with a prevalance of protocol-driven clinical approach. Developing consensus-based protocols may help standardize and improve quality of care for surgical NGOs.

2.
Sci Rep ; 14(1): 15296, 2024 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961203

RESUMO

Blast wave exposure, a leading cause of hearing loss and balance dysfunction among military personnel, arises primarily from direct mechanical damage to the mechanosensory hair cells and supporting structures or indirectly through excessive oxidative stress. We previously reported that HK-2, an orally active, multifunctional redox modulator (MFRM), was highly effective in reducing both hearing loss and hair cells loss in rats exposed to a moderate intensity workday noise that likely damages the cochlea primarily from oxidative stress versus direct mechanical trauma. To determine if HK-2 could also protect cochlear and vestibular cells from damage caused primarily from direct blast-induced mechanical trauma versus oxidative stress, we exposed rats to six blasts of 186 dB peak SPL. The rats were divided into four groups: (B) blast alone, (BEP) blast plus earplugs, (BHK-2) blast plus HK-2 and (BEPHK-2) blast plus earplugs plus HK-2. HK-2 was orally administered at 50 mg/kg/d from 7-days before to 30-day after the blast exposure. Cochlear and vestibular tissues were harvested 60-d post-exposure and evaluated for loss of outer hair cells (OHC), inner hair cells (IHC), auditory nerve fibers (ANF), spiral ganglion neurons (SGN) and vestibular hair cells in the saccule, utricle and semicircular canals. In the untreated blast-exposed group (B), massive losses occurred to OHC, IHC, ANF, SGN and only the vestibular hair cells in the striola region of the saccule. In contrast, rats treated with HK-2 (BHK-2) sustained significantly less OHC (67%) and IHC (57%) loss compared to the B group. OHC and IHC losses were smallest in the BEPHK-2 group, but not significantly different from the BEP group indicating lack of protective synergy between EP and HK-2. There was no loss of ANF, SGN or saccular hair cells in the BHK-2, BEP and BEPHK-2 groups. Thus, HK-2 not only significantly reduced OHC and IHC damage, but completely prevented loss of ANF, SGN and saccule hair cells. The powerful protective effects of this oral MFRM make HK-2 an extremely promising candidate for human clinical trials.


Assuntos
Traumatismos por Explosões , Células Ciliadas Vestibulares , Gânglio Espiral da Cóclea , Animais , Gânglio Espiral da Cóclea/efeitos dos fármacos , Gânglio Espiral da Cóclea/patologia , Ratos , Traumatismos por Explosões/prevenção & controle , Células Ciliadas Vestibulares/efeitos dos fármacos , Células Ciliadas Vestibulares/metabolismo , Masculino , Oxirredução , Ratos Sprague-Dawley , Cóclea/efeitos dos fármacos , Cóclea/patologia , Células Ciliadas Auditivas/efeitos dos fármacos , Células Ciliadas Auditivas/patologia , Estresse Oxidativo/efeitos dos fármacos , Perda Auditiva Provocada por Ruído/prevenção & controle , Perda Auditiva Provocada por Ruído/patologia
3.
J Acad Nutr Diet ; 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39025233

