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The role of direct oral anticoagulants (DOAC) in patients with atrial fibrillation (AF) and stage 4-5 chronic kidney disease (CKD) is controversial. Electronic medical records from 2012 to 2021 were retrieved for patients with AF and stage 4-5 CKD receiving oral anticoagulants. Patients were separated into those receiving DOACs (dabigatran, rivaroxaban, apixaban, or edoxaban) or vitamin K antagonists (VKA). Primary outcomes included ischemic stroke (IS), systemic thrombosis (SE), major bleeding, gastrointestinal bleeding, hemorrhagic stroke, acute myocardial infarction, cardiovascular death, and all-cause death. Renal outcomes included eGFR declines, creatinine doubling, progression to dialysis, and major adverse kidney events (MAKE). The primary analysis was until the end of follow up and the results at 1-year and 2-year of follow ups were also assessed. 2,382 patients (DOAC = 1,047, VKA = 1,335) between 2012 and 2021 with AF and stage 4-5 CKD were identified. The mean follow-up period was 2.3 ± 2.1 years in DOCAs and 2.6 ± 2.3 years in VKA respectively. At the end of follow up, the DOAC patients had significantly decreased SE (subdistribution hazard ratio [SHR] = 0.50, 95% confidence interval [CI] = 0.34-0.73), composite of IS/SE (SHR = 0.78, 95% CI = 0.62-0.98), major bleeding (HR = 0.77, 95% CI = 0.66-0.90), hemorrhagic stroke (HR = 0.52, 95% CI = 0.36-0.76), and composite of bleeding events (SHR = 0.80, 95% CI = 0.69-0.92) compared with VKA patients. The IS efficacy outcome revealed neutral between DOAC and VKA patients (HR = 1.05, 95% CI = 0.79-1.39). In addition, DOAC patients had significantly decreased rates of eGFR decline > 50% (SHR = 0.75, 95% CI = 0.64-0.87), creatinine doubling (SHR = 0.80, 95% CI = 0.67-0.95), and MAKE (SHR = 0.81, 95% CI = 0.71-0.93). In patients with AF and stage 4-5 CKD, use of DOAC was associated with decreased rates of a composite of ischemic stroke/systemic embolism, a composite of bleeding events, and renal events compared to VKA. Efficacy and safety benefits associated with apixaban at standard doses were consistent throughout follow-up.
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Fibrilación Atrial , Accidente Cerebrovascular Hemorrágico , Accidente Cerebrovascular Isquémico , Fallo Renal Crónico , Accidente Cerebrovascular , Humanos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Accidente Cerebrovascular Hemorrágico/inducido químicamente , Accidente Cerebrovascular Hemorrágico/complicaciones , Accidente Cerebrovascular Hemorrágico/tratamiento farmacológico , Estudios Retrospectivos , Creatinina , Anticoagulantes/efectos adversos , Rivaroxabán/efectos adversos , Hemorragia/inducido químicamente , Hemorragia/tratamiento farmacológico , Fallo Renal Crónico/complicaciones , Riñón , Accidente Cerebrovascular Isquémico/complicaciones , Accidente Cerebrovascular/tratamiento farmacológico , Administración OralRESUMEN
BACKGROUND: The standard curative treatments for extremity soft tissue sarcoma (ESTS) include surgical resection with negative margins and perioperative radiotherapy. However, the optimal resection margin remains controversial. This study aimed to evaluate the outcomes in ESTS between microscopically positive margin (R1) and microscopically negative margin (R0) according to the Union for International Cancer Control (UICC) (R + 1 mm) classification. METHODS: Medical records of patients with localized ESTS who underwent primary limb-sparing surgery and postoperative radiotherapy between 2004 and 2015 were retrospectively reviewed. Patients were followed for at least 5 years or till local or distant recurrence was diagnosed during follow-up. Outcomes were local and distal recurrences and survival. RESULTS: A total of 52 patients were included in this study, in which 17 underwent R0 resection and 35 underwent R1 resection. No significant differences were observed in rates of local recurrence (11.4% vs. 35.3%, p = 0.062) or distant recurrence (40.0% vs. 41.18%, p = 0.935) between R0 and R1 groups. Multivariate analysis showed that distant recurrences was associated with a Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grade (Grade III vs. I, adjusted hazard ratio (aHR): 12.53, 95% confidence interval (CI): 2.67-58.88, p = 0.001) and tumor location (lower vs. upper extremity, aHR: 0.23, 95% CI: 0.07-0.7, p = 0.01). Kaplan-Meier plots showed no significant differences in local (p = 0.444) or distant recurrent-free survival (p = 0.161) between R0 and R1 groups. CONCLUSIONS: R1 margins, when complemented by radiotherapy, did not significantly alter outcomes of ESTS as R0 margins. Further studies with more histopathological types and larger cohorts are necessary to highlight the path forward.
