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Different categories of extracellular vesicles (EVs) are identified based on their origin and formation processes. Among these, exosomes (EXOs) originate from endosomal compartments merging with the plasma membrane, forming small lipid vesicles that transport a range of molecular cargo such as nucleic acids, proteins, and lipids. The composition of EXOs varies depending on their cellular source, encompassing various cell types, including neutrophils, dendritic cells, and even tumor cells. Remarkably, EXOs possess inherent stability, low immunogenicity, and compatibility, making them efficient nano vectors for drug delivery. Imaging techniques like bioluminescence, fluorescence, and nuclear imaging are crucial in non-invasively tracking EXOs within living organisms. This process requires the attachment of radionuclides to the EXO's structure without altering its essential characteristics. Real-time imaging of EXOs is vital for their clinical application, and recent advancements in labeling and tracking methodologies provide insights into biodistribution, functionality, and potential pathways for EXO-mediated drug delivery. This review presents updated progress in the diverse applications of EXOs in targeted imaging across various modalities, where they function as contrast agents facilitating tissue visualization and disease tracking. Consequently, EXOs emerge as promising entities in medical diagnostics and imaging.
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INTRODUCTION: Our goal was to compare the perceived readiness of graduating urologic residents and fellows to program directors (PDs) in U.S.-based postgraduate training programs. Additionally, we set out to assess the impact of COVID-19 on postgraduation plans to pursue fellowship training. METHODS: Graduating residents, fellows, and PDs of accredited residency/fellowship programs in the U.S. were surveyed. The ranked preparedness of trainees to perform common urologic procedures was measured using a Likert scale from 1 (not comfortable) to 5 (fully proficient). The impact of COVID-19 was measured using a three-point Likert scale. Chi-squared and Kruskal-Wallis analyses were used to compare the groups. RESULTS: From 93 responders, 21 were residents, 19 were fellows, 24 were residency PDs, and 29 were fellowship PDs. The median levels of comfort for trans-urethral resection of the prostate, hydrocelectomy, vasectomy, and urethral sling were at or above (≥3) moderate for both PDs and trainees. PDs were more likely to report underperformance for hypospadias repair (60% vs. 39%), penile prosthesis implantation (39% vs. 26%), and orthotopic neobladder formation (57% vs. 18%) than the trainees. Fifty-three (57.0%) of the surveyors felt that COVID-19 did not impact the trainees' comfort in performing general urologic procedures. COVID-19 influenced trainees' decision to pursue a fellowship or opt to practice as general urologists (p=0.002). CONCLUSIONS: Our study suggests there may be a self-reported discrepancy between graduating trainees and their PDs regarding trainees' comfort levels performing general urologic procedures.
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OBJECTIVE: Our study aims to examine the role of multi-disciplinary surgical pause committees (MDSPC) in perioperative planning to reduce adverse postoperative events and mortality rates. SUMMARY BACKGROUND DATA: Frail patients could benefit from preoperative MDSPCs when utilizing risk-benefit ratios for the proposed surgical plan. We examined whether MDSPCs improved clinical outcomes by developing individualized care plans and stratifying patients based on their level of frailty and ability to overcome external stressors. METHODS: We retrospectively collected patient information after MDSPC evaluation, at our medical center for 12 years since 2011. Patient's frailty risk assessment index (RAI) scores were calculated, and survival status was updated. MDSPCs plans were put into the following categories: proceed with the planned surgery (G1), proceed after medical optimization (G2), reduce invasiveness of surgery or anesthesia plan (G3), or adopt a non-surgical approach (G4). Chi-square and independent t-tests were used for categorical and numerical data, respectively. Survival analysis for 30-day (primary endpoint), one-year, and overall mortality rates used Kaplan-Meier. The alpha was set at 0.05. RESULTS: Clinical information was accessed from 12 women and 382 men. The average age was 71±11 years. 87.3% of planned surgical operations were stratified as ASA class III and IV. RAI scores were 36.4±9.6 (G1), similar to 37.4±10.8 (G2) but lower than 41.4±9.3 (G3) and 44.2±9.7 (G4) (P<0.001). Average survival duration was 35 months (G1), 35 months (G2), both significantly longer than 20 months (G3) and 18 months (G4) (P<0.001). CONCLUSION: Medical optimization improved overall survival and reduced death within 30 days and one year to be comparable to G1. Additionally, reducing the surgical invasiveness only improved survival advantage for six months, after which it was comparable to those in G4 with the worst outcome. RAI scoring is an excellent tool to predict the outcome of surgery, and it was used successfully in critically ill patients.