RESUMO

BACKGROUND: Various foods and nutrients are linked with higher or lower risk of rheumatoid arthritis (RA), yet these associations are inconsistent across studies. Limited research has been done evaluating the association between diet quality and RA in a larger scale prospective study on postmenopausal women. OBJECTIVE: The objective of this study was to evaluate the association between dietary quality and risk of incident RA in postmenopausal women. DESIGN: This is a prospective cohort study as part of the Women's Health Initiative (WHI) with an average follow-up time of 8.1 years. Baseline diet was measured using a food frequency questionnaire (FFQ). Diet quality was evaluated by the Healthy Eating Index (HEI) - 2015 total score. In addition, intake of food groups/nutrients that align with HEI-2015 components was assessed. PARTICIPANTS/SETTING: 109,591 postmenopausal women were included in this study, which was conducted at various clinical centers across the US with recruitment from 1993 to 1998. WHI participants who were missing outcome data, had unreliable/missing FFQ data, or had RA at baseline were excluded. MAIN OUTCOME MEASURES: The primary outcome measure is incident RA. STATISTICAL ANALYSES PERFORMED: Multivariable Cox proportional regression analysis was performed evaluating the association of diet quality with self-reported physician-diagnosed RA after adjusting for age, race, ethnicity, education status, income, and body mass index (BMI). RESULTS: During 857,517 person-years of follow-up, 5,823 incident RA cases were identified. After adjustment for multiple comparisons, compared to quartile 1, quartiles 2, 3, and 4 of the HEI-2015 total scores were associated with a lower RA risk of 1%, 10%, and 19%, respectively (p-trend < 0.001). Greater consumption of total fruits (p-trend=0.014), whole fruits (p-trend<0.0002), total vegetables (p-trend=0.008), greens and beans (p-trend<0.0002), whole grains (p-trend=0.008), and dairy (p-trend=0.018) were significantly associated with lower rates of incident RA. Conversely, higher consumption of saturated fat (p-trend=0.002) was significantly associated with higher rates of incident RA. CONCLUSION: A higher quality diet reflected by higher HEI-2015 total scores was inversely associated with incident rheumatoid arthritis in post-menopausal women.

6.
Pediatr Blood Cancer ; 71(9): e31172, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38956810

RESUMO

INTRODUCTION: Children with WAGR (Wilms tumor, aniridia, genitourinary anomalies, and range of development delays) syndrome are predisposed to Wilms tumor (WT) and intrinsic kidney disease. Using the comprehensive International WAGR Syndrome Association (IWSA) survey of children with WAGR syndrome, we analyzed tumor characteristics, treatment and congenital risk factors, and kidney function in children with WAGR and WT. METHODS: Descriptive statistics were utilized including demographics, treatment strategies, and patient outcomes. Comparisons were made between patients with WAGR and WT to those with WAGR alone. A multivariable logistic regression was completed for risk of developing WT and to identify predictors of chronic kidney disease (CKD). RESULTS: Sixty-four of 145 children with WAGR developed WT (44.1%). Three relapsed and one died. CKD developed in five children with WAGR without WT (5/81, 6.2%), and in 34 with WAGR and WT (34/64, 28.3%). Children with WAGR and WT were younger (p = .017), and had a greater association with CKD than WAGR children without WT (p < .0001). Two children with WT required hemodialysis, and one underwent kidney transplantation. By univariate analysis, CKD at any stage was associated with complete nephrectomy for the WT surgery (p < .0001), chemotherapy duration greater than 12 months, and three-drug therapy. Upon multivariate analysis, prior nephrectomy was the only significant variable (p = .0002). CONCLUSIONS: Epidemiological analysis of children with WAGR demonstrated favorable oncologic outcomes, but high rate of early CKD in those who developed WT. Further study of the use of nephron-sparing surgery in children with WAGR and strategies to delay or treat early CKD are needed.


Assuntos
Neoplasias Renais , Insuficiência Renal Crônica , Síndrome WAGR , Tumor de Wilms , Humanos , Tumor de Wilms/cirurgia , Tumor de Wilms/patologia , Tumor de Wilms/complicações , Masculino , Feminino , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/patologia , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Síndrome WAGR/patologia , Pré-Escolar , Criança , Lactente , Adolescente , Nefrectomia , Fatores de Risco , Prognóstico , Seguimentos
7.
J Cheminform ; 16(1): 82, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39030583

