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1.
medRxiv ; 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38826471

RESUMEN

Background: Anaesthesiology clinicians can implement risk mitigation strategies if they know which patients are at greatest risk for postoperative complications. Although machine learning models predicting complications exist, their impact on clinician risk assessment is unknown. Methods: This single-centre randomised clinical trial enrolled patients age ≥18 undergoing surgery with anaesthesiology services. Anaesthesiology clinicians providing remote intraoperative telemedicine support reviewed electronic health records with (assisted group) or without (unassisted group) also reviewing machine learning predictions. Clinicians predicted the likelihood of postoperative 30-day all-cause mortality and postoperative acute kidney injury within 7 days. Area under the receiver operating characteristic curve (AUROC) for the clinician predictions was determined. Results: Among 5,071 patient cases reviewed by 89 clinicians, the observed incidence was 2% for postoperative death and 11% for acute kidney injury. Clinician predictions agreed with the models more strongly in the assisted versus unassisted group (weighted kappa 0.75 versus 0.62 for death [difference 0.13, 95%CI 0.10-0.17] and 0.79 versus 0.54 for kidney injury [difference 0.25, 95%CI 0.21-0.29]). Clinicians predicted death with AUROC of 0.793 in the assisted group and 0.780 in the unassisted group (difference 0.013, 95%CI -0.070 to 0.097). Clinicians predicted kidney injury with AUROC of 0.734 in the assisted group and 0.688 in the unassisted group (difference 0.046, 95%CI -0.003 to 0.091). Conclusions: Although there was evidence that the models influenced clinician predictions, clinician performance was not statistically significantly different with and without machine learning assistance. Further work is needed to clarify the role of machine learning in real-time perioperative risk stratification. Trial Registration: ClinicalTrials.gov NCT05042804.

2.
medRxiv ; 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38826207

RESUMEN

Background: Novel applications of telemedicine can improve care quality and patient outcomes. Telemedicine for intraoperative decision support has not been rigorously studied. Methods: This single centre randomised clinical trial ( clinicaltrials.gov NCT03923699 ) of unselected adult surgical patients was conducted between July 1, 2019 and January 31, 2023. Patients received usual care or decision support from a telemedicine service, the Anesthesiology Control Tower (ACT). The ACT provided real-time recommendations to intraoperative anaesthesia clinicians based on case reviews, machine-learning forecasting, and physiologic alerts. ORs were randomised 1:1. Co-primary outcomes of 30-day all-cause mortality, respiratory failure, acute kidney injury (AKI), and delirium were analysed as intention-to-treat. Results: The trial completed planned enrolment with 71927 surgeries (35956 ACT; 35971 usual care). After multiple testing correction, there was no significant effect of the ACT vs. usual care on 30-day mortality [641/35956 (1.8%) vs 638/35971 (1.8%), risk difference 0.0% (95% CI -0.2% to 0.3%), p=0.96], respiratory failure [1089/34613 (3.1%) vs 1112/34619 (3.2%), risk difference -0.1% (95% CI -0.4% to 0.3%), p=0.96], AKI [2357/33897 (7%) vs 2391/33795 (7.1%), risk difference -0.1% (-0.6% to 0.4%), p=0.96], or delirium [1283/3928 (32.7%) vs 1279/3989 (32.1%), risk difference 0.6% (-2.0% to 3.2%), p=0.96]. There were no significant differences in secondary outcomes or in sensitivity analyses. Conclusions: In this large RCT of a novel application of telemedicine-based remote monitoring and decision support using real-time alerts and case reviews, we found no significant differences in postoperative outcomes. Large-scale intraoperative telemedicine is feasible, and we suggest future avenues where it may be impactful.