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BACKGROUND: Left ventricular systolic dysfunction in patients with severe aortic stenosis (AS) may result in low transvalvular gradients and underestimation of AS severity. A low-flow state may occur with reduced LVEF. Little is known about the implications of low compared to normal flow in patients with reduced LVEF undergoing transcatheter aortic valve replacement (TAVR). OBJECTIVES: We compared survival rates with degree of flow across stenosed aortic valves and left ventricular dysfunction. We hypothesized that the stroke volume index (SVI) offers essential information regarding survival following TAVR. METHODS: We retrospectively reviewed patients with LVEF <50 % undergoing TAVR at the Gates Vascular Institute in Buffalo, New York, from 2012 to 2017. We performed Receiver Operator Characteristics to examine the value of SVI in predicting the postoperative outcome of patients. Kaplan-Meier and Cox regression analyses were used to investigate the effect of a low-flow state on five-year survival in patients with systolic dysfunction undergoing TAVR. RESULTS: Five-year survival following TAVR was decreased in patients with low-flow AS (SVI <35 mL/m2) compared to patients with normal flow. Seventy-four percent (n = 50) of patients with low-flow compared to 43 % (n = 22) of patients with normal flow were deceased five years post-TAVR (p ≤0.001). ROC curve indicated SVI to be a clinical predictor of five year survival (AUC 0.732, 95 % CI: 0.641-0.823, p < 0.001). CONCLUSION: Patients with systolic dysfunction and low transvalvular flow AS had increased mortality five years following TAVR. These findings highlight a better prognosis in patients with normal flow and LV systolic dysfunction. CONDENSED ABSTRACT: Low-flow aortic stenosis can occur with reduced left ventricular function. We compared survival rates of patients with known reduced left ventricular function in low-flow and normal flow aortic stenosis. This retrospective single-center study examined mortality rates following transcatheter aortic valve replacement. The mean gradient was not a predictor of mortality. This study shows patients with low-flow aortic stenosis have decreased five-year survival following valve replacement.
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INTRODUCTION: Our goal was to compare the perceived readiness of graduating urologic residents and fellows to program directors (PDs) in U.S.-based postgraduate training programs. Additionally, we set out to assess the impact of COVID-19 on postgraduation plans to pursue fellowship training. METHODS: Graduating residents, fellows, and PDs of accredited residency/fellowship programs in the U.S. were surveyed. The ranked preparedness of trainees to perform common urologic procedures was measured using a Likert scale from 1 (not comfortable) to 5 (fully proficient). The impact of COVID-19 was measured using a three-point Likert scale. Chi-squared and Kruskal-Wallis analyses were used to compare the groups. RESULTS: From 93 responders, 21 were residents, 19 were fellows, 24 were residency PDs, and 29 were fellowship PDs. The median levels of comfort for transurethral resection of the prostate, hydrocelectomy, vasectomy, and urethral sling were at or above (≥3) moderate for both PDs and trainees. PDs were more likely to report underperformance for hypospadias repair (60% vs. 39%), penile prosthesis implantation (39% vs. 26%), and orthotopic neobladder formation (57% vs. 18%) than the trainees. Fifty-three (57.0%) of the surveyors felt that COVID-19 did not impact the trainees' comfort in performing general urologic procedures. COVID-19 influenced trainees' decision to pursue a fellowship or opt to practice as general urologists (p=0.002). CONCLUSIONS: Our study suggests there may be a self-reported discrepancy between graduating trainees and their PDs regarding trainees' comfort levels performing general urologic procedures.
