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1.
Nat Commun ; 15(1): 6059, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39025847

RESUMO

Synthetic lethality provides an attractive strategy for developing targeted cancer therapies. For example, cancer cells with high levels of microsatellite instability (MSI-H) are dependent on the Werner (WRN) helicase for survival. However, the mechanisms that regulate WRN spatiotemporal dynamics remain poorly understood. Here, we used single-molecule tracking (SMT) in combination with a WRN inhibitor to examine WRN dynamics within the nuclei of living cancer cells. WRN inhibition traps the helicase on chromatin, requiring p97/VCP for extraction and proteasomal degradation in a MSI-H dependent manner. Using a phenotypic screen, we identify the PIAS4-RNF4 axis as the pathway responsible for WRN degradation. Finally, we show that co-inhibition of WRN and SUMOylation has an additive toxic effect in MSI-H cells and confirm the in vivo activity of WRN inhibition using an MSI-H mouse xenograft model. This work elucidates a regulatory mechanism for WRN that may facilitate identification of new therapeutic modalities, and highlights the use of SMT as a tool for drug discovery and mechanism-of-action studies.


Assuntos
Cromatina , Proteínas Inibidoras de STAT Ativados , Proteína com Valosina , Helicase da Síndrome de Werner , Helicase da Síndrome de Werner/metabolismo , Helicase da Síndrome de Werner/genética , Humanos , Animais , Cromatina/metabolismo , Proteína com Valosina/metabolismo , Proteína com Valosina/genética , Proteínas Inibidoras de STAT Ativados/metabolismo , Proteínas Inibidoras de STAT Ativados/genética , Camundongos , Linhagem Celular Tumoral , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Instabilidade de Microssatélites , Proteólise/efeitos dos fármacos , Sumoilação/efeitos dos fármacos , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Feminino
3.
Neuropsychopharmacology ; 49(2): 414-421, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37524753

RESUMO

The hormonal changes of pregnancy and parturition can trigger robust changes in affective state, particularly among patients with a history of postpartum depression. However, more work is needed to elucidate the temporal dynamics of symptom emergence. The current study explored how quickly hormone-sensitive (HS+) individuals can be differentiated from hormone-insensitive (HS-) controls in the context of a tightly controlled experimental hormone manipulation, and which symptoms demonstrate the most rapid, consistent, and largest response during this protocol. Participants were female, non-pregnant, and euthymic, with a history of DSM-5 major depressive episode with peripartum onset (n = 15) or parous healthy controls with no psychiatric history (n = 15). Perinatal hormonal changes were simulated by inducing hypogonadism, adding back estradiol (E2) and progesterone (P4) to reach first-trimester levels for 8 weeks, and then subsequently withdrawing both hormones. Those reporting a 30% or greater increase during addback or withdrawal on select subscales of the Inventory of Depression and Anxiety Symptoms (IDAS) were identified as HS+. Participants provided daily ratings of symptoms throughout the study via the Daily Record of Severity of Problems. Results indicated that HS+ participants could be differentiated from HS- participants early in the hormone protocol, with many symptoms showing significantly greater change from baseline within the first week of addback. Notably, the most rapid symptom increases were observed for Anger/Irritability, Mood Swings, Overwhelm, Lethargy, Increased Appetite, Joint and Muscle Pain, and Breast Tenderness, reaching 50% of peak group contrast within the first week of hormone addback. The largest group effects were observed for Anger/Irritability, followed by Fatigue and Anxiety, and the most consistent group effects were observed for Anger/Irritability, Interpersonal Conflict, Overwhelm, and Hopelessness. Findings support the role of reproductive hormones in the onset of perinatal affective disorders. The rapid emergence of anger and irritability in HS+ participants suggests that these symptoms may be early indicators of perinatal hormone sensitivity.