RESUMO

PURPOSE: Reaction databases are a key resource for a wide variety of applications in computational chemistry and biochemistry, including Computer-aided Synthesis Planning (CASP) and the large-scale analysis of metabolic networks. The full potential of these resources can only be realized if datasets are accurate and complete. Missing co-reactants and co-products, i.e., unbalanced reactions, however, are the rule rather than the exception. The curation and correction of such incomplete entries is thus an urgent need. METHODS: The SynRBL framework addresses this issue with a dual-strategy: a rule-based method for non-carbon compounds, using atomic symbols and counts for prediction, alongside a Maximum Common Subgraph (MCS)-based technique for carbon compounds, aimed at aligning reactants and products to infer missing entities. RESULTS: The rule-based method exceeded 99% accuracy, while MCS-based accuracy varied from 81.19 to 99.33%, depending on reaction properties. Furthermore, an applicability domain and a machine learning scoring function were devised to quantify prediction confidence. The overall efficacy of this framework was delineated through its success rate and accuracy metrics, which spanned from 89.83 to 99.75% and 90.85 to 99.05%, respectively. CONCLUSION: The SynRBL framework offers a novel solution for recalibrating chemical reactions, significantly enhancing reaction completeness. With rigorous validation, it achieved groundbreaking accuracy in reaction rebalancing. This sets the stage for future improvement in particular of atom-atom mapping techniques as well as of downstream tasks such as automated synthesis planning. SCIENTIFIC CONTRIBUTION: SynRBL features a novel computational approach to correcting unbalanced entries in chemical reaction databases. By combining heuristic rules for inferring non-carbon compounds and common subgraph searches to address carbon unbalance, SynRBL successfully addresses most instances of this problem, which affects the majority of data in most large-scale resources. Compared to alternative solutions, SynRBL achieves a dramatic increase in both success rate and accurary, and provides the first freely available open source solution for this problem.

8.
Childs Nerv Syst ; 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39046474

RESUMO

PURPOSE: We demonstrate the complexities of managing pediatric patients on extracorporeal membrane oxygenation (ECMO) therapy requiring neurosurgery, focusing on systemic anticoagulation, cardiac function, and medically refractory intracranial pressure (ICP). METHODS: A 3.5-year-old female with Tetralogy of Fallot developed severe ischemic cerebral edema following post-operative cardiac arrest and required ECMO. This case, along with four additional cases of children requiring neurosurgery while on ECMO, was examined. RESULTS: Emergency neurosurgical intervention in the primary case led to significant improvement, highlighting the delicate balance between managing ECMO-induced anticoagulation and urgent neurosurgical needs. The additional cases had variable outcomes, emphasizing the challenges of caring for these critically ill patients. CONCLUSION: Successful management of children requiring ECMO support and neurosurgical intervention requires thoughtful multidisciplinary care. This report illustrates some of the nuances in such decision-making, and demonstrates one potential path to a good outcome.

9.
JCO Glob Oncol ; 10: e2400171, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38991182

RESUMO

PURPOSE: Prostate cancer has emerged as a significant public health challenge in the Middle East, characterized by rising incidence rates and a concerning mortality-to-incidence ratio. Yet, despite these alarming trends, data regarding prostate cancer awareness in the region remain limited. To address this critical knowledge gap, this study investigates prostate cancer awareness within the Middle East. MATERIALS AND METHODS: A cross-sectional survey was performed among 5,913 men age 40 years and older across 14 Middle Eastern countries between January 1, 2022, and July 31, 2023. Excluding those with a history of prostate cancer, a validated questionnaire assessed prostate cancer awareness. Data were analyzed using frequencies and percentages for categorical variables, medians and ranges for continuous variables, and Pearson chi-square analysis for relationships between education levels and awareness of prostate cancer. RESULTS: The survey achieved a 74.9% response rate, with 4,431 male participants. Regarding prostate cancer awareness, 83.8% of participants had heard of the disease. However, only 31.0% correctly identified it as the most common malignancy in men, and 21.8% believed it affects both sex. Awareness of screening was limited, with just 19.1% recognizing the prostate-specific antigen test's role. Additionally, participants had a pessimistic view, with a mean perception that 75% of patients with prostate cancer die from the disease, rather than from other causes. Higher education levels were associated with significantly increased awareness of prostate cancer (P < .001). CONCLUSION: This study reveals that while general awareness of the disease exists, crucial knowledge deficits regarding risk factors, screening, and prognosis are evident. Addressing these knowledge gaps through culturally tailored education may improve early detection rates, treatment outcomes, and ultimately reduce the burden of prostate cancer in the Middle East.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Neoplasias da Próstata , Humanos , Masculino , Estudos Transversais , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/psicologia , Oriente Médio/epidemiologia , Pessoa de Meia-Idade , Adulto , Inquéritos e Questionários , Idoso , Detecção Precoce de Câncer/psicologia
10.
Artigo em Inglês | MEDLINE | ID: mdl-38997870