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BACKGROUND: Prone positioning (PP) is a low-cost method with minimal risk to the patient that improves the oxygenation of patients with acute hypoxic respiratory failure (AHRF) due to COVID-19 pneumonia, thereby reducing their need for tracheal intubation (TI) and transferring to the intensive care unit (ICU). We aimed to overview the results of all previous systematic reviews and meta-analyses to examine the net effect of PP on oxygenation, the rate of TI and mortality in COVID-19 patients. METHODS: We searched PubMed, Scopus, Web of Science, Google Scholar, and Cochrane Library databases from December 2019 through 2022 without publication language restriction for systematic reviews and meta-analysis studies on PP vs. supine position (SP) in conscious patients with hypoxic respiratory failure COVID-19. After study selection, data were extracted from published meta-analyses and pooled by comprehensive meta-analysis (CMA) software version 2.2.064 to achieve effect sizes. They were analyzed for TI and mortality rates dichotomous variables, and the results were shown as pooled odds ratios (OR) with a 95% confidence interval (CI). Continuous variables such as oxygenation indices (PaO2/FiO2 and SpO2) were also analyzed, and the data were shown as mean differences (MD) with lower and upper CI. The level of statistical significance was set at p ≤ 0.05. RESULTS: Twelve systematic reviews and meta-analyses with 19,651 patients and six systematic reviews with 2,911 patients were included in this Review of Reviews (total: 22,562). PP treatment significantly reduced the rate of TI (OR = 0.639, %95 CI (0.492, 0.829); P-value = 0.001) and decreased mortality (OR = 0.363, %95 CI (0.240, 0.549), P-value < 0.001). There was no difference in PaO2/FiO2 (MD = 3.591[- 40.881, 48.062]; P-value = 0.874) and SpO2 percent (MD = 1.641[- 4.441, 7.723]; P-value = 0.597). CONCLUSION: Prone positioning can be recommended in conscious ICU patients with COVID-19 pneumonia to reduce mortality and intubation. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number: CRD42022326951. Registered 25 April 2022.
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COVID-19 , Síndrome de Dificultad Respiratoria , Insuficiencia Respiratoria , Humanos , COVID-19/terapia , Hipoxia , Intubación Intratraqueal , Posición Prona , Síndrome de Dificultad Respiratoria/terapia , Insuficiencia Respiratoria/terapia , Revisiones Sistemáticas como Asunto , VigiliaRESUMEN
Introduction: Volatile anesthetics offer protection when administered throughout an ischemic injury. We examined how volatile anesthetics modulate the cardiac myocytic injury associated with hydrogen peroxide. Methods: Forty-eight Long-Evans rats were divided into four groups depending on the treatment: none (CONT), Glibenclamide (GLB); Sevoflurane (SEV); or GLB+SEV. Each group was further divided into two, one of which was exposed to hydrogen peroxide (H2O2). Oral GLB was administered 48 hours before myocardial isolation. All rats were anesthetized by intraperitoneal injection of Ketamine, and the hearts were harvested after heparinization. Cardiomyocytes were isolated using a combination of mechanical mincing and enzymatic digestion. After isolation, the aliquots of cells were exposed to H2O2 and FeSO4 for 30 minutes. The cell suspensions were then bubbled for 10 minutes with 100% oxygen and 1.5% SEV if appropriate. Apoptosis was detected by fluorescein-bound annexin-V (ANX-V), necrosis by propidium iodide, and ELISA assessed caspase-3 activity in all groups. Results: There was an increase in apoptosis, necrosis, and caspase-3 activity in the cells following exposure to hydrogen peroxide. SEV reduced the rate of cell necrosis and apoptosis. Pretreatment with GLB did not alter the effects of SEV. Similarly, caspase-3 activity did not change with GLB, although SEV administration reduced this enzymatic activity in response to hydrogen peroxide. Conclusion: In this oxidant injury model, we demonstrated that incubating isolated cardiomyocytes with SEV profoundly diminished H2O2-induced apoptotic and necrotic cells compared to their CONTs. These results support the hypothesis that KATP channels are not the sole mediators associated with anesthetic preconditioning.