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Extremidades , Márgenes de Escisión , Recurrencia Local de Neoplasia , Sarcoma , Humanos , Masculino , Femenino , Persona de Mediana Edad , Sarcoma/cirugía , Sarcoma/patología , Sarcoma/radioterapia , Sarcoma/mortalidad , Estudios Retrospectivos , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/cirugía , Extremidades/patología , Extremidades/cirugía , Adulto , Estudios de Seguimiento , Tasa de Supervivencia , Anciano , Pronóstico , Radioterapia Adyuvante/métodos , Radioterapia Adyuvante/estadística & datos numéricos , Tratamientos Conservadores del Órgano/métodos , Tratamientos Conservadores del Órgano/estadística & datos numéricos , Adulto Joven , Neoplasias de los Tejidos Blandos/cirugía , Neoplasias de los Tejidos Blandos/patología , Neoplasias de los Tejidos Blandos/radioterapia , Neoplasias de los Tejidos Blandos/mortalidad , AdolescenteRESUMEN
BACKGROUND: In total knee arthroplasty (TKA), isolated aseptic loosening (IAL) requires the replacement of prosthetic components, with ongoing debate regarding the effectiveness of partial component revision (PCR) compared to total component revision (TCR). This study aims to compare implant survival and surgical outcomes between PCR and TCR in the context of IAL. METHODS: This retrospective study analyzed data from 285 patients who underwent revision TKA for IAL between January 2000 and December 2013. After applying exclusion criteria, 112 patients were included in the analysis-60 undergoing TCR and 52 undergoing PCR. RESULTS: PCR was associated with shorter operative times and hospital stays compared to TCR, alongside significant differences in the choice of revision prostheses. Although the prosthesis failure rates were comparable between the groups (13.6% for TCR and 18.33% for PCR), significant risk factors for failure were identified, including a canal filling ratio (CFR) below 0.8 and a discrepancy over 0.2 between CFR views. However, no significant differences in overall survivorship were observed between the groups. CONCLUSIONS: Both PCR and TCR provide similar survival rates and clinical outcomes for managing IAL in TKA. PCR provides advantages in terms of surgical efficiency and patient recovery, while reducing the need for more constrained prosthetic solutions. The study identifies CFR as a critical predictor of prosthesis failure, highlighting the importance of detailed preoperative planning and implant selection. These findings contribute valuable insights for improving revision strategies in IAL, enhancing surgical outcomes in TKA. LEVEL OF EVIDENCE: III.
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Artroplastia de Reemplazo de Rodilla , Prótesis de la Rodilla , Falla de Prótesis , Reoperación , Humanos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Artroplastia de Reemplazo de Rodilla/instrumentación , Artroplastia de Reemplazo de Rodilla/métodos , Masculino , Femenino , Estudios Retrospectivos , Anciano , Reoperación/estadística & datos numéricos , Persona de Mediana Edad , Prótesis de la Rodilla/efectos adversos , Resultado del Tratamiento , Anciano de 80 o más Años , Factores de RiesgoRESUMEN
BACKGROUND: This study aimed to report the long-term survival of fixed-bearing medial unicompartmental knee arthroplasty (UKA) with a mean of 14-year follow-up, and to determine possible risk factors of failure. METHODS: We retrospectively evaluated 337 fixed-bearing medial UKAs implanted between 2003 and 2014. Demographic and radiographic parameters were measured, including pre-operative and post-operative anatomical femorotibial angle (aFTA), posterior tibial slope (PTS), and anatomical medial proximal tibial angle (aMPTA). Multivariate logistic regression analysis was applied to figure out risk factors. RESULTS: The mean follow-up time was 14.0 years. There were 32 failures categorized into implant loosening (n = 11), osteoarthritis progression (n = 7), insert wear (n = 7), infection (n = 4), and periprosthetic fracture (n = 3). Cumulative survival was 91.6% at 10 years and 90.0% at 15 years. No statistically significant parameters were found between the overall survival and failure groups. Age and hypertension were significant factors of implant loosening with odds ratio (OR) 0.909 (p = 0.02) and 0.179 (p = 0.04) respectively. In the insert wear group, post-operative aFTA and correction of PTS showed significance with OR 0.363 (p = 0.02) and 0.415 (p = 0.03) respectively. Post-operative aMPTA was a significant factor of periprosthetic fracture with OR 0.680 (p < 0.05). CONCLUSIONS: The fixed-bearing medial UKA provides successful long-term survivorship. Tibial component loosening is the major cause of failure. Older age and hypertension were factors with decreased risk of implant loosening.
