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Receptor tyrosine kinases such as EGF receptor (EGFR) stimulate phosphoinositide 3 kinases to convert phosphatidylinositol-4,5-bisphosophate [PtdIns(4,5)P2] into phosphatidylinositol-3,4,5-trisphosphate [PtdIns(3,4,5)P3]. PtdIns(3,4,5)P3 then remodels actin and gene expression, and boosts cell survival and proliferation. PtdIns(3,4,5)P3 partly achieves these functions by triggering activation of the kinase Akt, which phosphorylates targets like Tsc2 and GSK3ß. Consequently, unchecked upregulation of PtdIns(3,4,5)P3-Akt signaling promotes tumor progression. Interestingly, 50-70% of PtdIns and PtdInsPs have stearate and arachidonate at sn-1 and sn-2 positions of glycerol, respectively, forming a species known as 38:4-PtdIns/PtdInsPs. LCLAT1 and MBOAT7 acyltransferases partly enrich PtdIns in this acyl format. We previously showed that disruption of LCLAT1 lowered PtdIns(4,5)P2 levels and perturbed endocytosis and endocytic trafficking. However, the role of LCLAT1 in receptor tyrosine kinase and PtdIns(3,4,5)P3 signaling was not explored. Here, we show that LCLAT1 silencing in MDA-MB-231 and ARPE-19 cells abated the levels of PtdIns(3,4,5)P3 in response to EGF signaling. Importantly, LCLAT1-silenced cells were also impaired for EGF-driven and insulin-driven Akt activation and downstream signaling. Thus, our work provides first evidence that the LCLAT1 acyltransferase is required for receptor tyrosine kinase signaling.
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Aciltransferasas , Factor de Crecimiento Epidérmico , Receptores ErbB , Fosfatos de Fosfatidilinositol , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatos de Fosfatidilinositol/metabolismo , Factor de Crecimiento Epidérmico/metabolismo , Factor de Crecimiento Epidérmico/farmacología , Aciltransferasas/metabolismo , Receptores ErbB/metabolismo , Línea Celular Tumoral , Fosforilación , Proliferación CelularRESUMEN
INTRODUCTION: Maxillary reconstruction is a complex undertaking characterized by a 3-dimensional surgical site with deficiencies in multiple tissue types. Prior to virtual surgical planning(VSP), bony reconstruction was inaccurate and inefficient, thus reconstructions defaulted to soft tissue flaps or obturators. The current study describes an efficient and accurate approach to bony maxillary reconstruction with immediate dental implant placement(IDIP). METHODS: A reconstructive workflow was developed for osseous reconstruction to improve functional and aesthetic outcomes. Critical aspects include VSP, 3-D printed plates and IDIP. Review of a prospectively maintained database identified patients who underwent osseous maxillary reconstruction with a fibula flap and immediate dental implants from 2017-2022, with a focus on oncologic characteristics and reconstructive outcomes. RESULTS: During the study, 20 patients underwent maxillary reconstruction with VSP and IDIP. One dental implant out of 55 failed to osseointegrate and no flaps were lost. Three patients suffered partial loss of the fibula skin island; one required palatal closure with a radial forearm flap, and two were managed with outpatient debridement. Fifteen patients achieved either an interim or final retained dental prosthesis. All prostheses achieved acceptable aesthetic results without the instability associated with non-bone borne devices(e.g.dentures/obturators). No patients experienced delays in oncologic treatment. CONCLUSIONS: VSP technology has enabled surgeons to replace like with like to achieve better outcomes with acceptable morbidity for maxillary defects. IDIP provides all patients an opportunity for a fixed prosthesis even though not all complete the process. This maxillary reconstruction workflow can be safely accomplished in oncologic patients with promising and effective early results.