3.
Anesth Analg ; 138(4): 804-813, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-37339083

RESUMEN

BACKGROUND: Machine learning models can help anesthesiology clinicians assess patients and make clinical and operational decisions, but well-designed human-computer interfaces are necessary for machine learning model predictions to result in clinician actions that help patients. Therefore, the goal of this study was to apply a user-centered design framework to create a user interface for displaying machine learning model predictions of postoperative complications to anesthesiology clinicians. METHODS: Twenty-five anesthesiology clinicians (attending anesthesiologists, resident physicians, and certified registered nurse anesthetists) participated in a 3-phase study that included (phase 1) semistructured focus group interviews and a card sorting activity to characterize user workflows and needs; (phase 2) simulated patient evaluation incorporating a low-fidelity static prototype display interface followed by a semistructured interview; and (phase 3) simulated patient evaluation with concurrent think-aloud incorporating a high-fidelity prototype display interface in the electronic health record. In each phase, data analysis included open coding of session transcripts and thematic analysis. RESULTS: During the needs assessment phase (phase 1), participants voiced that (a) identifying preventable risk related to modifiable risk factors is more important than nonpreventable risk, (b) comprehensive patient evaluation follows a systematic approach that relies heavily on the electronic health record, and (c) an easy-to-use display interface should have a simple layout that uses color and graphs to minimize time and energy spent reading it. When performing simulations using the low-fidelity prototype (phase 2), participants reported that (a) the machine learning predictions helped them to evaluate patient risk, (b) additional information about how to act on the risk estimate would be useful, and (c) correctable problems related to textual content existed. When performing simulations using the high-fidelity prototype (phase 3), usability problems predominantly related to the presentation of information and functionality. Despite the usability problems, participants rated the system highly on the System Usability Scale (mean score, 82.5; standard deviation, 10.5). CONCLUSIONS: Incorporating user needs and preferences into the design of a machine learning dashboard results in a display interface that clinicians rate as highly usable. Because the system demonstrates usability, evaluation of the effects of implementation on both process and clinical outcomes is warranted.


Asunto(s)
Diseño Centrado en el Usuario , Interfaz Usuario-Computador , Humanos , Grupos Focales , Registros Electrónicos de Salud , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control
4.
Microbiol Spectr ; 12(1): e0263823, 2024 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-38088549

RESUMEN

IMPORTANCE: Untreated asymptomatic bacteriuria (ASB) has been associated with adverse pregnancy outcomes, including pyelonephritis, preterm labor, and low birth weight infants. Thus, routine screening by standard urine culture (SUC) and treatment of ASB are currently recommended for all pregnant women. For this purpose, some researchers claim that vaginal swabs and urine samples can be used as proxies for each other. Because SUC often misses microbes, we used two more sensitive, recently validated detection methods to compare the composition of the urinary and vaginal microbiomes of pregnant females in their first trimester. Both methods yielded similar results. Vaginal and urinary microbial compositions for the same individual were significantly correlated; however, they were not equivalent. We argue that first trimester urinary and vaginal microbiomes are distinct enough to preclude their use as proxies for each other.


Asunto(s)
Bacteriuria , Complicaciones Infecciosas del Embarazo , Pielonefritis , Sistema Urinario , Recién Nacido , Embarazo , Femenino , Humanos , Primer Trimestre del Embarazo , Complicaciones Infecciosas del Embarazo/diagnóstico , Complicaciones Infecciosas del Embarazo/microbiología , Bacteriuria/diagnóstico , Bacteriuria/microbiología
5.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-1013465

RESUMEN

Background@#Ovarian, fallopian tube, and peritoneal cancer patients with advanced-stage diagnosis or recurrences spread to the peritoneal surface of the abdomen. Hyperthermic intraperitoneal chemotherapy (HIPEC) can penetrate and eradicate tumors that are microscopic up to those with a diameter of 2.5 cm from the peritoneal surface following cytoreductive surgery (CRS). @*Objectives@#The study aimed to determine the efficacy and safety of CRS with HIPEC versus CRS alone for patients with epithelial ovarian, fallopian tube, and peritoneal cancer. @*Materials and Methods@#This retrospective cohort study included 50 patients (20 patients underwent CRS + HIPEC, while 30 patients underwent CRS alone). Records of these patients from January 2014 to June 2020 were reviewed, tabulated, and analyzed.@*Results@#The difference in recurrence rate between CRS with HIPEC and CRS alone was not statistically significant (50% vs. 43%, P = 0.774). The median time to recurrence was 10 and 9 months, respectively (P = 0.636). Five percent in the HIPEC group succumbed to the disease, while 13% died in the CRS alone group (P = 0.636). More post-operative complications were noted in the HIPEC group (45% vs. 10%, P = 0.007), but among these, only 2 cases had grade 3 to 4 complications (10%). The addition of HIPEC in the management of these patients resulted in a longer operative time (360 vs. 240 min, P < 0.001) and postoperative hospital stay (8 vs. 6 days, P = 0.026). There were no intra- or peri-operative mortalities in both groups.@*Conclusion@#CRS with HIPEC and CRS alone showed similar time to recurrence and recurrence rate. CRS with HIPEC had low risk of grade 3-4 complications and may still be considered as a treatment option for advanced, progressive, and recurrent epithelial ovarian, fallopian tube, and peritoneal cancer.