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Artroplastia de Reemplazo de Rodilla , Hipertensión , Fracturas Periprotésicas , Humanos , Supervivencia , Artroplastia de Reemplazo de Rodilla/efectos adversos , Estudios de Seguimiento , Estudios RetrospectivosRESUMEN
BACKGROUND: The successful treatment and improvement of acute kidney injury (AKI) depend on early-stage diagnosis. However, no study has differentiated between the three stages of AKI and non-AKI patients following heart surgery. This study will fill this gap in the literature and help to improve kidney disease management in the future. METHODS: In this study, we applied Raman spectroscopy (RS) to uncover unique urine biomarkers distinguishing heart surgery patients with and without AKI. Given the amplified risk of renal complications post-cardiac surgery, this approach is of paramount importance. Further, we employed the partial least squares-support vector machine (PLS-SVM) model to distinguish between all three stages of AKI and non-AKI patients. RESULTS: We noted significant metabolic disparities among the groups. Each AKI stage presented a distinct metabolic profile: stage 1 had elevated uric acid and reduced creatinine levels; stage 2 demonstrated increased tryptophan and nitrogenous compounds with diminished uric acid; stage 3 displayed the highest neopterin and the lowest creatinine levels. We utilized the PLS-SVM model for discriminant analysis, achieving over 90% identification rate in distinguishing AKI patients, encompassing all stages, from non-AKI subjects. CONCLUSIONS: This study characterizes the incidence and risk factors for AKI after cardiac surgery. The unique spectral information garnered from this study can also pave the way for developing an in vivo RS method to detect and monitor AKI effectively.
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Lesión Renal Aguda , Biomarcadores , Procedimientos Quirúrgicos Cardíacos , Espectrometría Raman , Urinálisis , Humanos , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/orina , Lesión Renal Aguda/etiología , Espectrometría Raman/métodos , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Biomarcadores/orina , Urinálisis/métodos , Creatinina/orina , Máquina de Vectores de Soporte , Ácido Úrico/orina , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/orina , Complicaciones Posoperatorias/etiología , Factores de Riesgo , Análisis de los Mínimos CuadradosRESUMEN
BACKGROUND: The clinical challenge of unexpected positive intraoperative cultures (UPICs) persists in 2-stage resection arthroplasty for managing periprosthetic joint infections (PJIs) following total knee arthroplasty.(TKA). This study aimed to investigate the incidence of UPICs during the definitive reimplantation phase of 2-stage resection arthroplasty of the knee and to assess both the infection-free and revision-free survivorship of the implanted prosthesis. METHODS: This retrospective study included 450 2-stage resection arthroplasties of primary knee prostheses performed between January 2012 and April 2017. Patients were excluded if they: (1) underwent three or more staged resections, (2) had ambiguous clinical documentation or deviated from the 2-stage protocol, or (3) underwent revision arthroplasty prior to the PJI. Additionally, patients presumed aseptic before the second-stage reimplantation were excluded if they lacked joint aspiration or met the 2011 Musculoskeletal Infection Society criteria for PJI before implantation. RESULTS: After exclusions, 300 patients were analyzed. Among them, 14% had UPIC during the second-stage reimplantation. The follow-up time was 2,316 (range, 1,888 to 3,737) days and 2,531 (range, 1,947 to 3,349) days for UPIC and negative intraoperative culture (NIC) groups, respectively. Rerevision due to subsequent PJI occurred in 26.2% of UPIC patients and 15.1% of NIC patients. The 2-year infection-free survival rates for the NIC, one UPIC, and ≥ two UPIC cohorts were 99.5, 98.2, and 94.3%, respectively, while the 5-year survival rates were 92.1, 91.1, and 54.3%, respectively. The unfavorable survivorship was significantly different in multiple UPIC cases (P < 0.001). Multiple UPICs with pathogens consistent with the first-stage findings were strongly associated with the risk of reinfection (P < 0.001). CONCLUSIONS: An UPIC was identified in 14% of second-stage reimplantations. Patients who had multiple UPICs demonstrated truncated survivorship and suboptimal outcomes relative to the NIC and single UPIC cohorts, especially with pathogen consistency to the first-stage surgery. LEVEL OF EVIDENCE: III.