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BACKGROUND: Most males with cystic fibrosis (MwCF) have congenital bilateral absence of the vas deferens and require assisted reproductive technology to conceive, yet many have limited knowledge about how CF affects sexual and reproductive health (SRH). This study evaluates the feasibility, acceptability, and potential effectiveness of telehealth fertility preservation (FP) counseling for MwCF. METHODS: Pre-lung transplant MwCF ≥18 years, recruited from U.S. CF centers, social media, and via snowball sampling, received individualized telehealth counseling. Participants completed intervention feasibility/acceptability one week post-counseling and FP knowledge, care satisfaction, and self-efficacy assessments at baseline and two months post-counseling. We completed acceptability interviews one-week post-counseling and audio-recorded, transcribed, and thematically analyzed results. We descriptively analyzed survey results and conducted pre/post comparisons using paired t-tests. RESULTS: Thirty MwCF (ages 22-49 years) completed counseling. Most were in a relationship (70 %) and White (86.7 %). Telehealth FP counseling was acceptable (M = 4.38/5 ± 0.60), appropriate (M = 4.37/5 ± 0.60), and feasible (M = 4.60/5 ± 0.45) to MwCF. FP knowledge (9.53 vs. 10.40/12; p = .010), care satisfaction (20.23 vs 26.67/32; p<.001), and self-efficacy (22.87 vs 25.20/30; p = .016) improved at two months post-counseling. Despite desiring provider-initiated SRH, wanting children (81 %), and perceiving the CF team as their primary care provider (97 %), 44 % report not receiving information about infertility by the CF team. CONCLUSIONS: Integrating FP counseling into CF care is feasible and acceptable to MwCF and can improve FP knowledge, self-efficacy, and care satisfaction. MwCF desire early and regular provider-initiated SRH education.
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Consejo , Fibrosis Quística , Preservación de la Fertilidad , Telemedicina , Humanos , Fibrosis Quística/terapia , Fibrosis Quística/psicología , Masculino , Adulto , Consejo/métodos , Preservación de la Fertilidad/métodos , Persona de Mediana Edad , Estudios de Factibilidad , Estados Unidos , Infertilidad Masculina/etiología , Infertilidad Masculina/prevención & control , Infertilidad Masculina/terapia , Infertilidad Masculina/psicología , Aceptación de la Atención de Salud/psicología , Aceptación de la Atención de Salud/estadística & datos numéricosRESUMEN
Importance: Rates of physician-diagnosed eczema have been increasing among older adults, but little is known regarding the pathophysiologic processes and best treatments in this subgroup. Preliminary data suggest that medications-antihypertensive medications in particular-may contribute to eczematous dermatitis; however, there are limited population-based data on the proportion of eczematous dermatitis diagnoses among older adults that may be attributed to antihypertensive drugs. Objectives: To determine whether antihypertensive drug use is associated with eczematous dermatitis in older adults. Design, Settings, and Participants: This was a longitudinal cohort study of a population-based sample of individuals 60 years and older without a diagnosis of eczematous dermatitis at baseline. It was conducted at primary care practices participating in The Health Improvement Network in the United Kingdom from January 1, 1994, to January 1, 2015. Data analyses were performed from January 6, 2020, to February 6, 2024. Exposure: Exposure date by first prescription for an antihypertensive drug within each drug class. Main outcome measures: Newly active eczematous dermatitis was based on the first date for 1 of the 5 most common eczema codes used in a previously validated algorithm. Results: Among the total study sample of 1â¯561â¯358 older adults (mean [SD] age, 67 [9] years; 54% female), the overall prevalence of eczematous dermatitis was 6.7% during a median (IQR) follow-up duration of 6 (3-11) years. Eczematous dermatitis incidence was higher among participants receiving antihypertensive drugs than those who did not (12 vs 9 of 1000 person-years of follow-up). Adjusted Cox proportional hazard models found that participants who received any antihypertensive drugs had a 29% increased hazard rate of any eczematous dermatitis (hazard ratio [HR], 1.29; 95% CI, 1.26-1.31). When assessing each antihypertensive drug class individually, the largest effect size was observed for diuretic drugs (HR, 1.21; 95% CI, 1.19-1.24) and calcium channel blockers (HR, 1.16; 95% CI, 1.14-1.18), and the smallest effect sizes were for angiotensin-converting enzyme inhibitors (HR, 1.02; 95% CI, 1.00-1.04) and ß-blockers (HR, 1.04; 95% CI, 1.02-1.06). Conclusions and Relevance: This cohort study found that antihypertensive drugs were associated with a small increased rate of eczematous dermatitis, with effect sizes largest for calcium channel blockers and diuretic drugs, and smallest for angiotensin-converting enzyme inhibitors and ß-blockers. Although additional research is needed to understand the mechanisms underlying the association, these data could be helpful to clinicians to guide management when a patient presents with eczematous dermatitis in older age.