Asunto(s)
Procedimientos Quirúrgicos de Citorreducción , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Ováricas
6.
JAMA Netw Open ; 6(9): e2332517, 2023 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-37738052

RESUMEN

Importance: Telemedicine for clinical decision support has been adopted in many health care settings, but its utility in improving intraoperative care has not been assessed. Objective: To pilot the implementation of a real-time intraoperative telemedicine decision support program and evaluate whether it reduces postoperative hypothermia and hyperglycemia as well as other quality of care measures. Design, Setting, and Participants: This single-center pilot randomized clinical trial (Anesthesiology Control Tower-Feedback Alerts to Supplement Treatments [ACTFAST-3]) was conducted from April 3, 2017, to June 30, 2019, at a large academic medical center in the US. A total of 26 254 adult surgical patients were randomized to receive either usual intraoperative care (control group; n = 12 980) or usual care augmented by telemedicine decision support (intervention group; n = 13 274). Data were initially analyzed from April 22 to May 19, 2021, with updates in November 2022 and February 2023. Intervention: Patients received either usual care (medical direction from the anesthesia care team) or intraoperative anesthesia care monitored and augmented by decision support from the Anesthesiology Control Tower (ACT), a real-time, live telemedicine intervention. The ACT incorporated remote monitoring of operating rooms by a team of anesthesia clinicians with customized analysis software. The ACT reviewed alerts and electronic health record data to inform recommendations to operating room clinicians. Main Outcomes and Measures: The primary outcomes were avoidance of postoperative hypothermia (defined as the proportion of patients with a final recorded intraoperative core temperature >36 °C) and hyperglycemia (defined as the proportion of patients with diabetes who had a blood glucose level ≤180 mg/dL on arrival to the postanesthesia recovery area). Secondary outcomes included intraoperative hypotension, temperature monitoring, timely antibiotic redosing, intraoperative glucose evaluation and management, neuromuscular blockade documentation, ventilator management, and volatile anesthetic overuse. Results: Among 26 254 participants, 13 393 (51.0%) were female and 20 169 (76.8%) were White, with a median (IQR) age of 60 (47-69) years. There was no treatment effect on avoidance of hyperglycemia (7445 of 8676 patients [85.8%] in the intervention group vs 7559 of 8815 [85.8%] in the control group; rate ratio [RR], 1.00; 95% CI, 0.99-1.01) or hypothermia (7602 of 11 447 patients [66.4%] in the intervention group vs 7783 of 11 672 [66.7.%] in the control group; RR, 1.00; 95% CI, 0.97-1.02). Intraoperative glucose measurement was more common among patients with diabetes in the intervention group (RR, 1.07; 95% CI, 1.01-1.15), but other secondary outcomes were not significantly different. Conclusions and Relevance: In this randomized clinical trial, anesthesia care quality measures did not differ between groups, with high confidence in the findings. These results suggest that the intervention did not affect the targeted care practices. Further streamlining of clinical decision support and workflows may help the intraoperative telemedicine program achieve improvement in targeted clinical measures. Trial Registration: ClinicalTrials.gov Identifier: NCT02830126.


Asunto(s)
Hiperglucemia , Hipotermia , Adulto , Humanos , Femenino , Persona de Mediana Edad , Anciano , Masculino , Hipotermia/prevención & control , Hiperglucemia/prevención & control , Grupos Control , Centros Médicos Académicos , Glucosa
7.
BMJ Open Ophthalmol ; 8(1)2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-37278429

RESUMEN

OBJECTIVE: To study in a masked fashion whether an objective histological feature associated with keratoconus (KCN) occurs in donor corneas in eyes originally receiving a corneal graft for KCN. METHODS: Two ocular pathologists performed a retrospective masked histological analysis of slides from donor buttons recovered from 21 eyes with a history of KCN undergoing repeat penetrating keratoplasty (failed-PK-KCN), 11 eyes that underwent their first PK due to KCN (primary KCN), and 11 eyes without history of KCN which underwent PK for other conditions (failed-PK-non-KCN). Breaks/gaps in Bowman's layer served as the pathological feature indicative of recurrent KCN. RESULTS: Breaks in Bowman's layer were present in 18/21 (86%) of the failed-PK-KCN group, 10/11 (91%) of the primary KCN group, and in 3/11 (27%) of the failed-PK-non-KCN group. Pathological evidence suggests that the prevalence of breaks is significantly higher in grafted patients with a history of KCN than non-KCN controls (OR: 16.0, 95% CI 2.63 to 97.2, Fisher's exact test p=0.0018) with a conservative Bonferroni criterion of p <0.017 to account for multiple group comparisons. There was no statistically significant difference found between the failed-PK-KCN and primary KCN groups. CONCLUSIONS: This study provides histological evidence that breaks and gaps in Bowman's layer, consistent with those found in primary KCN, may develop within the donor tissue in eyes with a history of KCN.