Assuntos
Depressão Pós-Parto , Transtorno Depressivo Maior , Gravidez , Humanos , Feminino , Masculino , Transtorno Depressivo Maior/diagnóstico , Estradiol , Parto , Modelos Teóricos
4.
JSLS ; 27(2)2023.
Artigo em Inglês | MEDLINE | ID: mdl-37522106

RESUMO

Background and Objectives: Robotic gynecologic surgery has outpaced data showing risks and benefits related to cost, quality outcomes, and patient safety. We aimed to assess how credentialing standards and perceptions of safe use of robotic gynecologic surgery have changed over time. Methods: An anonymous, online survey was distributed in 2013 and in 2021 to attending surgeons and trainees in accredited obstetrics and gynecology residency programs. Results: There were 367 respondents; 265 in 2013 and 102 in 2021. There was a significant increase in robotic platform use from 2013 to 2021. Percentage of respondents who ever having performed a robotic case increased from 48% to 79% and those who performed > 50 cases increased from 25% to 59%. In 2021, a greater percentage of attending physicians reported having formalized protocol for obtaining robotic credentials (93% vs 70%, p = 0.03) and maintaining credentialing (90% vs 27%, p < 0.01). At both time points, most attendings reported requiring proctoring for 1 - 5 cases before independent use. Opinions on the number of cases needed for surgical independence changed from 2013 to 2021. There was an increase in respondents who believed > 20 cases were required (from 58% to 93% of trainees and 29% to 70% of attendings). In 2021, trainees were less likely to report their attendings lacked the skills to safely perform robotic surgery (25% to 6%, p < 0.01). Discussion: Greater experience with robotic platforms and expansion of credentialing processes over time correlated with improved confidence in surgeon skills. Further work is needed to evaluate if current credentialing procedures are sufficient.


Assuntos
Internato e Residência , Procedimentos Cirúrgicos Robóticos , Feminino , Humanos , Segurança do Paciente , Procedimentos Cirúrgicos em Ginecologia/métodos , Credenciamento
5.
J Minim Invasive Gynecol ; 30(8): 627-634, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37037283

RESUMO

STUDY OBJECTIVE: To examine national trends among race and ethnicity and route of benign hysterectomy from 2007 to 2018. DESIGN: This is a retrospective analysis of the prospective National Surgical Quality Improvement Program cohort program. SETTING: This study included data from the National Surgical Quality Improvement Program database including data from the 2014 to 2018 targeted hysterectomy files. PATIENTS: Adult patients undergoing hysterectomy. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: Current Procedural Terminology codes identified women undergoing benign hysterectomy and perioperative data including race and ethnicity were obtained. To determine relative trends in hysterectomy among race and ethnicity cohorts (White, Black, Hispanic), we calculated the proportion of each procedure performed annually within each race and ethnicity group and compared it across groups. From 2007 to 2018, 269 794 hysterectomies were collected (190 154 White, 45 756 Black, and 33 884 Hispanic). From 2007 to 2018, rates of laparoscopic hysterectomy increased in all cohorts (30.2%-71.6% for White, 23.9%-58.5% for Black, 19.9%-64.0% for Hispanic; ptrend <0.01 for all). For each year from 2007 to 2018, the proportion of women undergoing open abdominal hysterectomy remained twice as high in Black Women compared with White women (33.1%-14.4%, p <.01). Data from the 2014 to 2018 targeted files showed Black and Hispanic women undergoing benign hysterectomy were generally younger, had larger uteri, were more likely to be current smokers, have diabetes and/or hypertension, have higher body mass index, and have undergone previous pelvic surgery (p ≤.01 for all). CONCLUSION: Compared with White women, Black and Hispanic women are less likely to undergo benign hysterectomy via a minimally invasive approach. Although larger uteri and comorbid conditions may attribute to higher rates of open abdominal hysterectomy, the higher prevalence of abdominal hysterectomy among younger Black and Hispanic women highlights potential racial disparities in women's health and access to care.