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Acute kidney injury is a common and complex complication that has high morality and the risk for chronic kidney disease among survivors. The accuracy of current AKI biomarkers can be affected by water retention and diuretics. Therefore, we aimed to identify a urinary non-recovery marker of acute kidney injury in patients with acute decompensated heart failure. We used the isobaric tag for relative and absolute quantification technology to find a relevant marker protein that could divide patients into control, acute kidney injury with recovery, and acute kidney injury without recovery groups. An enzyme-linked immunosorbent assay of the endothelial cell protein C receptor (EPCR) was used to verify the results. We found that the EPCR was a usable marker for non-recovery renal failure in our setting with the area under the receiver operating characteristics 0.776 ± 0.065; 95%CI: 0.648-0.905, (p < 0.001). Further validation is needed to explore this possibility in different situations.
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Lesión Renal Aguda , Factores de Coagulación Sanguínea , Insuficiencia Cardíaca , Receptores de Superficie Celular , Humanos , Receptor de Proteína C Endotelial , Proteómica , Pronóstico , Riñón , Lesión Renal Aguda/etiología , Insuficiencia Cardíaca/complicaciones , BiomarcadoresRESUMEN
Cholangiocarcinoma (CCA) is an aggressive malignant tumor of bile duct epithelia. Recent evidence suggests the impact of cancer stem cells (CSC) on the therapeutic resistance of CCA; however, the knowledge of CSC in CCA is limited due to the lack of a CSC model. In this study, we successfully established a stable sphere-forming CCA stem-like cell, KKU-055-CSC, from the original CCA cell line, KKU-055. The KKU-055-CSC exhibits CSC characteristics, including: (1) the ability to grow stably and withstand continuous passage for a long period of culture in the stem cell medium, (2) high expression of stem cell markers, (3) low responsiveness to standard chemotherapy drugs, (4) multilineage differentiation, and (5) faster and constant expansive tumor formation in xenograft mouse models. To identify the CCA-CSC-associated pathway, we have undertaken a global proteomics and functional cluster/network analysis. Proteomics identified the 5925 proteins in total, and the significantly upregulated proteins in CSC compared with FCS-induced differentiated CSC and its parental cells were extracted. Network analysis revealed that high mobility group A1 (HMGA1) and Aurora A signaling through the signal transducer and activator of transcription 3 pathways were enriched in KKU-055-CSC. Knockdown of HMGA1 in KKU-055-CSC suppressed the expression of stem cell markers, induced the differentiation followed by cell proliferation, and enhanced sensitivity to chemotherapy drugs including Aurora A inhibitors. In silico analysis indicated that the expression of HMGA1 was correlated with Aurora A expressions and poor survival of CCA patients. In conclusion, we have established a unique CCA stem-like cell model and identified the HMGA1-Aurora A signaling as an important pathway for CSC-CCA.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Humanos , Ratones , Animales , Proteína HMGA1a , Colangiocarcinoma/metabolismo , Células Madre Neoplásicas/metabolismo , Conductos Biliares Intrahepáticos/metabolismo , Neoplasias de los Conductos Biliares/metabolismo , Línea Celular Tumoral , Proliferación CelularRESUMEN
Background Diabetes mellitus may be associated with an increased likelihood of CT contrast material-induced acute kidney injury (CI-AKI), but this has not been studied in a large sample with and without kidney dysfunction. Purpose To investigate whether diabetic status and estimated glomerular filtration rate (eGFR) are associated with the likelihood of acute kidney injury (AKI) following CT contrast material administration. Materials and Methods This retrospective multicenter study included patients from two academic medical centers and three regional hospitals who underwent contrast-enhanced CT (CECT) or noncontrast CT between January 2012 and December 2019. Patients were stratified according to eGFR and diabetic status, and subgroup-specific propensity score analyses were performed. The association between contrast material exposure and CI-AKI was estimated with use of overlap propensity score-weighted generalized regression models. Results Among the 75 328 patients (mean age, 66 years ± 17 [SD]; 44 389 men; 41 277 CECT scans; 34 051 noncontrast CT scans), CI-AKI was more likely in patients with an eGFR of 30-44 mL/min/1.73 m2 (odds ratio [OR], 1.34; P < .001) or less than 30 mL/min/1.73 m2 (OR, 1.78; P < .001). Subgroup analyses revealed higher odds of CI-AKI among patients with an eGFR less than 30 mL/min/1.73 m2, with or without diabetes (OR, 2.12 and 1.62; P = .001 and .003, respectively), when they underwent CECT compared with noncontrast CT. Among patients with an eGFR of 30-44 mL/min/1.73 m2, the odds of CI-AKI were higher only in those with diabetes (OR, 1.83; P = .003). Patients with an eGFR less than 30 mL/min/1.73 m2 and diabetes had higher odds of 30-day dialysis (OR, 1.92; P = .005). Conclusion Compared with noncontrast CT, CECT was associated with higher odds of AKI in patients with an eGFR of less than 30 mL/min/1.73 m2 and in patients with diabetes with an eGFR of 30-44 mL/min/1.73 m2; higher odds of 30-day dialysis were observed only in patients with diabetes with an eGFR less than 30 mL/min/1.73 m2. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Davenport in this issue.