Asunto(s)
Trasplante de Córnea , Queratocono , Humanos , Queratocono/cirugía , Estudios Retrospectivos , Córnea/cirugía , Trasplante de Córnea/efectos adversos , Queratoplastia Penetrante
8.
Am J Obstet Gynecol MFM ; 5(7): 100956, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37023986

RESUMEN

BACKGROUND: Preeclampsia is an obstetrical disorder, which complicates 3% to 6% of pregnancies and contributes to 21.6% of readmissions in the postpartum period. The optimal strategy for inpatient monitoring of blood pressures to minimize readmissions for postpartum patients with hypertensive disorders is not known. We hypothesized that extended monitoring of postpartum patients with hypertensive disorders of pregnancy for at least 36 hours after the last blood pressure that was ≥150/100 mm Hg would result in decreased readmission rates for preeclampsia with severe features compared with those who were not observed by these blood pressure goals. OBJECTIVE: This study aimed to evaluate whether extended inpatient monitoring of postpartum patients with hypertensive disorders of pregnancy for at least 36 hours after their last blood pressure that was ≥150/100 mm Hg would improve readmission rates for preeclampsia with severe features within 6 weeks of delivery. STUDY DESIGN: This was a retrospective cohort study in patients with a singleton pregnancy and a diagnosis of a hypertensive disorder of pregnancy at their delivery admission or at any point during pregnancy who delivered 1 year before and 1 year after the implementation of extended inpatient monitoring of postpartum hypertension. The primary outcome was readmission for preeclampsia with severe features within 6 weeks of delivery. The secondary outcomes were length of stay during first admission, number of readmissions for any indication, intensive care unit admission, postpartum day at readmission, median systolic blood pressure in the 24-hour period before discharge, median diastolic blood pressure in the 24-hour period before discharge, intravenous antihypertensive medication required during first admission, and intravenous antihypertensive medication required during second admission. Univariable analysis was performed for the association between baseline maternal characteristics and the primary outcome. Multivariable analysis was performed, adjusting for baseline maternal characteristic differences between exposure groups. RESULTS: A total of 567 patients met the inclusion criteria of which 248 patients delivered before and 319 delivered after the implementation of extended monitoring. For baseline characteristics, the extended monitoring group had a significantly higher proportion of patients who were non-Hispanic Black and Hispanic, more diagnoses of hypertensive disorders and/or diabetes mellitus at the time of admission for delivery, a difference in the distribution of hypertensive diagnoses at the time of discharge from the first admission, and fewer discharged patients from their first admission on labetalol than the preintervention group. In a univariable analysis of the primary outcome, there was a significantly increased risk of readmission for preeclampsia with severe features in the extended monitoring group (62.5% vs 96.2% of total readmissions; P=.004). In multivariable analysis, patients in the extended monitoring group were more likely to be readmitted for preeclampsia with severe features than patients in the preintervention group (adjusted odds ratio, 3.45; 95% confidence interval, 1.03-11.5; P=.044). CONCLUSION: Extended monitoring with a strict blood pressure goal of <150/<100 mm Hg did not decrease readmissions for preeclampsia with severe features in patients with a previous diagnosis of a hypertensive disorder of pregnancy.


Asunto(s)
Hipertensión Inducida en el Embarazo , Preeclampsia , Embarazo , Femenino , Humanos , Preeclampsia/diagnóstico , Preeclampsia/epidemiología , Preeclampsia/prevención & control , Hipertensión Inducida en el Embarazo/diagnóstico , Hipertensión Inducida en el Embarazo/epidemiología , Hipertensión Inducida en el Embarazo/prevención & control , Readmisión del Paciente , Antihipertensivos/uso terapéutico , Estudios Retrospectivos , Pacientes Internos , Periodo Posparto
9.
Hum Mol Genet ; 32(2): 204-217, 2023 01 06.
Artículo en Inglés | MEDLINE | ID: mdl-35943778