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Antihipertensivos , Eccema , Humanos , Femenino , Masculino , Anciano , Antihipertensivos/efectos adversos , Antihipertensivos/administración & dosificación , Eccema/tratamiento farmacológico , Estudios Longitudinales , Persona de Mediana Edad , Reino Unido , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiología , Anciano de 80 o más Años , Erupciones por Medicamentos/etiología , Erupciones por Medicamentos/epidemiología , Estudios de CohortesRESUMEN
There is a marked disparity in the state of knowledge of Holartic x Neotropical species of the freshwater snail family Physidae; the incipiency of data on Neotropical physids reflecting the lower number of dedicated specialists. The gaps in the knowledge on Neotropical physids have led to historical uncertainty about species validity. Revisiting the species is essential to reduce taxonomic impediment and delineating their probable distribution is the first step to attain this purpose. We aimed at critically analyze occurrence records of South American physids, compiled through an intensive search in the literature, biodiversity and molecular databases. We present a provisional characterization of the distribution of this family in South America, considering the probable versus the poorly documented distribution of the species. The critical underrepresentation of South American physids in collections, molecular databases and literature reinforces the role of taxonomic impediment in delaying the advance of the knowledge on species diversity. Malacological collections represented the main source of records, evidencing the relevance of unpublished data associated to specimens to assess distributional information on neglected groups. As most of the species are represented by shells, the reassessment of species identity and distribution must be done, using molecular and anatomical criteria for species delimitation.
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Biodiversidad , Animales , América del Sur , Distribución Animal , Gastrópodos/clasificación , Caracoles/clasificaciónRESUMEN
Hygge practices embody joy, peace, mindfulness, coziness, and conviviality. Cystic fibrosis (CF) is a progressive condition with complex therapies and physical limitations. Little is known about how hygge practice may impact individuals living with CF. A qualitative study explored how adults with CF use hygge practices to promote wellness and cope with their disease. A purposive network sample of 15 adults with CF who utilized hygge practices completed semistructured audio-recorded telephone interviews. Recordings were transcribed and analyzed using Colaizzi's thematic analysis approach. Results reveal that hygge practices influenced individuals' aesthetics, attitudes, and activities, deeply impacting the physical and emotional experience of living with CF. Incorporating hygge into CF care may improve psychological well-being and quality of life for members of this community.
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Fibrosis Quística , Adulto , Humanos , Fibrosis Quística/psicología , Calidad de Vida/psicología , Emociones , Investigación CualitativaRESUMEN
Obesity is a pandemic that disproportionately affects children from vulnerable populations in the USA. Current treatment approaches in primary care settings in the USA have been reported to be insufficient at managing pediatric obesity, primarily due to implementation challenges for healthcare systems and barriers for families. While the literature has examined the efficacy of pediatric obesity interventions focused on internal validity, it lacks sufficient reporting and analysis of external validity necessary for successful translation to primary care settings. We conducted a systematic review of the primary-care-setting literature from January 2007 to March 2020 on family-based pediatric weight management interventions in both English and/or Spanish for children ages 6-12 years in the USA using the Reach, Efficacy/Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework. A literature search, using PRISMA guidelines, was conducted in January 2022 using the following electronic databases: Medline Ovid, Embase, and Cochrane Library. 22 270 records were screened, and 376 articles were reviewed in full. 184 studies were included. The most commonly reported dimensions of the RE-AIM framework were Reach (65%), Efficacy/Effectiveness (64%), and Adoption (64%), while Implementation (47%) and Maintenance (42%) were less often reported. The prevalence of reporting RE-AIM construct indicators ranged greatly, from 1% to 100%. This systematic review underscores the need for more focus on external validity to guide the development, implementation, and dissemination of future pediatric obesity interventions based in primary care settings. It also suggests conducting additional research on sustainable financing for pediatric obesity interventions.