RESUMO

It was the aim of the study to analyze the distribution and pattern of facial fractures following e-scooter trauma. Prospective audit data of facial fractures were retrospectively collected to investigate the impact of e-scooter hire, specifically in the form of facial fractures associated with their use. Data collected included patient demographics, mode of injury, date of injury, facial bones involved, presence of soft tissue injury, and factors associated with injury, including intoxication and helmet use. A total of 849 patients were treated for facial fractures during the study period, of which 34 were attributed to e-scooter use. One-half of those injured riding e-scooters were intoxicated, and one-quarter were wearing helmets. There have been an increasing number of facial fractures associated with e-scooter use following the start of the shared e-scooter trial. Zygomaticomaxillary complex fractures were the most common pattern of facial fracture seen. Most patients required surgical management of their injuries. Policymakers should consider how to improve the enforcement of current regulations, given the healthcare cost associated with the management of these preventable injuries.

11.
J Surg Oncol ; 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39004940

RESUMO

BACKGROUND AND METHODS: Although signet ring cell (SRC) histology is associated with resistance to neoadjuvant chemoradiotherapy and worse overall survival (OS) in esophageal adenocarcinoma (EAC), its prognostic relationship among patients who survive the early period following resection is unknown. EAC patients who underwent trimodality therapy at a single institution (2006-2018) were identified. Bayesian multivariable regression (BMR) analyses of OS and additional OS from a 3-year landmark were performed. RESULTS: Of 631 patients, SRCs were present in 16.0% (N = 101). SRC was associated with shorter median OS (45.8 [95% confidence interval: 31.0-96.7] vs. 79.8 [63.0-107.2] months; p = 0.014). In BMR analysis, the absence of an SRC component was moderately associated with improved OS (probability of beneficial effect, PBE = 0.879). Three-year conditional BMR analysis of additional OS (N = 357) showed that SRC status no longer had a prognostic effect (PBE = 0.546); higher pathological stage was strongly associated with worse additional OS (PBE < 0.001). CONCLUSIONS: The presence of SRC portends worse OS following trimodality therapy for EAC. However, this prognostic impact is dynamic and abates by 3 years postoperatively. In contrast, a higher pathological stage is strongly associated with poor overall and 3-year conditional survival. DISCUSSION: These findings may inform postoperative patient counseling and surveillance protocols.

12.
Nature ; 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39020166

RESUMO

The tumour evolution model posits that malignant transformation is preceded by randomly distributed driver mutations in cancer genes, which cause clonal expansions in phenotypically normal tissues. Although clonal expansions can remodel entire tissues1-3, the mechanisms that result in only a small number of clones transforming into malignant tumours remain unknown. Here we develop an in vivo single-cell CRISPR strategy to systematically investigate tissue-wide clonal dynamics of the 150 most frequently mutated squamous cell carcinoma genes. We couple ultrasound-guided in utero lentiviral microinjections, single-cell RNA sequencing and guide capture to longitudinally monitor clonal expansions and document their underlying gene programmes at single-cell transcriptomic resolution. We uncover a tumour necrosis factor (TNF) signalling module, which is dependent on TNF receptor 1 and involving macrophages, that acts as a generalizable driver of clonal expansions in epithelial tissues. Conversely, during tumorigenesis, the TNF signalling module is downregulated. Instead, we identify a subpopulation of invasive cancer cells that switch to an autocrine TNF gene programme associated with epithelial-mesenchymal transition. Finally, we provide in vivo evidence that the autocrine TNF gene programme is sufficient to mediate invasive properties and show that the TNF signature correlates with shorter overall survival of patients with squamous cell carcinoma. Collectively, our study demonstrates the power of applying in vivo single-cell CRISPR screening to mammalian tissues, unveils distinct TNF programmes in tumour evolution and highlights the importance of understanding the relationship between clonal expansions in epithelia and tumorigenesis.