RESUMEN

EFEMP1 R345W is a dominant mutation causing Doyne honeycomb retinal dystrophy/malattia leventinese (DHRD/ML), a rare blinding disease with clinical pathology similar to age-related macular degeneration (AMD). Aged Efemp1  R345W/R345W knock-in mice (Efemp1ki/ki) develop microscopic deposits on the basal side of retinal pigment epithelial cells (RPE), an early feature in DHRD/ML and AMD. Here, we assessed the role of alternative complement pathway component factor B (FB) in the formation of these deposits. RNA-seq analysis of the posterior eyecups revealed increased unfolded protein response, decreased mitochondrial function in the neural retina (by 3 months of age) and increased inflammatory pathways in both neural retina and posterior eyecups (at 17 months of age) of Efemp1ki/ki mice compared with wild-type littermate controls. Proteomics analysis of eye lysates confirmed similar dysregulated pathways as detected by RNA-seq. Complement activation was increased in aged Efemp1ki/ki eyes with an approximately 2-fold elevation of complement breakdown products iC3b and Ba (P < 0.05). Deletion of the Cfb gene in female Efemp1ki/ki mice partially normalized the above dysregulated biological pathway changes and oral dosing of a small molecule FB inhibitor from 10 to 12 months of age reduced sub-RPE deposits by 65% (P = 0.029). In contrast, male Efemp1ki/ki mice had fewer sub-RPE deposits than age-matched females, no elevation of ocular complement activation and no effect of FB inhibition on sub-RPE deposits. The effects of FB deletion or inhibition on Efemp1ki/ki mice supports systemic inhibition of the alternative complement pathway as a potential treatment of dry AMD and DHRD/ML.


Asunto(s)
Degeneración Macular , Drusas del Disco Óptico , Masculino , Ratones , Femenino , Animales , Factor B del Complemento/genética , Degeneración Macular/genética , Degeneración Macular/patología , Drusas del Disco Óptico/patología , Retina/patología , Epitelio Pigmentado de la Retina/patología
10.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-998031

RESUMEN

Introduction@#Cancer patients are more susceptible to coronavirus disease-19 (COVID-19) infection because they are immunosuppressed by their disease or therapy, most of them have coexisting medical conditions, and they frequently visit hospitals for treatment and surveillance. @*Objective@#The objective of this study was to determine the prevalence of COVID-19 infection among gynecologic oncology patients receiving treatment in a COVID-19 referral hospital. @*Materials and Methods@#A descriptive, cross-sectional study involving 47 gynecologic cancer patients receiving treatment from June 2020 to December 2020 was performed. All patients underwent SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) swab test and symptom and exposure assessment before the start of cancer treatment. Patients with negative SARS-CoV-2 RT-PCR swab test results received their planned treatment, and a repeat swab test and triage assessment were done midtreatment and after treatment. @*Results@#Five (10.6%) patients had positive baseline SARS-CoV-2 RT-PCR swab results, but all proceeded with treatment after negative results were obtained. Only 1 (2.13%) patient had a positive SARS-CoV-2 RT-PCR swab test result at midtreatment. All patients had no COVID-19-associated symptoms and none of them tested positive for COVID-19 infection posttreatment. @*Conclusion@#The prevalence of COVID-19 infection among gynecologic cancer patients receiving cancer treatment is 2.13%. All patients who had positive SARS-CoV-2 RT-PCR swab test results at baseline or midtreatment were able to continue and complete treatment. There were no severe clinical events or mortalities among those affected with COVID-19 infection.


Asunto(s)
COVID-19
11.
Sci Adv ; 7(44): eabd8405, 2021 Oct 29.
Artículo en Inglés | MEDLINE | ID: mdl-34714682

RESUMEN

When considering safety standards for human exposure to radiofrequency (RF) and microwave energy, the dominant concerns pertain to a thermal effect. However, in the case of high-power pulsed RF/microwave energy, a rapid thermal expansion can lead to stress waves within the body. In this study, a computational model is used to estimate the temperature profile in the human brain resulting from exposure to various RF/microwave incident field parameters. The temperatures are subsequently used to simulate the resulting mechanical response of the brain. Our simulations show that, for certain extremely high-power microwave exposures (permissible by current safety standards), very high stresses may occur within the brain that may have implications for neuropathological effects. Although the required power densities are orders of magnitude larger than most real-world exposure conditions, they can be achieved with devices meant to emit high-power electromagnetic pulses in military and research applications.

12.
Br J Anaesth ; 127(3): 386-395, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34243940

RESUMEN

BACKGROUND: Intraoperative EEG suppression duration has been associated with postoperative delirium and mortality. In a clinical trial testing anaesthesia titration to avoid EEG suppression, the intervention did not decrease the incidence of postoperative delirium, but was associated with reduced 30-day mortality. The present study evaluated whether the EEG-guided anaesthesia intervention was also associated with reduced 1-yr mortality. METHODS: This manuscript reports 1 yr follow-up of subjects from a single-centre RCT, including a post hoc secondary outcome (1-yr mortality) in addition to pre-specified secondary outcomes. The trial included subjects aged 60 yr or older undergoing surgery with general anaesthesia between January 2015 and May 2018. Patients were randomised to receive EEG-guided anaesthesia or usual care. The previously reported primary outcome was postoperative delirium. The outcome of the current study was all-cause 1-yr mortality. RESULTS: Of the 1232 subjects enrolled, 614 subjects were randomised to EEG-guided anaesthesia and 618 subjects to usual care. One-year mortality was 57/591 (9.6%) in the guided group and 62/601 (10.3%) in the usual-care group. No significant difference in mortality was observed (adjusted absolute risk difference, -0.7%; 99.5% confidence interval, -5.8% to 4.3%; P=0.68). CONCLUSIONS: An EEG-guided anaesthesia intervention aiming to decrease duration of EEG suppression during surgery did not significantly decrease 1-yr mortality. These findings, in the context of other studies, do not provide supportive evidence for EEG-guided anaesthesia to prevent intermediate term postoperative death. CLINICAL TRIAL REGISTRATION: NCT02241655.