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Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was the main pathogen in the COVID-19 pandemic. This viral infection has been associated with several respiratory and non-respiratory complications contributing to a higher mortality rate, especially in patients with underlying heart diseases worldwide. Once considered a respiratory tract disease, it is now well-known that COVID-19 patients may experience a wide range of cardiac manifestations. Because of its remarkable direct and indirect effects on the cardiovascular system, herein, we examined the published literature that studied the hypothetical mechanisms of injury, manifestations, and diagnostic modalities, including changes in molecular biomarkers with a predictive value in the prognostication of the disease, as well as emerging evidence regarding the long-term cardiac complications of the disease.
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BACKGROUND: Intrathecal opioids have long been used as analgesia for intractable cancer pain or as part of spinal anesthesia during obstetric operations. More recently, they have been used preoperatively as a pain management adjuvant for open cardiac and thoracic procedures. OBJECTIVE: This study aims to analyze the impact of administering intrathecal opioids before cardiac and thoracic surgeries on postoperative pain and mechanical ventilation. STUDY DESIGN: Systematic review and meta-analysis. SETTING: University, School of Medicine, and several university-affiliated hospitals. METHODS: Five outcomes were studied, including the primary outcome of time to extubation, secondary outcomes of analgesia requirements at 24 and 48 hours, resting pain scores at 1 and 24 hours post-extubation, ICU length of stay in hours, and hospital length of stay in days. A search of multiple databases provided 28 studies reporting 4,000 total patients. Outcomes were measured using continuous mean difference with a 95% confidence interval, and the studies were examined for heterogeneity and sensitivity analysis. RESULTS: The primary outcome analysis suggested that time to extubation was 42 minutes shorter in the intrathecal opioid group (ranging from 82 to 1 minute, P = 0.04). There was also a decrease in postoperative analgesia requirements at both 24 hours (mean difference (MD) = -8.95 mg morphine equivalent doses (MED) [-9.4, -8.5], P < 0.001) and 48 hours (MD = -17.7 mg MED [-23.1, -12.4], P < 0.001) with I2 of 94% and 85% respectively, an improvement of pain scores at both 1 hour (MD = -2.24 [-3.16, -1.32], P < 0.001) and 24-hours (MD = -1.64 [-2.48, -0.80], P =< 0.001) I2 of 94% and 85%, no change in both ICU length of stay (MD = -0.27 hours [-0.55, 0.01], P = 0.06) I2 = 77% and hospital length of stay (MD = -0.30 days [-0.66, 0.06], P = 0.11) I2 = 32%. LIMITATIONS: The major limitation of this meta-analysis was the inconsistent dosages of intrathecal opioids utilized. Some used the same dose for each patient, while other studies used weight-based doses. The differences in the outcomes observed may then be a result of the different amounts of opioids administered rather than the technique itself. Another limitation was the inconsistent timing of reports for pain scores and postoperative analgesic requirements. Further studies were analyzed at the 2 time periods for both secondary outcomes, making it difficult to attribute the 2 effects solely to the intervention. CONCLUSIONS: We conclude that preoperative injection of intrathecal opioids is significantly associated with decreased time to extubation, decreased postoperative analgesia requirement, and improved pain scores. In controlled conditions with adequate staff education, this method of analgesia may make it possible to extubate the patients after the surgery in the operating room and fast-track their discharge from the hospital.