13.
Circulation ; 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39051104

RESUMO

BACKGROUND: Whether vigorous exercise increases risk of ventricular arrhythmias for individuals diagnosed and treated for congenital long-QT syndrome (LQTS) remains unknown. METHODS: The National Institutes of Health-funded LIVE-LQTS study (Lifestyle and Exercise in Genetic Cardiovascular Conditions) prospectively enrolled individuals 8 to 60 years of age with phenotypic or genotypic LQTS from 37 sites in 5 countries from May 2015 to February 2019. Participants (or parents) answered physical activity and clinical events surveys every 6 months for 3 years with follow-up completed in February 2022. Vigorous exercise was defined as ≥6 metabolic equivalents for >60 hours per year. A blinded Clinical Events Committee adjudicated the composite end point of sudden death, sudden cardiac arrest, ventricular arrhythmia treated by an implantable cardioverter defibrillator, and likely arrhythmic syncope. A National Death Index search ascertained vital status for those with incomplete follow-up. A noninferiority hypothesis (boundary of 1.5) between vigorous exercisers and others was tested with multivariable Cox regression analysis. RESULTS: Among the 1413 participants (13% <18 years of age, 35% 18-25 years of age, 67% female, 25% with implantable cardioverter defibrillators, 90% genotype positive, and 49% with LQT1), 91% were treated with beta-blockers, left cardiac sympathetic denervation, or implantable cardioverter defibrillator; 52% participated in vigorous exercise (55% competitively). Thirty-seven individuals experienced the composite end point (including one sudden cardiac arrest and one sudden death in the nonvigorous group, one sudden cardiac arrest in the vigorous group) with overall event rates at 3 years of 2.6% in the vigorous and 2.7% in the nonvigorous exercise groups. The unadjusted hazard ratio for experience of events for the vigorous group compared with the nonvigorous group was 0.97 (90% CI, 0.57-1.67), with an adjusted hazard ratio of 1.17 (90% CI, 0.67-2.04). The upper 95% one-sided confidence level extended beyond the 1.5 boundary. Neither vigorous or nonvigorous exercise was found to be superior in any group or subgroup. CONCLUSIONS: Among individuals diagnosed with phenotypic or genotypic LQTS who were risk assessed and treated in experienced centers, LQTS-associated cardiac event rates were low and similar between those exercising vigorously and those not exercising vigorously. Consistent with the low event rate, CIs are wide, and noninferiority was not demonstrated. These data further inform shared decision-making discussions between patient and physician about exercise and competitive sports participation. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02549664.

14.
J Arthroplasty ; 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39047922

RESUMO

BACKGROUND: Depression is associated with inferior outcomes following hip or knee arthroplasty, though it remains unclear if this relationship is modifiable. This study examined the association between pharmacologic treatment of depression and patient-reported outcomes. METHODS: This retrospective cohort study of 1,651 total hip arthroplasty (THA) and 1,792 total knee arthroplasty (TKA) procedures between October 2012 and June 2019 used institutional registry data linked to nationwide pharmaceutical claims. The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) global score, with pain and function sub-scales assessed as secondary outcomes. The TKA and THA patients were analyzed separately via mixed-effect linear regression to compare patients who had depression treated with antidepressants (TKA, n = 210; THA, n = 150) to those who had untreated depression (TKA, n = 43; THA; n = 50), and those who did not have depression (TKA, n = 1,539; THA, n = 1,451). RESULTS: Among patients who had depression, not receiving preoperative antidepressant therapy was associated with smaller improvements in WOMAC global scores (TKA, adjusted mean difference [MD]: -13.1 points, 95% CI [confidence interval]: -21.4 to -4.8; THA, MD: -8.5 points, 95% CI: -15.7 to -1.2) at two years after surgery, but not at one year (TKA, MD: -5.4 points, 95% CI: -12.9 to 2.1; THA, MD: -6.3 points, 95% CI: -12.9 to 0.3). Those who did not have depression had similar improvements in WOMAC global scores to those who had treated depression at both one (TKA, MD: 0.8 points, 95% CI: -2.7 to 4.4; THA, MD: 1.8 points, 95% CI: -1.8 to 5.4) and two years (TKA, MD: -1.1 points, 95% CI: -4.9 to 2.7; THA, MD: -1.6 points, 95% CI: -5.6 to 2.3). The findings were consistent with secondary outcomes. CONCLUSION: Among patients who have depression, antidepressant therapy before TKA or THA is associated with improved outcomes. Additional studies are needed to establish the impact of interventions to address untreated depression before surgery.