Asunto(s)
Anestesia/mortalidad , Electroencefalografía , Monitorización Neurofisiológica Intraoperatoria , Complicaciones Posoperatorias/mortalidad , Accidentes por Caídas , Anciano , Anestesia/efectos adversos , Monitores de Conciencia , Delirio/etiología , Delirio/mortalidad , Electroencefalografía/instrumentación , Femenino , Humanos , Monitorización Neurofisiológica Intraoperatoria/instrumentación , Masculino , Persona de Mediana Edad , Missouri , Complicaciones Cognitivas Postoperatorias/etiología , Complicaciones Cognitivas Postoperatorias/mortalidad , Complicaciones Posoperatorias/etiología , Valor Predictivo de las Pruebas , Calidad de Vida , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento
13.
Invest Ophthalmol Vis Sci ; 62(7): 26, 2021 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-34160562

RESUMEN

Purpose: Dysregulation of the alternative complement pathway is a major pathogenic mechanism in age-related macular degeneration. We investigated whether locally synthesized complement components contribute to AMD by profiling complement expression in postmortem eyes with and without AMD. Methods: AMD severity grade 1 to 4 was determined by analysis of postmortem acquired fundus images and hematoxylin and eosin stained histological sections. TaqMan (donor eyes n = 39) and RNAscope/in situ hybridization (n = 10) were performed to detect complement mRNA. Meso scale discovery assay and Western blot (n = 31) were used to measure complement protein levels. Results: The levels of complement mRNA and protein expression were approximately 15- to 100-fold (P < 0.0001-0.001) higher in macular retinal pigment epithelium (RPE)/choroid tissue than in neural retina, regardless of AMD grade status. Complement mRNA and protein levels were modestly elevated in vitreous and the macular neural retina in eyes with geographic atrophy (GA), but not in eyes with early or intermediate AMD, compared to normal eyes. Alternative and classical pathway complement mRNAs (C3, CFB, CFH, CFI, C1QA) identified by RNAscope were conspicuous in areas of atrophy; in those areas C3 mRNA was observed in a subset of IBA1+ microglia or macrophages. Conclusions: We verified that RPE/choroid contains most ocular complement; thus RPE/choroid rather than the neural retina or vitreous is likely to be the key site for complement inhibition to treat GA or earlier stage of the disease. Outer retinal local production of complement mRNAs along with evidence of increased complement activation is a feature of GA.


Asunto(s)
Coroides , Activación de Complemento , Proteínas del Sistema Complemento/genética , Degeneración Macular , Retina , Epitelio Pigmentado de la Retina , Anciano , Autopsia/métodos , Coroides/metabolismo , Coroides/patología , Vía Alternativa del Complemento , Femenino , Perfilación de la Expresión Génica/métodos , Atrofia Geográfica/patología , Humanos , Degeneración Macular/metabolismo , Degeneración Macular/patología , Masculino , ARN Mensajero/análisis , Retina/metabolismo , Retina/patología , Epitelio Pigmentado de la Retina/metabolismo , Epitelio Pigmentado de la Retina/patología
14.
Am J Ophthalmol ; 226: 191-200, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33529584

RESUMEN

PURPOSE: To find immunohistochemical markers that distinguish adenocarcinoma of the nonpigmented ciliary epithelium (NPCE) from metastatic carcinoma, especially metastatic renal cell carcinoma. DESIGN: Retrospective case series. METHODS: Three cases of adenocarcinoma of the NPCE were examined histologically with hematoxylin-eosin stain and immunohistochemical stains including vimentin, AE1/AE3, Cam 5.2, CK7, PAX2, PAX8, AMACR, and CAIX. We also reviewed previously reported cases of this tumor. RESULTS: We found that the immunohistochemical profile of adenocarcinoma of the NPCE can overlap with renal cell carcinoma. Both tumors can express vimentin, cytokeratin AE1/AE3, Cam 5.2, PAX2, PAX8, and AMACR. One of the adenocarcinomas of the NPCE in our series also expressed CD10 and the renal cell carcinoma marker (RCC Ma). Carbonic anhydrase IX (CAIX) was not detected in any of the 3 tumors. CONCLUSIONS: Adenocarcinomas arising in phthisic eyes can be diagnostically challenging. We have found it particularly difficult to distinguish adenocarcinoma of the NPCE from metastatic carcinoma, especially metastatic clear cell renal cell carcinoma and papillary renal cell carcinoma. Because of the immunophenotypic overlap, most patients will require systemic workup including imaging of the kidneys to be certain of the diagnosis.