Pediatric weight management research focused on primary care centers for children ages 612 in the USA has typically focused on assessing the effectiveness of the intervention rather than how to translate and disseminate such interventions into different settings for diverse populations, or external validity. Using the Reach, Efficacy/Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework, we conducted a systematic review to report how existing research reports external validity.
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Promoción de la Salud , Obesidad Infantil , Niño , Humanos , Promoción de la Salud/métodos , Obesidad Infantil/prevención & control , Atención Primaria de SaludRESUMEN
Autophagy is a major catabolic degradation and recycling process that maintains homeostasis in cells and is especially important in postmitotic neurons. We implemented a high-content phenotypic assay to discover small molecules that promote autophagic flux and completed target identification and validation studies to identify protein targets that modulate the autophagy pathway and promote neuronal health and survival. Efficient syntheses of the prioritized compounds were developed to readily access analogues of the initial hits, enabling initial structure-activity relationship studies to improve potency and preparation of a biotin-tagged pulldown probe that retains activity. This probe facilitated target identification and validation studies through pulldown and competition experiments using both an unbiased proteomics approach and western blotting to reveal Lamin A/C and LAMP1 as the protein targets of compound RH1115. Evaluation of RH1115 in neurons revealed that this compound induces changes to LAMP1 vesicle properties and alters lysosome positioning. Dysfunction of the autophagy-lysosome pathway has been implicated in a variety of neurodegenerative diseases, including Alzheimer's disease, highlighting the value of new strategies for therapeutic modulation and the importance of small-molecule probes to facilitate the study of autophagy regulation in cultured neurons and in vivo.
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Enfermedad de Alzheimer , Lamina Tipo A , Humanos , Lamina Tipo A/metabolismo , Autofagia/fisiología , Neuronas/metabolismo , Lisosomas/metabolismo , Enfermedad de Alzheimer/metabolismo , Proteína 1 de la Membrana Asociada a los Lisosomas/metabolismoRESUMEN
PURPOSE: The primary aim of this study was the examination of relationships between students' preadmission achievement, intraphysician assistant (PA) program achievement, and Physician Assistant National Certifying Examination (PANCE) performance using path analysis regression. Second, this study explored the extent to which the theoretical model differed based on several key demographic variables: sex and undergraduate major. METHODS: This retrospective, single-institution study examined data from 2015 to 2022 (n = 322). Analysis included descriptive statistics, bivariate correlations, and path analysis using structural equation modeling to examine direct, indirect, and total effects of all predictors on the primary outcome variable, PANCE. RESULTS: PACKRAT-I demonstrated the largest total effect size on PANCE total score (ß = .45). Total effect size on PANCE was small yet significant for prerequisite grade point average (GPA), Graduate Record Exam verbal and quantitative subscores, a comprehensive didactic cardiology examination, didactic and clinical year GPAs, and End of Rotation examination mean score (ß < .25). The relationship between mean preceptor evaluation score and PANCE was nonsignificant. Subgroup analyses showed differences between female and male in the relationship between several didactic variables and preceptor evaluations. No differences were detected between groups based on undergraduate major. CONCLUSION: This PANCE analysis revealed relationships among pre-PA and intra-PA performance metrics that may subsequently support data-informed strategies for programs to identify at-risk students, aid student success, and support the assessment of curriculum. Future studies should replicate the approach using a larger, multi-institution sample that examines additional preprogram and intraprogram achievement variables.