15.
J Gen Intern Med ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38981941

RESUMO

BACKGROUND: Screening for health-related social needs (HRSN) has become more widespread but the best method of delivering the screening tool is not yet known. OBJECTIVE: Describe HRSN screening completion rate, specifically portal-based and in-person tablet-based screening. DESIGN: Cross-sectional retrospective observational study. PARTICIPANTS: Adults age 18 or older who had a non-acute primary care visit at one of three internal medicine primary care clinics at a large, urban, academic medical center between July 2022 and July 2023. MAIN MEASURES: We identified the proportion of individuals who were screened using the HRSN questionnaire, whether screening was completed by patient-portal or tablet, as well as the degree of burden of HRSN. Using the electronic health record, we explored associations between sociodemographic characteristics and HRSN attributes. KEY RESULTS: Our study included 24,597 patients, of whom 37% completed the HRSN questionnaire. A smaller proportion of Black/African American patients and those with Medicaid insurance completed the questionnaire, yet they comprised a greater percentage of those who screened positive for unmet HRSN (p ≤ 0.001). Most patients completed the questionnaire by patient-portal (86.1%) compared with in-office tablets (14.0%). A larger proportion of those who completed screening by tablet screened positive for HRSN. Of all patients screened, 21.8% were positive for an unmet HRSN and 11.5% had more than one unmet HRSN. CONCLUSIONS: A majority of patients are not being screened for HRSN and results illustrate disparities when screening patients for HRSN through portal-based compared with supplemental in-office tablet-based screening. Prevalence of unmet HRSN varied by demographics such as race and insurance status.

16.
Int J Cancer ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38973574

RESUMO

The objective of this study is to report the long-term timing and patterns of relapse for children enrolled in Children's Oncology Group AREN0534, a multicenter phase III clinical trial conducted from 2009 to 2015. Participants included children with bilateral Wilms tumor (BWT) or unilateral WT with genetic predisposition to develop BWT followed for up to 10 years. Smoothed hazard (risk) functions for event-free survival (EFS) were plotted so that the timing of events could be visualized, both overall and within pre-specified groups. Two hundred and twenty-two children (190 BWT and 32 unilateral WT with BWT predisposition) were followed for a median of 8.6 years. Fifty events were reported, of which 48 were relapse/progression. The overall 8-year EFS was 75% (95% confidence interval: 69%-83%). The highest risk for an EFS event was immediately after diagnosis with a declining rate over 2 years. A second peak of events was observed around 4 years after diagnosis, and a small number of events were reported until the end of the follow-up period. In subset analyses, later increases in risk were more commonly observed in patients with female sex, anaplastic histology, negative lymph nodes or margins, and favorable histology Wilms tumor patients with post-chemotherapy intermediate risk. Among relapses that occurred after 2 years, most were to the kidney. These patterns suggest that late events may be second primary tumors occurring more commonly in females, although more investigation is required. Clinicians may consider observation of patients with BWT beyond 4 years from diagnosis.