Assuntos
Etnicidade , Histerectomia , Adulto , Feminino , Humanos , Estados Unidos/epidemiologia , Estudos Retrospectivos , Estudos Prospectivos , Histerectomia/efeitos adversos , Histerectomia/métodos , Complicações Pós-Operatórias/etiologia , Disparidades em Assistência à Saúde
6.
Trials ; 24(1): 150, 2023 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-36855177

RESUMO

BACKGROUND: The perimenopausal transition is accompanied by psychiatric symptoms in over 10% of women. Symptoms commonly include depressed mood and anhedonia and less commonly include psychosis. Psychiatric symptoms have been linked to the depletion and/or variability of circulating estradiol, and estradiol treatment reduces perimenopausal anhedonia and psychosis in some women. Estrogen fluctuations may disrupt function in the mesolimbic reward system in some women, leading to psychiatric symptoms like anhedonia or psychosis. The Perimenopausal Effects of Estradiol on Anhedonia and Psychosis Study (PEEPs) is a mechanistic clinical trial that aims to (1) identify relationships between perimenopausal-onset anhedonia and psychosis and neuromolecular markers of mesolimbic reward responses and (2) determine the extent to which estradiol treatment-induced changes in mesolimbic reward responses are associated with alleviation of perimenopausal onset anhedonia or psychosis. METHODS: This study will recruit 100 unmedicated women ages 44-55 in the late-stage perimenopausal transition, sampling across the range of mild-to-high anhedonia and absent-to-moderate psychosis symptoms. Patients will be randomized to receive either estradiol or placebo treatment for 3 weeks. Clinical outcome measures will include symptoms of anhedonia (measured with Snaith-Hamilton Pleasure Scale; SHAPS) and psychosis (measured with Brief Psychiatric Rating Scale; BPRS psychosis subscale) as well as neural markers of mesolimbic reward system functioning, including reward-related fMRI activation and PET-derived measure of striatal dopamine binding. Pre-treatment associations between (1) SHAPS/BPRS scores and (2) reward-related striatal dopamine binding/BOLD activation will be examined. Furthermore, longitudinal mixed models will be used to estimate (1) symptom and neuromolecular trajectories as a function of estradiol vs. placebo treatment and (2) how changes in reward-related striatal dopamine binding and BOLD activation predict variability in symptom trajectories in response to estradiol treatment. DISCUSSION: This clinical trial will be the first to characterize neural and molecular mechanisms by which estradiol treatment ameliorates anhedonia and psychosis symptoms during the perimenopausal transition, thus laying the groundwork for future biomarker research to predict susceptibility and prognosis and develop targeted treatments for perimenopausal psychiatric symptoms. Furthermore, in alignment with the National Institute for Mental Health Research Domain Criteria initiative, this trial will improve our understanding of a range of disorders characterized by anhedonia, psychosis, and reward system dysfunction. TRIAL REGISTRATION: ClinicalTrials.gov NCT05282277.


Assuntos
Estradiol , Transtornos Psicóticos , Feminino , Humanos , Estradiol/uso terapêutico , Anedonia , Dopamina , Perimenopausa , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto
7.
Obstet Gynecol ; 141(3): 622-623, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36800858
8.
STAR Protoc ; 3(4): 101829, 2022 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-36386871

RESUMO

Large-scale, high-throughput specificity assays to characterize binding properties within a competitive and complex environment of potential binder-target pairs remain challenging and cost prohibitive. Barcode cycle sequencing (BCS) is a molecular binding assay for proteins, peptides, and other small molecules that is built on a next-generation sequencing (NGS) chip. BCS uses a binder library and targets labeled with unique DNA barcodes. Upon binding, binder barcodes are ligated to target barcodes and sequenced to identify encoded binding events. For complete details on the use and execution of this protocol, please refer to Hong et al. (2022).


Assuntos
Código de Barras de DNA Taxonômico , Sequenciamento de Nucleotídeos em Larga Escala , Biblioteca Gênica , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Análise de Sequência de DNA/métodos , Código de Barras de DNA Taxonômico/métodos , Sequência de Bases
9.
Obstet Gynecol ; 140(5): 739-742, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36201760

RESUMO

Disparities in health by race, ethnicity, and socioeconomic status within obstetrics and gynecology are well described and prompt evaluation for structural barriers. Academic medicine has a historical role in caring for marginalized populations, with medical trainees often serving as first-line clinicians for outpatient care. The ubiquitous approach of concentrating care of marginalized patients within resident and trainee clinics raises ethical questions regarding equity and sends a clear message of value that is internalized by learners and patients. A path forward is elimination of the structural inequities caused by maintenance of clinics stratified by training level, thereby creating an integrated patient pool for trainees and attending physicians alike. In this model, demographic and insurance information is blinded and patient triage is guided by clinical acuity and patient preference alone. To address structural inequities in our health care delivery system, we implemented changes in our department. Our goals were to improve access and patient experience and to send a unified message to our patients, learners, and faculty-our clinical staff, across all training levels, are committed to giving the highest standard of care to all people, regardless of insurance status or ability to pay. Academic medical centers must look internally for structural barriers that contribute to health care disparities within obstetrics and gynecology as we aim to make progress toward equity.