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Background: Cystic fibrosis (CF) is a rare genetic disease affecting approximately 30,000 people in the United States (US). African American persons with CF are even rarer, comprising approximately 5% of this population. Purpose: The purpose of this study was to explore the lived experiences of African American persons with CF to identify potential disparities in health care. Methods: Descriptive phenomenology was used to explore lived experiences of African American persons with CF over age 18 recruited from CF Foundation-accredited Centers in the US, CF-specific social media, and via snowball sampling. Study data was obtained through telephone interviews that were audio-recorded, transcribed verbatim, and analyzed using Colaizzi's method of thematic analysis. Results: Six men and six women (ages 23-45) completed the study. Interviews revealed three themes: (1) Accepting a Diagnosis of CF; (2) Desiring a Normal Life while Living with an Invisible Disease; and 3) A Slippery Slope of Subtle Racism. Each theme had 2-3 subthemes. Conclusions: It is critical to explore the unique challenges faced by African American persons with CF in order to develop interventions that improve their daily lives and create better futures. Implications for Practice: Findings highlight the unique challenges faced by underrepresented groups with CF and the need to address health inequities to improve care delivery.
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Fibrosis Quística , Racismo , Femenino , Humanos , Masculino , Negro o Afroamericano , Atención a la Salud , Investigación Cualitativa , Estados Unidos , Adulto Joven , Adulto , Persona de Mediana EdadRESUMEN
We report an interesting case of pericardial effusion associated with idiopathic systemic capillary leak syndrome (ISCLS) following administration of SARS-CoV-2 vaccine. This patient initially presented with dyspnoea and chest pain, with non-pitting oedema and clear lung fields. The diagnosis of ISCLS was made based on the clinical syndrome and laboratory evidence of polycythaemia and hypoalbuminaemia. An enlarging pericardial effusion was diagnosed on transthoracic echocardiogram. Daily point-of-care ultrasound (POCUS)-guided volume management and serial transthoracic echocardiograms contributed to avoidance of refractory shock, cardiac tamponade and critical care admission.
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Vacunas contra la COVID-19 , Síndrome de Fuga Capilar , Derrame Pericárdico , Humanos , Síndrome de Fuga Capilar/inducido químicamente , Síndrome de Fuga Capilar/complicaciones , Taponamiento Cardíaco , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Derrame Pericárdico/inducido químicamente , Derrame Pericárdico/complicacionesRESUMEN
Background: The role of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) neutralizing antibody response from natural infection and vaccination, and the potential determinants of this response are poorly understood. Characterizing this antibody response and the factors associated with neutralization can help inform future prevention efforts and improve clinical outcomes in those infected. Objectives: The goals of this study were to prospectively evaluate SARS-CoV-2 antibody levels and the neutralizing antibody responses among naturally infected adults and to determine demographic and behavioral factors independently associated with these responses. Methods: Serum was collected from seropositive individuals at baseline, four-weeks, and three-months following their first study visit to be evaluated for antibody levels. Detection of neutralizing antibodies was performed at baseline. Participant demographic and behavioral information was collected via web questionnaire prior to their first visit. Results: At baseline, higher antibody levels were associated with better neutralization capacity, with 83% of participants having detectable neutralizing antibodies. We found an age-dependent effect on antibody level and neutralization capacity with participants over 65 years having significantly higher levels. Ethnicity, heart disease, autoimmune disease, and COVID symptoms were associated with higher antibody levels, but not with increased neutralization capacity. Work environment during the pandemic correlated with increased neutralization capacity, while kidney or liver disease and traveling out of state after February 2020 correlated with decreased neutralization capacity, however neither correlated with antibody levels. Conclusions: Our data show that natural infection by SARS-CoV-2 can induce a humoral response reflected by high antibody levels and neutralization capacity.