17.
Med Phys ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38980082

RESUMO

BACKGROUND: The proximity of the rectum to the prostate in radiation therapy (RT) for prostate cancer presents a significant dosimetric challenge, leading to high rectal doses and resulting in detrimental side effects. Perirectal tissue spacing reduces rectal dose and gastrointestinal toxicities by mechanically separating these organs. A variety of materials have been explored for use as rectal spacers, most recently, a stabilized hyaluronic acid (HA) gel, which can be formed into deliberate a shape, and retains the definition of that shape, while remaining flexible, unlike polyethylene glycol (PEG) hydrogels. PURPOSE: This study evaluates the dosimetric impact of the spacer, including shape symmetry, the degree of separation at different locations, and the temporal stability of the space. Our goal is to provide physics-informed guidance on the optimal use of this sculptable spacer. METHODS: A secondary analysis was performed on data from a 13-center prospective randomized trial (NCT04189913), involving 136 patients with centrally-reviewed treatment plans conducted on CT/MR simulation scans before and after receiving HA spacer implants. Patients were treated with 60 Gy in 20 fractions to the prostate. For this study, python software was utilized for automated processing of DICOM RTstruct and RTdose files, facilitating detailed analysis of the spacer's impact on anatomical displacement and dosimetric outcomes. Complete dose-volume histograms (DVHs) were reconstructed, and combined into composite population DVHs before and after implant, verified against trial-reported dose points. Patients were divided into similar groups of separation and symmetry, and differences in their composite DVHs were tested for significance. Stability of the spacer was studied by comparing serial MRI images and by computing the distance between contours at four axial planes, at simulation and 3-month follow-up, post RT. RESULTS: The introduction of the HA spacer significantly enhanced rectal sparing, as evidenced by a reduction in the mean rectal integral dose by over 6 Gy. High rates of implant symmetry (>95%) were observed, indicating nearly optimal lateral spacer placement. In superior-inferior coverage, this study like many others, saw the spacing largest at the superior extent but becoming more variable inferiorly at the level of the prostate apex. This allowed study of the apex as a specific area for dosimetric concern. Stability assessments confirmed that the spacer maintained its position and dimensions between the simulation and the 3-month post-RT, implying stable geometry during treatment, with only minimal separation changes observed. Statistical analysis using the Kruskal-Wallis test revealed significant correlations of larger separations at the inferior and apical planes with improved dosimetric outcomes, including rV30Gy. CONCLUSION: The use of a stabilized HA spacer in prostate RT effectively enhances prostate-rectum separation, leading to significant rectal sparing without undesirable dose compromises. This study underscores the role of strategic placement and shape, specifically including > 1 cm separation from the base down to the prostate apex. When combined with the treatment planning techniques used in the trial to create a steep dosimetric gradient across the spacer, these findings elucidate the dosimetric outcomes that can be expected in the clinical implementation of HA spacer. This is particularly relevant in the evolution of hypofractionated treatment regimens for prostate cancer therapy.

18.
Digit J Ophthalmol ; 30(2): 22-26, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962668

RESUMO

Purpose: To describe the Versatile Teaching Eye (VT Eye), a 3D-printed model eye designed to provide an affordable examination simulator, and to report the results of a pilot program introducing the VT Eye and an ophthalmic training curriculum at a teaching hospital in Ghana. Methods: TinkerCAD was used to design the VT Eye, which was printed with ABS plastic. The design features an adapter that permits use of a smartphone as a digital fundus. We developed a set of digital flashcards allowing for an interactive review of a range of retinal pathologies. An analog fundus was developed for practicing traditional slit lamp and indirect examinations as well as retinal laser practice. The model was used for a period of 2 weeks by ophthalmic trainees at Komfo Anokye Teaching Hospital, Kumasi, Ghana, to practice indirect ophthalmoscopy, slit lamp biomicroscopy, smartphone funduscopy, and retinal image drawing. Results were assessed at by means of a pre-/post-training survey of 6 residents. Results: The VT Eye accommodates diverse fundus examination techniques. Its 3D-printed design ensures cost-effective, high-quality replication. When paired with a 20 D practice examination lens, the digital fundus provides a comprehensive, interactive training environment for <$30.00 (USD). This device allows for indirect examination practice without requiring an indirect headset, which may increase the amount of available practice for trainees early in their careers. In the Ghana pilot program, the model's use in indirect examination training sessions significantly boosted residents' confidence in various examination techniques. Comparing pre- and post-session ratings, average reported confidence levels rose by 30% for acquiring clear views of the posterior pole, 42% for visualizing the periphery, and 141% for capturing important pathology using personal smartphones combined with a 20 D lens (all P < 0.05). Conclusions: The VT Eye is readily reproducible and can be easily integrated into ophthalmic training curricula, even in regions with limited resources. It offers an effective and affordable training solution, underscoring its potential for global adoption and the benefits of incorporating innovative technologies in medical education.