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Analgésicos Opioides , Morfina , Humanos , Inyecciones Espinales , Morfina/uso terapéutico , Puente de Arteria Coronaria , Dolor Postoperatorio/tratamiento farmacológico , Resultado del TratamientoRESUMEN
PURPOSE: To compare the efficacy of phakic intra-ocular lenses in isolation or in combination with corneal crosslinking (CXL) and/or intra-stromal corneal ring segments (ICRS) in keratoconus. METHODS: Data extracted from the publications meeting the selection. The outcome parameters included mean pre- and post-operative uncorrected distance visual acuity, corrected distance visual acuity (CDVA), sphere and cylinder of refraction and complications. Available data analyzed with Cochrane Review Manager. RESULTS: A total of 23 studies including 464 eyes were included. All the parameters showed significant improvement in all subgroups other than CDVA in ACPIOL + CXL subgroup and cylinder in PIOL + CXL subgroups. There was not a significant difference between PCPIOL and ACPIOL in the outcomes, exception was more improvement of CDVA in "ACPIOL only" than" PCPIOL only" subgroup. CONCLUSION: Both PCPIOLs and ACPIOLs are comparably safe and efficient options in management of KCN and their efficacy significantly improves when combined with CXL/ICRS.
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Queratocono , Lentes Intraoculares Fáquicas , Humanos , Fármacos Fotosensibilizantes/uso terapéutico , Queratocono/tratamiento farmacológico , Queratocono/cirugía , Riboflavina/uso terapéutico , Colágeno/farmacología , Colágeno/uso terapéutico , Topografía de la Córnea , Reactivos de Enlaces Cruzados/uso terapéutico , Sustancia Propia/cirugíaRESUMEN
Cell therapy has reached significant milestones in various life-threatening diseases, including cancer. Cell therapy using fluorescent and radiolabeled chimeric antigen receptor (CAR)-T cell is a successful strategy for diagnosing or treating malignancies. Since cell therapy approaches have different results in cancers, the success of hematological cancers has yet to transfer to solid tumor therapy, leading to more casualties. Therefore, there are many areas for improvement in the cell therapy platform. Understanding the therapeutic barriers associated with solid cancers through cell tracking and molecular imaging may provide a platform for effectively delivering CAR-T cells into solid tumors. This review describes CAR-T cells' role in treating solid and non-solid tumors and recent advances. Furthermore, we discuss the main obstacles, mechanism of action, novel strategies and solutions to overcome the challenges from molecular imaging and cell tracking perspectives.
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Neoplasias , Receptores Quiméricos de Antígenos , Humanos , Inmunoterapia Adoptiva/métodos , Medicina de Precisión , Neoplasias/patología , Linfocitos T , Microambiente TumoralRESUMEN
The current study aims to investigate the relationship betweSen serum IL-17 (IL-17) levels and systemic lupus erythematosus disease activity index (SLE-DAEI) in systemic lupus erythematosus (SLE) patients. In this case-control study, 36 patients with SLE and 40 healthy individuals matched for age and sex were included as the control group. The study measured serum IL-17 in both groups. The correlation between serum IL-17 with disease activity (as per SLE-DAI) and organ involvement in SLE patients. The case group in this study consisted of 4 males and 32 females with a mean age of 35 (17-54) years old, and the control group included six males and 34 females with a mean age of 37 (25-53) years old (p = .35). Serum IL-17 was higher in the cases than in the controls (536 pg/mL vs. 110 pg/mL; p < .001). There was a positive correlation between the serum levels of IL-17 and disease activity index (p < .001, rho = 0.93) among cases. Additionally, the serum levels of IL-17 were higher in patients with renal (p = .003) or central nervous system involvement (p < .001) than in patients without such involvement. Serum Il-17 is associated with SLE, and its serum levels correlate positively with the disease activity and renal and nervous system involvement.