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Lesión Renal Aguda , Diabetes Mellitus , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Masculino , Humanos , Anciano , Medios de Contraste/efectos adversos , Tasa de Filtración Glomerular , Estudios Retrospectivos , Diabetes Mellitus/epidemiología , Tomografía Computarizada por Rayos X/métodos , Lesión Renal Aguda/diagnóstico por imagen , Lesión Renal Aguda/inducido químicamente , Medición de Riesgo , Riñón/diagnóstico por imagen , Factores de RiesgoRESUMEN
RATIONALE & OBJECTIVE: Dialysis-treated acute kidney injury (AKI) is increasingly common in intensive care units (ICUs) and is associated with poor outcomes. Few studies have explored the temporal trends in severity of acute illness at dialysis initiation, indications for dialysis, and their association with patient outcomes. STUDY DESIGN: Multicenter retrospective cohort study. SETTING & PARTICIPANTS: 9,535 adult patients admitted to the ICU who received their first dialysis treatment from Chang Gung Memorial Hospital system in Taiwan from 2009 through 2018. EXPOSURE: Calendar year. OUTCOMES: ICU mortality and dialysis treatment at discharge among hospital survivors. ANALYTICAL APPROACH: The temporal trends during the study period were investigated using test statistics suited for continuous or categorical data. The association between the study year and the risk of mortality was analyzed using multivariable Cox regression with adjustment for relevant clinical variables, including the severity of acute illness, defined by Sequential Organ Failure Assessment (SOFA) score. RESULTS: The mean SOFA score at dialysis initiation decreased slightly from 14.0 in 2009 to 13.6 in 2018. There was no significant trend in the number of indications for dialysis initiation that were fulfilled over time. Observed ICU mortality decreased over time, and the curve appeared to be reverse J-shaped, with a substantial decrease from 56.1% in 2009 to 46.3% in 2015 and a slight increase afterward. The risk of mortality was significantly reduced from 2013 to 2018 compared with 2009 in adjusted models. The decreasing trend in ICU mortality over time remained significant. There was an increase in dialysis treatment at discharge among survivors, mainly in patients with estimated glomerular filtration rate<60mL/min/1.73m2, from 36.8% in 2009 to 43.9% in 2018. LIMITATIONS: Residual confounding from unmeasured factors over time such as severity of comorbidities, detailed medication interventions, and delivered dialysis dose. CONCLUSIONS: We observed reductions in mortality among ICU patients with dialysis-treated acute kidney injury between 2009 and 2018, even after adjusting for dialysis indication and severity of illness at dialysis initiation. However, dialysis treatment at discharge among survivors has increased over time, mainly in patients with preexisting kidney disease. PLAIN-LANGUAGE SUMMARY: The current medical management of severe acute kidney injury (AKI) is primarily limited to supportive care and kidney replacement therapy if indicated, leading to perceptions that outcomes among intensive care unit (ICU) patients with dialysis-treated AKI have not improved. In this multicenter retrospective study of ICU patients with dialysis-treated AKI between 2009 and 2018 in Taiwan, patient mortality decreased over time despite increasing comorbidities. Moreover, the decreasing linear trends remained significant even when considering severity of acute illness at dialysis initiation, which was based on physiologic and laboratory measurements seldom evaluated in previous studies. Further research should explore the basis for these improvements.