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Adolescent idiopathic scoliosis (AIS) is the most common form of scoliosis. Treatment depends on the degree of curvature, skeletal maturity, and age of the patient. Once the curve reaches 50 degrees, posterior spinal fusion (PSF) is necessary to stabilize the spine and prevent further progression of the curve. PSF causes significant trauma to the tissues and often results in significant pain postoperatively. The purpose of this article is to provide the audience with a review of preoperative, intraoperative, and postoperative pain control with an accelerated protocol in patients with AIS undergoing PSF.
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Escoliosis , Fusión Vertebral , Humanos , Adolescente , Escoliosis/cirugía , Columna VertebralRESUMEN
High-grade serous ovarian cancer (HGSOC) is the most common and lethal ovarian cancer histotype. Lack of early detection methods, limited therapeutic agents, and low 5-year survival rate reflect the urgent need to develop new therapies. Eupenifeldin, a bistropolone, originally isolated from Eupenicillium brefeldianum, is a cytotoxic fungal metabolite. In three HSGOC cell lines (OVCAR3, OVCAR5, OVCAR8), eupenifeldin was found to have an IC50 value less than 10 nM, while 10 times higher concentrations were required for cytotoxicity in nontumorigenic fallopian tube secretory epithelial cell lines (FTSEC). An in vivo hollow fiber assay showed significant cytotoxicity in OVCAR3. Eupenifeldin significantly increased Annexin V staining in OVCAR3 and -8, but not OVCAR5. Eupenifeldin activated caspases 3/7 in OVCAR3, OVCAR5, and OVCAR8; however, cleaved PARP was only detected in OVCAR3. Quantitative proteomics performed on OVCAR3 implicated ferroptosis as the most enriched cell death pathway. However, validation experiments did not support ferroptosis as part of the cytotoxic mechanism of eupenifeldin. Autophagic flux and LC3B puncta assays found that eupenifeldin displayed weak autophagic induction in OVCAR3. Inhibition of autophagy by cotreatment with bafilomycin reduced the toxicity of eupenifeldin, supporting the idea that induction of autophagy contributes to the cytotoxic mechanism of eupenifeldin.
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Antineoplásicos , Neoplasias Ováricas , Humanos , Femenino , Neoplasias Ováricas/tratamiento farmacológico , Apoptosis , Línea Celular TumoralRESUMEN
Acute myeloid leukemias (AMLs) frequently harbor activating mutations in Fms-like tyrosine kinase 3 (FLT3). The use of FLT3 inhibitors (FLT3i) is the standard of care for treatment of newly diagnosed and relapsed patients with AML. Differentiation responses including clinical differentiation syndrome have been previously reported with FLT3i when used as single agents in relapsed disease. We present a case of hypereosinophilia in a patient on FLT3i therapy with persistent FLT3 polymerase chain reaction (PCR) positivity in peripheral blood. We sorted mature leukocytes by lineage to determine if the eosinophils were leukemia-derived. FLT3 PCR and next-generation sequencing analysis demonstrated monocytic differentiation of the FLT3-ITD leukemic clone with reactive hypereosinophilia that was derived from a preleukemic SF3B1, FLT3 wild-type clone. Our case is the first to definitively demonstrate the emergence of clonal FLT3-ITD monocytes with FLT3i and the first to demonstrate a differentiation response following decitabine, venetoclax, and gilteritinib triplet therapy.