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Interleucina-17 , Lupus Eritematoso Sistémico , Masculino , Femenino , Humanos , Adulto , Adolescente , Adulto Joven , Persona de Mediana Edad , Estudios de Casos y Controles , Lupus Eritematoso Sistémico/complicaciones , Riñón , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVES: The Doppler profile that quantifies the degree of aortic stenosis is essential, as an inaccurate measurement can alter the surgical plan. The authors aimed to examine the level of agreement between the contrast and noncontrast methods of aortic valve sizing during intraoperative transesophageal echocardiography (TEE). SETTING: At a tertiary hospital. PARTICIPANTS: A total of 30 patients undergoing surgical aortic valve replacement for a stenotic valve. INTERVENTIONS: Perflutren lipid microsphere contrast injection. MEASUREMENTS AND MAIN RESULTS: The authors reviewed Doppler studies of 30 consecutive patients undergoing aortic valve replacement in whom a contrast agent was given (perflutren lipid microsphere). They measured the peak and/or mean aortic valve gradients and velocity time integral readings through the left ventricular outflow tract (LVOT), and the aortic valve before and after administering the contrast agent. The aortic valve area was then calculated using both methods. Paired t tests and Bland-Altman analyses were used to examine the bias and the level of agreement between the 2 processes. By not using a contrast agent, the aortic valve area was overestimated by 0.26 cm2 compared to those measured by transthoracic echocardiography (TTE) (p < 0.001). Using a contrast agent, TEE measurements were comparable to those obtained by TTE. Moreover, the peak and mean aortic valve gradients were underestimated by 19 and 11 mmHg, respectively (p value <0.001). Adding contrast did not affect the pulse-wave Doppler readings of the V1 velocity of the LVOT. CONCLUSION: This discrepancy is significant and could affect the decision to replace the aortic valve. When evaluating the aortic valve with TEE, the authors recommend using a contrast agent to improve the Doppler profile and to obtain a more accurate measurement of the aortic valve area.
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Estenosis de la Válvula Aórtica , Válvula Aórtica , Humanos , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Ecocardiografía Transesofágica/métodos , Medios de Contraste , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/cirugía , LípidosRESUMEN
BACKGROUND: As transcatheter aortic valve replacement (TAVR) procedures become more widely available, there is a growing need to monitor and evaluate postoperative outcomes accurately. The energy loss index (ELI) of the ascending aorta has been commonly used to examine the agreement between the echocardiographic and Gorlin measurement of the aortic valve area. OBJECTIVES: This project aims to demonstrate a link between ELI values and mortality following implanted TAVR valves and determine an ELI cutoff value associated with post-TAVR events. METHOD: We retrospectively reviewed patients undergoing TAVR from 2012 to 2017. We calculated ELI values for patients immediately postoperative after a TAVR procedure. Using Receiver-Operator Characteristic and Cox Regression analyses, we identified a cutoff value to distinguish between "High ELI" (≥ 1.34) and "Low ELI" (< 1.34) patients. RESULTS: This study showed low ELI (hazard ratio, 2.30; 95% confidence interval 1.57-3.36, p < .001) as representative of patients with a high risk of mortality post-TAVR. Additionally, post-TAVR, ejection fraction increased by 3.6% (p < .001), and the aortic valve effective orifice area increased by 1.41 cm squared (p < .001) while the mean transvalvular gradient decreased by 32.8 mmHg (p < .001) and the peak transvalvular gradient decreased by 49.0 mmHg (p < .001). CONCLUSION: ELI is an additional prognostic factor that should be considered during risk assessment before TAVR. This study shows that patients with Low ELI had decreased cumulative survival post-TAVR. These patients almost had a fivefold increased risk of death following TAVR.