Assuntos
Ginecologia , Obstetrícia , Humanos , Ginecologia/educação , Obstetrícia/educação , Disparidades em Assistência à Saúde , Cobertura do Seguro , Centros Médicos Acadêmicos
10.
Nat Commun ; 13(1): 1590, 2022 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-35338121

RESUMO

Drug discovery for diseases such as Parkinson's disease are impeded by the lack of screenable cellular phenotypes. We present an unbiased phenotypic profiling platform that combines automated cell culture, high-content imaging, Cell Painting, and deep learning. We applied this platform to primary fibroblasts from 91 Parkinson's disease patients and matched healthy controls, creating the largest publicly available Cell Painting image dataset to date at 48 terabytes. We use fixed weights from a convolutional deep neural network trained on ImageNet to generate deep embeddings from each image and train machine learning models to detect morphological disease phenotypes. Our platform's robustness and sensitivity allow the detection of individual-specific variation with high fidelity across batches and plate layouts. Lastly, our models confidently separate LRRK2 and sporadic Parkinson's disease lines from healthy controls (receiver operating characteristic area under curve 0.79 (0.08 standard deviation)), supporting the capacity of this platform for complex disease modeling and drug screening applications.


Assuntos
Aprendizado Profundo , Doença de Parkinson , Fibroblastos , Humanos , Aprendizado de Máquina , Redes Neurais de Computação
11.
iScience ; 25(1): 103586, 2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35005536

RESUMO

We demonstrate early progress toward constructing a high-throughput, single-molecule protein sequencing technology utilizing barcoded DNA aptamers (binders) to recognize terminal amino acids of peptides (targets) tethered on a next-generation sequencing chip. DNA binders deposit unique, amino acid-identifying barcodes on the chip. The end goal is that, over multiple binding cycles, a sequential chain of DNA barcodes will identify the amino acid sequence of a peptide. Toward this, we demonstrate successful target identification with two sets of target-binder pairs: DNA-DNA and Peptide-Protein. For DNA-DNA binding, we show assembly and sequencing of DNA barcodes over six consecutive binding cycles. Intriguingly, our computational simulation predicts that a small set of semi-selective DNA binders offers significant coverage of the human proteome. Toward this end, we introduce a binder discovery pipeline that ultimately could merge with the chip assay into a technology called ProtSeq, for future high-throughput, single-molecule protein sequencing.

12.
Obstet Gynecol ; 138(5): 715-724, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34619742

RESUMO

OBJECTIVE: To assess whether preoperative depression or anxiety is associated with increased risk of long-term, postoperative opioid use after hysterectomy among women who are opioid-naïve. METHODS: We conducted an observational cohort study of 289,233 opioid-naïve adult women (18 years or older) undergoing hysterectomy for benign indications from 2010 to 2017 using IBM MarketScan databases. Opioid use and refills in the 180 days after surgery and preoperative depression and anxiety were assessed. Secondary outcomes included 30-day incidence of emergency department visits, readmission, and 180-day incidence of opioid complications. The association of depression and anxiety were compared using inverse-probability of treatment weighted log-binomial and proportional Cox regression. RESULTS: Twenty-one percent of women had preoperative depression or anxiety, and 82% of the entire cohort had a perioperative opioid fill (16% before surgery, 66% after surgery). Although perioperative opioid fills were relatively similar across the two groups (risk ratio [RR] 1.07, 95% CI 1.06-1.07), women with depression or anxiety were significantly more likely to have a postoperative opioid fill at every studied time period (RRs 1.44-1.50). Differences were greater when restricted to persistent use (RRs 1.49-2.61). Although opioid complications were rare, women with depression were substantially more likely to be diagnosed with opioid dependence (hazard ratio [HR] 5.54, 95% CI 4.12-7.44), and opioid use disorder (HR 4.20, 95% CI 1.97-8.96). CONCLUSION: Perioperative opioid fills are common after hysterectomy. Women with preoperative anxiety and depression are more likely to experience persistent use and opioid-related complications.