Assuntos
Modelos Anatômicos , Oftalmologia , Impressão Tridimensional , Humanos , Oftalmologia/educação , Gana , Projetos Piloto , Oftalmoscopia/métodos , Internato e Residência , Currículo , Educação de Pós-Graduação em Medicina/métodos
19.
Sci Rep ; 14(1): 15145, 2024 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956134

RESUMO

Hepatitis C virus (HCV) is a plus-stranded RNA virus that often chronically infects liver hepatocytes and causes liver cirrhosis and cancer. These viruses replicate their genomes employing error-prone replicases. Thereby, they routinely generate a large 'cloud' of RNA genomes (quasispecies) which-by trial and error-comprehensively explore the sequence space available for functional RNA genomes that maintain the ability for efficient replication and immune escape. In this context, it is important to identify which RNA secondary structures in the sequence space of the HCV genome are conserved, likely due to functional requirements. Here, we provide the first genome-wide multiple sequence alignment (MSA) with the prediction of RNA secondary structures throughout all representative full-length HCV genomes. We selected 57 representative genomes by clustering all complete HCV genomes from the BV-BRC database based on k-mer distributions and dimension reduction and adding RefSeq sequences. We include annotations of previously recognized features for easy comparison to other studies. Our results indicate that mainly the core coding region, the C-terminal NS5A region, and the NS5B region contain secondary structure elements that are conserved beyond coding sequence requirements, indicating functionality on the RNA level. In contrast, the genome regions in between contain less highly conserved structures. The results provide a complete description of all conserved RNA secondary structures and make clear that functionally important RNA secondary structures are present in certain HCV genome regions but are largely absent from other regions. Full-genome alignments of all branches of Hepacivirus C are provided in the supplement.


Assuntos
Sequência Conservada , Genoma Viral , Hepacivirus , Conformação de Ácido Nucleico , RNA Viral , Hepacivirus/genética , RNA Viral/genética , RNA Viral/química , Humanos , Alinhamento de Sequência , Hepatite C/virologia , Hepatite C/genética
20.
Behav Res Methods ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38829553

RESUMO

This tutorial is designed for speech scientists familiar with the R programming language who wish to construct experiment interfaces in R. We begin by discussing some of the benefits of building experiment interfaces in R-including R's existing tools for speech data analysis, platform independence, suitability for web-based testing, and the fact that R is open source. We explain basic concepts of reactive programming in R, and we apply these principles by detailing the development of two sample experiments. The first of these experiments comprises a speech production task in which participants are asked to read words with different emotions. The second sample experiment involves a speech perception task, in which participants listen to recorded speech and identify the emotion the talker expressed with forced-choice questions and confidence ratings. Throughout this tutorial, we introduce the new R package speechcollectr, which provides functions uniquely suited to web-based speech data collection. The package streamlines the code required for speech experiments by providing functions for common tasks like documenting participant consent, collecting participant demographic information, recording audio, checking the adequacy of a participant's microphone or headphones, and presenting audio stimuli. Finally, we describe some of the difficulties of remote speech data collection, along with the solutions we have incorporated into speechcollectr to meet these challenges.

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