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Estenosis de la Válvula Aórtica , Reemplazo de la Válvula Aórtica Transcatéter , Humanos , Reemplazo de la Válvula Aórtica Transcatéter/métodos , Estudios de Seguimiento , Estenosis de la Válvula Aórtica/etiología , Estudios Retrospectivos , Resultado del Tratamiento , Válvula Aórtica/cirugía , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
AIMS: To investigate the role of vitamin D2 on the resolution of ST-segment elevation (STE) after a primary percutaneous coronary intervention (PCI), as serum levels of vitamin D have been associated with the severity of coronary artery disease. METHODS AND RESULTS: All patients who underwent PCI for STEMI were screened for enrolment. Vitamin D2 levels were measured on admission along with other biochemical and haematologic assays. The electrocardiography (ECG) was recorded upon arrival and 60 min after the completion of PCI. The primary endpoint of the study was a ≥ 50% resolution of ST-segment amplitude (+STR) when compared to the initial ECG. A logistic regression multivariate analysis was performed to examine the association of STR with all confounding variables, including the admission levels of vitamin D. Receiver-operator characteristics analysis was used to determine the cut-off value of vitamin D that was predictive of STR. Although there was no difference in STR based on standard classification of vitamin D sufficiency, critically low levels of vitamin D (<7.5 ng/mL) were significantly associated with the absence of STR after PCI (AUC was 0.65 ± 0.07; p < 0.001). Critical vitamin D deficiency was a moderate predictor of STR in these patients, with a sensitivity of 86% and specificity of 54%. CONCLUSION: We concluded that although levels below ten ng/mL were generally accepted as vitamin D deficiency, only critically low levels of this vitamin (<7.5 ng/dL) reliably predicted the resolution of ST-segment after a primary PCI for patients with STEMI.
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Infarto del Miocardio , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Deficiencia de Vitamina D , Humanos , Intervención Coronaria Percutánea/efectos adversos , Infarto del Miocardio con Elevación del ST/diagnóstico , Infarto del Miocardio con Elevación del ST/cirugía , Vitamina D , Resultado del Tratamiento , Angiografía Coronaria , Arritmias Cardíacas , Vitaminas , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/diagnóstico , Ergocalciferoles , Electrocardiografía/métodosRESUMEN
OBJECTIVES: Management of patients undergoing coronary artery bypass grafting (CABG) with obstructive disease of the carotid arteries is still a matter of debate. We compared the results of staged carotid artery stenting (CAS) before CABG in patients with carotid lesions. MATERIALS AND METHOD: Patients with significant carotid artery disease who were deemed to simultaneously suffer from an obstructive coronary artery disease requiring CABG from 2008 to 2018 were screened and enrolled in this study. We performed a staged CAS in cases with ≥60% stenosis and neurological symptoms or asymptomatic patients with ≥80% carotid artery stenosis. Patients with bilateral carotid lesions received sequential CAS within three weeks. Six weeks after the CAS procedure, all patients underwent CABG. RESULTS: A total of 142 patients were included. Eighty-five of these had neurological symptoms, while the remaining 40% were asymptomatic. Thirty-one patients underwent sequential CAS for bilateral lesions. The cerebrovascular event (CVE) following CAS (3 patients) and CABG (3 patients) was 4.2%. There was only a single case of mortality in this cohort. Although it was not statistically significant, CVE after CABG was more frequent in patients with bilateral carotid disease. CONCLUSIONS: Our results showed that staged CAS could be performed with minimal adverse outcomes in patients suffering from a simultaneous occlusive disease of carotids and coronary arteries before CABG. Bilateral CAS will further decrease cerebrovascular events and could be performed consequently or concomitantly.