Assuntos
Analgésicos Opioides/efeitos adversos , Ansiedade/epidemiologia , Depressão/epidemiologia , Histerectomia/efeitos adversos , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Adulto , Analgésicos Opioides/uso terapêutico , Estudos de Coortes , Prescrições de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Histerectomia/estatística & dados numéricos , Pessoa de Meia-Idade , Transtornos Relacionados ao Uso de Opioides/etiologia , Dor Pós-Operatória/tratamento farmacológico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
13.
Obstet Gynecol ; 137(4): 648-656, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33706344

RESUMO

OBJECTIVE: To assess whether a superior hypogastric plexus block performed during laparoscopic hysterectomy reduces postoperative pain. METHODS: We conducted a multicenter, randomized, single-blind, controlled trial of superior hypogastric plexus block at the start of laparoscopic hysterectomy. Women undergoing a laparoscopic hysterectomy for any indication and with any other concomitant laparoscopic procedure were eligible. Standardized preoperative medications and incisional analgesia were provided to all patients. Our primary outcome was the proportion of patients with a mean visual analog scale (VAS) pain score lower than 4 within 2 hours postoperatively. Patients but not surgeons were blinded to the treatment group. Twenty-nine patients per group was estimated to be sufficient to detect a 38% absolute difference in the proportion of patients with a VAS score lower than 4 at 2 hours postoperatively, with 80% power and an α of 0.05. To account for loss to follow-up and potential imbalances in patient characteristics, we planned to enroll 50 patients per group. All analyses were intention to treat. RESULTS: Between January 2018 and February 2019, 186 patients were eligible; 100 were randomized and analyzed. Demographic and clinical characteristics were similar between the two groups. There was no significant difference in the proportion of patients with a mean VAS score lower than 4 within 2 hours postoperatively between patients who received a superior hypogastric plexus block (57%) and patients who did not (43%) (odds ratio 1.63, 95% CI 0.74-3.59; adjusted odds ratio 1.84, 95% CI 0.75-4.51). CONCLUSION: Among patients undergoing laparoscopic hysterectomy with standardized enhanced perioperative recovery pathways, superior hypogastric plexus block did not significantly reduce postoperative pain. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03283436.


Assuntos
Plexo Hipogástrico , Histerectomia , Laparoscopia , Bloqueio Nervoso , Dor Pós-Operatória/prevenção & controle , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Medição da Dor , Resultado do Tratamento , Estados Unidos
14.
Stem Cell Reports ; 14(4): 631-647, 2020 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-32243845

RESUMO

Epithelial to mesenchymal transition (EMT) is a biological process involved in tissue morphogenesis and disease that causes dramatic changes in cell morphology, migration, proliferation, and gene expression. The retinal pigment epithelium (RPE), which supports the neural retina, can undergo EMT, producing fibrous epiretinal membranes (ERMs) associated with vision-impairing clinical conditions, such as macular pucker and proliferative vitreoretinopathy (PVR). We found that co-treatment with TGF-ß and TNF-α (TNT) accelerates EMT in adult human RPE stem cell-derived RPE cell cultures. We captured the global epigenomic and transcriptional changes elicited by TNT treatment of RPE and identified putative active enhancers associated with actively transcribed genes, including a set of upregulated transcription factors that are candidate regulators. We found that the vitamin B derivative nicotinamide downregulates these key transcriptional changes, and inhibits and partially reverses RPE EMT, revealing potential therapeutic routes to benefit patients with ERM, macular pucker and PVR.