Asunto(s)
Adenocarcinoma/diagnóstico , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Renales/diagnóstico , Cuerpo Ciliar/patología , Neoplasias Renales/diagnóstico , Proteínas de Neoplasias/metabolismo , Neoplasias de la Úvea/diagnóstico , Adenocarcinoma/metabolismo , Adulto , Anciano , Carcinoma de Células Renales/metabolismo , Cuerpo Ciliar/metabolismo , Femenino , Humanos , Inmunohistoquímica , Neoplasias Renales/metabolismo , Masculino , Persona de Mediana Edad , Epitelio Pigmentado Ocular/metabolismo , Epitelio Pigmentado Ocular/patología , Estudios Retrospectivos , Neoplasias de la Úvea/metabolismo
15.
Toxicol Appl Pharmacol ; 416: 115466, 2021 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-33631229

RESUMEN

Soman, an organophosphorus (OP) compound, disrupts nervous system function through inactivation of acetylcholinesterase (AChE), the enzyme that breaks down acetylcholine at synapses. Left untreated, a state of prolonged seizure activity (status epilepticus, SE) is induced, causing widespread neuronal damage and associated cognitive and behavioral impairments. Previous research demonstrated that therapeutic stimulation of A1 adenosine receptors (A1ARs) can prevent or terminate soman-induced seizure. This study examined the ability of three potent A1AR agonists to provide neuroprotection and, ultimately, prevent observable cognitive and behavioral deficits following exposure to soman. Sprague Dawley rats were challenged with a seizure-inducing dose of soman (1.2 x LD50) and treated 1 min later with one of the following A1AR agonists: (6)-Cyclopentyladenosine (CPA), 2-Chloro-N6-cyclopentyladenosine (CCPA) or N-bicyclo(2.2.1)hept-2-yl-5'-chloro-5'-deoxyadenosine (cdENBA). An active avoidance shuttle box task was used to evaluate locomotor responses to aversive stimuli at 3, 7 and 14 days post-exposure. Animals treated with CPA, CCPA or cdENBA demonstrated a higher number of avoidance responses and a faster reaction to the aversive stimulus than the soman/saline control group across all three sessions. Findings suggest that A1AR agonism is a promising neuroprotective countermeasure, capable of preventing the long-term deficits in learning and memory that are characteristic of soman intoxication.


Asunto(s)
Agonistas del Receptor de Adenosina A1/farmacología , Anticonvulsivantes/farmacología , Encéfalo/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Intoxicación por Organofosfatos/prevención & control , Receptor de Adenosina A1/efectos de los fármacos , Convulsiones/prevención & control , Soman , Adenosina/análogos & derivados , Adenosina/farmacología , Animales , Conducta Animal/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología , Desoxiadenosinas/farmacología , Modelos Animales de Enfermedad , Masculino , Intoxicación por Organofosfatos/etiología , Intoxicación por Organofosfatos/metabolismo , Intoxicación por Organofosfatos/fisiopatología , Ratas Sprague-Dawley , Receptor de Adenosina A1/metabolismo , Convulsiones/inducido químicamente , Convulsiones/metabolismo , Convulsiones/patología
16.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-964827

RESUMEN

@#Endometrial cancer is frequently diagnosed at an early stage and exhibits a good prognosis. However, 10%–15% of tumors recur usually within 3 years. Common sites of recurrence are the vaginal vault and pelvis. Only a number of case reports exist for tumor recurrence in a previous incision site. We present a case of a 71‑year‑old Filipino woman, a diagnosed case of Endometrial Adenocarcinoma Stage III A, FIGO Grade 1, who underwent surgical management, chemotherapy, and radiation therapy 9 years prior, presenting with an abdominal mass at the inferior aspect of the previous surgical scar with the foul‑smelling discharge of 1‑year duration. Physical examination revealed a 6 cm × 4 cm, friable, movable, nontender abdominal mass, with associated edema of the mons pubis. Surgical resection showed that the mass was confined to the abdominal wall, with no extension beneath the fascia and no evidence of tumor in the pelvic and abdominal cavity. Histological examination revealed a moderately differentiated adenocarcinoma in the abdominal wall, confirming tumor recurrence in an atypical location, probably arising from the previous incision site.