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Estenosis Carotídea , Endarterectomía Carotidea , Accidente Cerebrovascular , Humanos , Arterias Carótidas , Estenosis Carotídea/cirugía , Puente de Arteria Coronaria/efectos adversos , Puente de Arteria Coronaria/métodos , Endarterectomía Carotidea/efectos adversos , Factores de Riesgo , Stents , Accidente Cerebrovascular/etiología , Resultado del TratamientoRESUMEN
OBJECTIVE: We describe a rare case of pseudohyponatremia in the setting of hypercholesterolemia caused by cholestasis due to metastatic liver disease and provide a review of the published cases in the literature. CASE REPORT: We report a case of pseudohyponatremia in a 60-year-old man with rectal cancer with extensive metastasis to the liver. While assessing the patient for hyponatremia, extremely elevated serum cholesterol with normal serum osmolality was detected leading to the diagnosis of pseudohyponatremia. This is one of very few reports of pseudohyponatremia in patients with elevated cholesterol in cholestatic liver disease. CONCLUSION: Hypercholesterolemia is an exceedingly rare cause for pseudohyponatremia. Although pseudohyponatremia per se does not carry a risk to the patient, the delay in diagnosis and treatment plans may pose additional risks. Pseudohyponatremia needs to be considered in patients with low sodium and co-existing cholestasis from metastatic liver disease.
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Colestasis Intrahepática , Colestasis , Hipercolesterolemia , Hiponatremia , Neoplasias , Masculino , Humanos , Persona de Mediana Edad , Hipercolesterolemia/complicaciones , Hiponatremia/diagnóstico , Hiponatremia/etiología , Colestasis Intrahepática/complicaciones , Colestasis/complicaciones , Neoplasias/complicacionesRESUMEN
Mitochondria are critical multifunctional organelles in cells that generate power, produce reactive oxygen species, and regulate cell survival. Mitochondria that are dysfunctional are eliminated via mitophagy as a way to protect cells under moderate stress and physiological conditions. However, mitophagy is a double-edged sword and can trigger cell death under severe stresses. By targeting mitochondria, photodynamic (PD) and photothermal (PT) therapies may play a role in treating cancer. These therapeutic modalities alter mitochondrial membrane potential, thereby affecting respiratory chain function and generation of reactive oxygen species promotes signaling pathways for cell death. In this regard, PDT, PTT, various mitochondrion-targeting agents and therapeutic methods could have exploited the vital role of mitochondria as the doorway to regulated cell death. Targeted mitochondrial therapies would provide an excellent opportunity for effective mitochondrial injury and accurate tumor erosion. Herein, we summarize the recent progress on the roles of PD and PT treatments in regulating cancerous cell death in relation to mitochondrial targeting and the signaling pathways involved.
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Neoplasias , Fotoquimioterapia , Humanos , Mitocondrias/metabolismo , Neoplasias/tratamiento farmacológico , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Terapia Fototérmica , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Monoclonal antibodies (mAbs) as biological macromolecules have been remarked the large and growing pipline of the pharmaceutical market and also the most promising tool in modern medicine for cancer therapy. These therapeutic entities, which consist of whole mAbs, armed mAbs (i.e., antibody-toxin conjugates, antibody-drug conjugates, and antibody-radionuclide conjugates), and antibody fragments, mostly target tumor cells. However, due to intrinsic heterogeneity of cancer diseases, tumor cells targeting mAb have been encountered with difficulties in their unpredictable efficacy as well as variability in remission and durable clinical benefits among cancer patients. To address these pitfalls, the area has undergone two major evolutions with the intent of minimizing anti-drug responses and addressing limitations experienced with tumor cell-targeted therapies. As a novel hallmark of cancer, the tumor microenvironment (TME) is becoming the great importance of attention to develop innovative strategies based on therapeutic mAbs. Here, we underscore innovative strategies targeting TME by mAbs which destroy tumor cells indirectly through targeting vasculature system (e.g., anti-angiogenesis), immune system modulation (i.e., stimulation, suppression, and depletion), the targeting and blocking of stroma-based growth signals (e.g., cancer-associated fibroblasts), and targeting cancer stem cells, as well as, their effector mechanisms, clinical uses, and relevant mechanisms of resistance.