Assuntos
Epigenômica , Membrana Epirretiniana/prevenção & controle , Transição Epitelial-Mesenquimal , Modelos Biológicos , Niacinamida/uso terapêutico , Epitélio Pigmentado da Retina/patologia , Células-Tronco/metabolismo , Transcriptoma/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Elementos Facilitadores Genéticos/genética , Membrana Epirretiniana/patologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Niacinamida/genética , Niacinamida/farmacologia , Fenótipo , Células-Tronco/efeitos dos fármacos , Fatores de Transcrição/metabolismo , Transcrição Gênica/efeitos dos fármacos , Fator de Crescimento Transformador beta1/farmacologia , Fator de Necrose Tumoral alfa/farmacologia
15.
PLoS One ; 15(1): e0220214, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31923185

RESUMO

BACKGROUND: Robotic surgery presents a challenge to effective teamwork and communication in the operating theatre (OR). Our objective was to evaluate the effect of using a wireless audio headset device on communication, efficiency and patient outcome in robotic surgery. METHODS AND FINDINGS: A prospective controlled trial of team members participating in gynecologic and urologic robotic procedures between January and March 2015. In the first phase, all surgeries were performed without headsets (control), followed by the intervention phase where all team members used the wireless headsets. Noise levels were measured during both phases. After each case, all team members evaluated the quality of communication, performance, teamwork and mental load using a validated 14-point questionnaire graded on a 1-10 scale. Higher overall scores indicated better communication and efficiency. Clinical and surgical data of all patients in the study were retrieved, analyzed and correlated with the survey results. The study included 137 procedures, yielding 843 questionnaires with an overall response rate of 89% (843/943). Self-reported communication quality was better in cases where headsets were used (113.0 ± 1.6 vs. 101.4 ± 1.6; p < .001). Use of headsets reduced the percentage of time with a noise level above 70 dB at the console (8.2% ± 0.6 vs. 5.3% ± 0.6, p < .001), but had no significant effect on length of surgery nor postoperative complications. CONCLUSIONS: The use of wireless headset devices improved quality of communication between team members and reduced the peak noise level in the robotic OR.


Assuntos
Recursos Audiovisuais , Procedimentos Cirúrgicos em Ginecologia/instrumentação , Laparoscopia/instrumentação , Procedimentos Cirúrgicos Robóticos/instrumentação , Procedimentos Cirúrgicos Urológicos/instrumentação , Tecnologia sem Fio/instrumentação , Idoso , Comunicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários
16.
Anesth Analg ; 129(3): 776-783, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31425219

RESUMO

BACKGROUND: Enhanced recovery after surgery (ERAS) pathways in gynecologic surgery have been shown to decrease length of stay with no impact on readmission, but no study has assessed predictors of admission in this population. The purpose of this study was to identify predictors of admission after laparoscopic hysterectomy (LH) and robotic-assisted hysterectomy (RAH) performed under an ERAS pathway. METHODS: This is a prospective observational study of women undergoing LH/RAH for benign indications within an ERAS pathway. Data collected included same-day discharge, reason for admission, incidences of urgent clinic and emergency room (ER) visits, readmissions, reoperations, and 9 postulated predictors of admission listed below. Patient demographics, markers of baseline health, and clinical outcomes were compared between groups (ERAS patients discharged on the day of surgery versus admitted) using Fisher exact and Student t tests. Multivariable logistic regression was used to assess the potential risk factors for being admitted, adjusting for age, race, body mass index, American Society of Anesthesiologists (ASA) physical status score, preoperative diagnosis indicative of hysterectomy, preoperative chronic pain, completion of a preprocedure pain-coping skills counseling session, procedure time, and compliance to the ERAS pathway. RESULTS: There were 165 patients undergoing LH/RAH within an ERAS pathway; 93 (56%) were discharged on the day of surgery and 72 were admitted. There were no significant differences in ER visits, readmissions, and reoperations between groups (ER visits: discharged 13% versus admitted 13%, P = .99; 90-day readmission: discharged 4% versus admitted 7%, P = .51; and 90-day reoperation: discharged 4% versus admitted 3%, P = .70). The most common reasons for admission were postoperative urinary retention (n = 21, 30%), inadequate pain control (n = 21, 30%), postoperative nausea and vomiting (n = 7, 10%), and planned admissions (n = 7, 10%). Increased ASA physical status, being African American, and increased length of procedure were significantly associated with an increased risk of admission (ASA physical status III versus ASA physical status I or II: odds ratio [OR], 3.12; 95% confidence interval [CI], 1.36-7.16; P = .007; African American: OR, 2.47; 95% CI, 1.02-5.96; P = .04; and length of procedure, assessed in 30-minute increments: OR, 1.23; 95% CI, 1.02-1.50; P = .04). CONCLUSIONS: We were able to define predictors of admission for patients having LH/RAH managed with an ERAS pathway. Increased ASA physical status, being African American, and increased length of procedure were significantly associated with admission after LH/RAH performed under an ERAS pathway. In addition, the incidences of urgent clinic and ER visits, readmissions, and reoperations within 90 days of surgery were similar for patients who were discharged on the day of surgery compared to those admitted.