Asunto(s)
Neoplasias Endometriales , Recurrencia
17.
F1000Res ; 9: 1261, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33214879

RESUMEN

Introduction: The post-anesthesia care unit (PACU) is a clinical area designated for patients recovering from invasive procedures. There are typically several geographically dispersed PACUs within hospitals. Patients in the PACU can be unstable and at risk for complications. However, clinician coverage and patient monitoring in PACUs is not well regulated and might be sub-optimal. We hypothesize that a telemedicine center for the PACU can improve key PACU functions. Objectives: The objective of this study is to demonstrate the potential utility and acceptability of a telemedicine center to complement the key functions of the PACU. These include participation in hand-off activities to and from the PACU, detection of physiological derangements, identification of symptoms requiring treatment, recognition of situations requiring emergency medical intervention, and determination of patient readiness for PACU discharge. Methods and analysis: This will be a single center prospective before-and-after proof-of-concept study. Adults (18 years and older) undergoing elective surgery and recovering in two selected PACU bays will be enrolled. During the initial three-month observation phase, clinicians in the telemedicine center will not communicate with clinicians in the PACU, unless there is a specific patient safety concern. During the subsequent three-month interaction phase, clinicians in the telemedicine center will provide structured decision support to PACU clinicians. The primary outcome will be time to PACU discharge readiness determination in the two study phases. The attitudes of key stakeholders towards the telemedicine center will be assessed. Other outcomes will include detection of physiological derangements, complications, adverse symptoms requiring treatments, and emergencies requiring medical intervention. Registration: This trial is registered on clinicaltrials.gov, NCT04020887 (16 th July 2019).


Asunto(s)
Anestesia , Telemedicina , Adulto , Humanos , Monitoreo Fisiológico , Estudios Observacionales como Asunto , Alta del Paciente , Estudios Prospectivos
18.
Curr Pharm Teach Learn ; 12(12): 1470-1476, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33092777

RESUMEN

BACKGROUND AND PURPOSE: Use of problem-based learning (PBL) in health professions education has limited data supporting improved exam performance and confidence in problem solving, primarily within courses converted to a PBL format. This study aimed to demonstrate a similar benefit in simultaneous and subsequent required, non-PBL courses that involved critical thinking. EDUCATIONAL ACTIVITY AND SETTING: This retrospective cohort study included students who were enrolled in the pharmacotherapeutics and case studies/laboratory course sequences in the second and third professional (P3) years. We compared performance across both course sequences of students who took a PBL elective course in the fall of the P3 year (PBL students) and students who did not take the elective course (non-PBL students). FINDINGS: There was a statistically significant difference favoring PBL students in performance in both the therapeutics and case/lab courses offered simultaneously with the PBL elective. There was no significant difference noted between PBL and non-PBL student performance in the subsequent therapeutics and case/lab courses; however, results within individual cohorts differed strikingly from the aggregate analysis. Performance in the PBL elective had no impact on the outcomes of the study. SUMMARY: This study demonstrated an overall benefit for students who participated in a PBL course on performance in simultaneous, critical thinking courses that did not incorporate PBL. However, the aggregate did not show a difference in performance in subsequent critical thinking, non-PBL courses. Further studies are needed to elucidate the true benefit of the PBL approach in other non-PBL courses that require advanced clinical reasoning.


Asunto(s)
Aprendizaje Basado en Problemas , Pensamiento , Humanos , Solución de Problemas , Estudios Retrospectivos , Estudiantes
19.
Semin Ophthalmol ; 35(3): 174-181, 2020 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-32507011

RESUMEN

PURPOSE: To explore the value of molecular technologies in the pathologic evaluation, diagnosis, and treatment of retinoblastoma and uveal melanoma. METHODS: Review of the peer-reviewed literature on the molecular pathology of primary intraocular tumors. CONCLUSION: Molecular tests are playing an increasingly important role in the diagnosis of intraocular tumors. They provide information valuable for diagnosis, prognosis, screening regimens, genetic counselling, and treatment. These technologies are becoming easier, faster, and with higher sensitivity and accuracy.


Asunto(s)
Melanoma/genética , Biología Molecular , Neoplasias de la Retina/genética , Retinoblastoma/genética , Neoplasias de la Úvea/genética , Diagnóstico Diferencial , Asesoramiento Genético , Pruebas Genéticas , Humanos , Pronóstico
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