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Eosinofilia , Leucemia Mieloide Aguda , Humanos , Tirosina Quinasa 3 Similar a fms/genética , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Compuestos de AnilinaRESUMEN
OBJECTIVE: To evaluate the effect of risk-reducing salpingo-oophorectomy (RRSO) on change in bone mineral density (BMD) in women aged 34-50 years with pathogenic variants in BRCA1 or BRCA2 ( BRCA1 /2). METHODS: The PROSper (Prospective Research of Outcomes after Salpingo-oophorectomy) study is a prospective cohort of women aged 34-50 years with BRCA1 or two germline pathogenic variants that compares health outcomes after RRSO to a non-RRSO control group with ovarian conservation. Women aged 34-50 years, who were planning either RRSO or ovarian conservation, were enrolled for 3 years of follow-up. Spine and total hip BMD were measured by dual-energy X-ray absorptiometry (DXA) scans obtained at baseline before RRSO or at the time of enrollment for the non-RRSO group, and then at 1 and 3 years of study follow-up. Differences in BMD between the RRSO and non-RRSO groups, as well as the association between hormone use and BMD, were determined by using mixed effects multivariable linear regression models. RESULTS: Of 100 PROSper participants, 91 obtained DXA scans (RRSO group: 40; non-RRSO group: 51). Overall, total spine, and hip BMD decreased significantly from baseline to 12 months after RRSO (estimated percent change -3.78%, 95% CI -6.13% to -1.43% for total spine; -2.96%, 95% CI -4.79% to -1.14% for total hip) and at 36 months (estimated percent change -5.71%, 95% CI -8.64% to -2.77% for total spine; -5.19%, 95% CI -7.50% to -2.87% for total hip. In contrast, total spine and hip BMD were not significantly different from baseline for the non-RRSO group. The differences in mean percent change in BMD from baseline between the RRSO and non-RRSO groups were statistically significant at both 12 and 36 months for spine BMD (12-month difference -4.49%, 95% CI -7.67% to -1.31%; 36-month difference -7.06%, 95% CI -11.01% to -3.11%) and at 36 months for total hip BMD (12-month difference -1.83%, 95% CI -4.23% to 0.56%; 36-month difference -5.14%, 95% CI -8.11% to -2.16%). Across the study periods, hormone use was associated with significantly less bone loss at both the spine and hip within the RRSO group compared with no hormone use ( P <.001 at both 12 months and 36 months) but did not completely prevent bone loss (estimated percent change from baseline at 36 months -2.79%, 95% CI -5.08% to -0.51% for total spine BMD; -3.93%, 95% CI -7.27% to -0.59% for total hip BMD). CONCLUSION: Women with pathogenic variants in BRCA1 /2 who undergo RRSO before the age of 50 years have greater bone loss after surgery that is clinically significant when compared with those who retain their ovaries. Hormone use mitigates, but does not eliminate, bone loss after RRSO. These results suggest that women who undergo RRSO may benefit from routine screening for BMD changes to identify opportunities for prevention and treatment of bone loss. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT01948609.
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Neoplasias de la Mama , Neoplasias Ováricas , Femenino , Humanos , Densidad Ósea , Proteína BRCA1 , Proteína BRCA2 , Genes BRCA1 , Genes BRCA2 , Mutación , Neoplasias Ováricas/genética , Neoplasias Ováricas/prevención & control , Ovariectomía/métodos , Estudios Prospectivos , Salpingooforectomía/métodos , Adulto , Persona de Mediana EdadRESUMEN
PURPOSE: This retrospective cohort study compared postoperative as-needed (PRN) opioid consumption pre and postimplementation of a perioperative multimodal analgesic injection composed of ropivacaine, epinephrine, ketorolac, and morphine in patients undergoing posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS). Secondary outcomes include pain score measurements, time to ambulation, length of stay, blood loss, 90-day complication rate, operating room time, nonopioid medication usage, and total inpatient medication cost before and after the initiation of this practice. METHODS: Consecutive patients weighing ≥ 20 kg who underwent PSF for a primary diagnosis of AIS between January 2017 and December 2020 were included. Data from 2018 were excluded to account for standardization of the practice. Patients treated in 2017 only received PCA. Patients treated in 2019 and 2020 only received the injection. Excluded were patients who had any diagnoses other than AIS, allergies to any of the experimental medications, or who were nonambulatory. Data were analyzed utilizing the two-sample t-test or Chi-squared test as appropriate. RESULTS: Results of this study show that compared with 47 patients treated postoperatively with patient-controlled analgesia (PCA), 55 patients treated with a multimodal perioperative injection have significantly less consumption of PRN morphine equivalents (0.3 mEq/kg vs. 0.5 mEq/kg; p = 0.02). Furthermore, patients treated with a perioperative injection have significantly higher rates of ambulation on postoperative day 1 compared with those treated with PCA (70.9 vs. 40.4%; p = 0.0023). CONCLUSION: Administration of a perioperative injection is effective and should be considered in the perioperative protocol in patients undergoing PSF for AIS. LEVEL OF EVIDENCE: Therapeutic Level III.