Assuntos
Recuperação Pós-Cirúrgica Melhorada , Procedimentos Cirúrgicos em Ginecologia/tendências , Procedimentos Cirúrgicos Minimamente Invasivos/tendências , Admissão do Paciente/tendências , Adulto , Feminino , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Humanos , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Valor Preditivo dos Testes , Estudos Prospectivos , Estudos Retrospectivos
17.
Endosc Int Open ; 7(6): E837-E840, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31198849

RESUMO

Background and study aims Endometriosis affects a significant proportion of reproductive-aged women and involves the bowel in up to one-third of patients with the condition. Lower endoscopic ultrasound (LEUS) in assessment of endometriosis of the rectosigmoid colon was first described 20 years ago in European populations. The current study aimed to describe the diagnostic characteristics of this imaging modality at a tertiary US referral center in a large cohort and its impact on surgical planning. Patients and methods This was a retrospective cohort study of adult women evaluated for rectosigmoid endometriosis by LEUS at an American tertiary referral center between January 2003 through June 2017. The reference standard for rectosigmoid endometriosis was surgical evaluation regardless of whether tissue was obtained for histologic evaluation. Two separate analyses were run; one comparing EUS to laparoscopic findings and another comparing EUS to histologic findings. Results LEUS demonstrated a positive predictive value (PPV) of 93.8 % (CI:68.1,99.1) and negative predictive value (NPV) of 96.4 % (CI:87.8,99.0) in the diagnosis of rectosigmoid endometriosis. Test sensitivity was 88.2 % (CI:63.6,98.5) and specificity was 98.2 % (CI:90.1,99.9). Overall diagnostic accuracy of the test was 95.8 % (CI:88.1,99.1). Conclusions In this large cohort of women at an American tertiary referral center undergoing evaluation for rectosigmoid endometriosis, LEUS demonstrated high PPV and NPV as well as excellent diagnostic accuracy. In addition, the LEUS findings provided important information to the referring gynecologic surgeon. This minimally-invasive imaging modality should be utilized in preoperative evaluation of women undergoing surgery for suspected or known endometriosis.

18.
Commun Biol ; 2: 162, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31069271

RESUMO

Proliferative vitreoretinopathy (PVR) is a metaplasia in the vitreous of the eye manifested by the transformation of retinal pigment epithelial (RPE) cells and the development of contracting epiretinal membranes (ERM), which lead to retinal detachment and vision loss. While TGFß1 and TNFα have been associated with PVR, here we show that these cytokines act synergistically to induce an aggressive contraction phenotype on adult human (ah)RPE. Connected RPE detach upon contraction and form motile membranes that recruit more cells. TGFß1 and TNFα (TNT)-induced contracting membranes uniquely express muscle and extracellular rearrangement genes. Whole transcriptome RNA sequencing of patient-dissected PVR membranes showed activation of the p38-MAPK signaling pathway. Inhibition of p38 during TNT treatment blocks ahRPE transformation and membrane contraction. Furthermore, TNT-induced membrane contractility can be reversed by p38 inhibition after induction. Therefore, targeting the p38-MAPK pathway may have therapeutic benefits for patients with PVR even after the onset of contracting ERMs.


Assuntos
Membrana Epirretiniana/genética , Descolamento Retiniano/genética , Fator de Crescimento Transformador beta1/genética , Fator de Necrose Tumoral alfa/genética , Vitreorretinopatia Proliferativa/genética , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Movimento Celular , Membrana Epirretiniana/metabolismo , Membrana Epirretiniana/patologia , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Cultura Primária de Células , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Descolamento Retiniano/metabolismo , Descolamento Retiniano/patologia , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/patologia , Transdução de Sinais , Imagem com Lapso de Tempo , Transcriptoma , Fator de Crescimento Transformador beta1/antagonistas & inibidores , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta1/farmacologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Vitreorretinopatia Proliferativa/metabolismo , Vitreorretinopatia Proliferativa/patologia , Corpo Vítreo/metabolismo , Corpo Vítreo/patologia , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
19.
Int J Gynaecol Obstet ; 145(3): 293-299, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30929251

RESUMO

OBJECTIVE: To assess the effect of length of hospital stay on postoperative outcomes after minimally invasive hysterectomy. METHODS: A retrospective cohort analysis was conducted of women who underwent minimally invasive hysterectomy (vaginal or laparoscopic) for benign conditions between January 1, 2014 and December 31, 2016, using the American College of Surgeons National Surgical Quality Improvement Program database. Patient information and 30-day outcomes were compared using multivariable logistic regression after adjusting for patient demographics and medical and procedure variables. RESULTS: The analysis included 31 347 patients. Women discharged the day after surgery were more likely to be African-American, older, have prior abdominal surgery, and a higher ASA classification. Prevalence of organ space infection and readmissions were lower in the same day discharge group. No differences between same- and next-day discharge were found for surgical site infection or urinary tract infection (adjusted odds ratios (aORs) 0.83 (95% [CI] 0.65-1.07; P=0.156) and 0.85 (95% CI 0.68-1.06; P=0.151), respectively). Same-day hospital discharge was associated with a reduced chance of readmission (aOR=0.68, 95% CI 0.54-0.87; P=0.002). CONCLUSION: Same-day hospital discharge after minimally invasive hysterectomy lowered the risk of readmission and did not increase the risk of postoperative complications.


Assuntos
Histerectomia/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Readmissão do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Adulto , Feminino , Humanos , Histerectomia/métodos , Laparoscopia/métodos , Modelos Logísticos , Pessoa de Meia-Idade , Razão de Chances , Melhoria de Qualidade , Estudos Retrospectivos
20.
J Minim Invasive Gynecol ; 26(7): 1327-1333, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30639320

RESUMO

STUDY OBJECTIVE: To describe the accuracy of historic averages for estimating operating room (OR) time for hysterectomy among women with small and large uteri. DESIGN: A retrospective cohort study. SETTING: Data from women who underwent abdominal, vaginal, or laparoscopic hysterectomy between 2015 and 2017 at the University of North Carolina Hospitals were analyzed. Historic and actual OR times were compared using linear regression. Patient characteristics were also evaluated to determine whether they were associated with the accuracy of predicted OR times. PATIENTS: Nine hundred eighty-five adult women (≥18 years old) who underwent surgery for benign indications or for suspected but not biopsy-confirmed malignancy were included. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: Historic averages overestimated OR time by a median of 14 minutes (interquartile range [IQR] = -29 to 49 minutes). The OR time in women with small uteri (<250 g) was significantly more likely to be overestimated than women with large uteri (≥250 g) (median time = 21 minutes [IQR = -16 to 52 minutes] and 3 minutes [IQR = -38 to 44 minutes], respectively; p <. 001). In total laparoscopic hysterectomy and laparoscopy-assisted vaginal hysterectomy, women with uteri ≥250 g took significantly longer than hysterectomy for women with uteri <250 g (36 minutes longer [95% confidence interval, 24-50] and 95 minutes longer [95% confidence interval, 12-179], respectively; p < .001 and p = .03). CONCLUSION: Using historic averages overestimates OR time, and it is more pronounced in women with small uteri. However, there is a relatively large range of OR times, even among women with the same size uteri. This study highlights the importance of preoperative planning, and in cases in which endometriosis is expected, manually adding time to estimates is recommended.


Assuntos
Histerectomia/estatística & dados numéricos , Duração da Cirurgia , Anormalidades Urogenitais/patologia , Útero/anormalidades , Útero/patologia , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Tamanho do Órgão , Estudos Retrospectivos , Anormalidades Urogenitais/cirurgia , Útero/cirurgia
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