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Escoliosis , Fusión Vertebral , Humanos , Adolescente , Estudios Retrospectivos , Fusión Vertebral/métodos , Escoliosis/cirugía , Dolor Postoperatorio/tratamiento farmacológico , Analgésicos , MorfinaRESUMEN
OBJECTIVE: This retrospective study explored the impact of time to surgery in acute hip fractures and outcomes in patients with acute hip fractures at a level I trauma center within an academic medical center in the southeastern United States. The objective was to explore the association between time to surgery and 30-day mortality and outcomes in adults 65 years and older undergoing hip fracture surgery for traumatic injuries in 2014-2019. METHODS: The population of this study consisted of patients who presented with a hip fracture and required operative measures. The research team conducted a secondary data analysis of medical records among patients who experienced a hip fracture and subsequent hip surgery to address the injury. RESULTS: Results from this study demonstrated a statistically significant relationship between a delay in surgery and an increase in postoperative complications and morbidity, as well as increased morbidity among male patients. CONCLUSIONS: Incidence of hip fractures is increasing among older adult patients and is cause for concern because of an associated high mortality rate and risk of postoperative complications. The existing body of literature indicates earlier surgical intervention may improve outcomes and reduce postoperative complications and mortality. The results of this study affirm these findings and suggest further examination specifically among males.
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Fracturas de Cadera , Humanos , Masculino , Anciano , Estudios Retrospectivos , Fracturas de Cadera/cirugía , Complicaciones Posoperatorias/epidemiología , Centros Médicos Académicos , Análisis de Datos SecundariosRESUMEN
BACKGROUND: Current predictive models of lymphedema risk cannot predict with 100% certainty which patients will go on to develop lymphedema and which will not. Patient-specific anatomic and physiologic differences may be the missing factor. The authors hypothesize that patients with accessory lymphatic pathways may have improved lymphatic drainage, resulting in smaller limb volumes. METHODS: The authors reviewed indocyanine green (ICG) lymphography images of all patients who presented to their institution for evaluation of breast cancer-related lymphedema. Patients with unilateral upper extremity lymphedema, a full set of bilateral limb measurements, and ICG images of both limbs were included. Other variables of interest included patient demographics and length of follow-up. Patients with accessory pathways were determined independently, and conflicts were resolved with discussion. Abnormal images were also evaluated for common drainage pathways. RESULTS: Thirty patients were identified as having accessory lymphatic drainage pathways. These patients had significantly smaller limb volume differences [8.19% (SD, 11.22)] compared with patients who did not exhibit these pathways [20.74% (SD, 19.76); P < 0.001]. The most common pathway was absence or rerouting of the radial bundle to the ulnar or volar bundles ( n = 16). CONCLUSIONS: The ability to create accessory lymphatic drainage pathways may be associated with improved lymphatic drainage, resulting in smaller limb volumes. Furthermore, certain drainage pathways appear to be more common than others. Description of these pathways should be considered for inclusion in ICG lymphography image grading criteria. Further study is needed to clarify the nature of these pathways and whether these pathways affect subjective symptoms and quality of life. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.