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Lesión Renal Aguda , Diálisis Renal , Adulto , Humanos , Estudios Retrospectivos , Enfermedad Aguda , Unidades de Cuidados Intensivos , Terapia de Reemplazo Renal , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/terapia , Enfermedad CríticaRESUMEN
BACKGROUND: To determine whether glucagon-like peptide 1 receptor agonists (GLP-1RAs) have cardiovascular and renal protective effects in patients with advanced diabetic kidney disease (DKD) with an estimated glomerular filtration rate (eGFR) < 30 mL/min per 1.73 m2. METHODS: In this cohort study, patients with type 2 diabetes mellitus and eGFR < 30 mL/min per 1.73 m2 with a first prescription for GLP-1RAs or dipeptidyl peptidase 4 inhibitors (DPP-4is) from 2012 to 2021 (n = 125,392) were enrolled. A Cox proportional hazard model was used to assess the cardiorenal protective effects between the GLP-1RA and DDP-4i groups. RESULTS: A total of 8922 participants [mean (SD) age 68.4 (11.5) years; 4516 (50.6%) males; GLP-1RAs, n = 759; DPP-4is, n = 8163] were eligible for this study. During a mean follow-up of 2.1 years, 78 (13%) and 204 (13.8%) patients developed composite cardiovascular events in the GLP-1RA and DPP-4i groups, respectively [hazard ratio (HR) 0.88, 95% confidence interval CI 0.68-1.13]. Composite kidney events were reported in 134 (38.2%) and 393 (44.2%) patients in the GLP-1RA and DPP-4i groups, respectively (subdistribution HR 0.72, 95% CI 0.56-0.93). CONCLUSIONS: GLP-1RAs had a neutral effect on the composite cardiovascular outcomes but reduced composite kidney events in the patients with advanced DKD compared with DPP-4is.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Receptor del Péptido 1 Similar al Glucagón , Anciano , Femenino , Humanos , Masculino , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Estudios de Cohortes , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/epidemiología , Inhibidores de la Dipeptidil-Peptidasa IV , Péptido 1 Similar al Glucagón , Receptor del Péptido 1 Similar al Glucagón/agonistas , Hipoglucemiantes , RiñónRESUMEN
BACKGROUND: Knee osteoarthritis (OA) is a leading cause of disability among older adults. Medical and surgical treatments are costly and associated with side effects. A natural nutraceutical, collagen hydrolysate, has received considerable attention due to its relieving effects on OA-associated symptoms. This study investigated the effects of hydrolyzed collagen type II (HC-II) and essence of chicken (BRAND'S Essence of Chicken) with added HC-II (EC-HC-II) on joint, muscle, and bone functions among older adults with OA. METHODS: Patients (n = 160) with grade 1-3 knee OA according to the Kellgren-Lawrence classification system, joint pain for ≥ 3 months, and a Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score of > 6 were randomly assigned with equal probability to consume EC-HC-II, HC-II, glucosamine HCl, or a placebo for 24 weeks in combination with resistance training. Outcome measurements were WOMAC score, visual analogue scale (VAS) pain score, grip strength, fat-free mass (FFM), and bone mass. RESULTS: All groups exhibited similar levels of improvement in WOMAC index scores after 24 weeks. HC-II significantly reduced VAS pain score by 0.9 ± 1.89 (p = 0.034) after 14 days. A repeated-measures analysis of variance showed that HC-II reduced pain levels more than the placebo did (mean ± standard error: - 1.3 ± 0.45, p = 0.021) after 14 days; the EC-HC-II group also had significantly higher FFM than the glucosamine HCl (p = 0.02) and placebo (p = 0.017) groups and significantly higher grip strength than the glucosamine HCl group (p = 0.002) at 24 weeks. CONCLUSION: HC-II reduces pain, and EC-HC-II may improve FFM and muscle strength. This suggests that EC-HC-II may be a novel holistic solution for mobility by improving joint, muscle, and bone health among older adults. Large-scale studies should be conducted to validate these findings. TRIAL REGISTRATION: This trial was retrospectively registered at ClinicalTrials.gov (NCT04483024).
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Pollos , Osteoartritis de la Rodilla , Animales , Humanos , Colágeno Tipo II/uso terapéutico , Proyectos Piloto , Osteoartritis de la Rodilla/complicaciones , Osteoartritis de la Rodilla/tratamiento farmacológico , Dolor/complicaciones , Dolor/tratamiento farmacológico , Glucosamina/uso terapéutico , Músculos , Método Doble Ciego , Resultado del TratamientoRESUMEN
We developed a simple and rapid method to enrich protein N-terminal peptides, in which the protease TrypN is first employed to generate protein N-terminal peptides without Lys or Arg and internal peptides with two positive charges at their N termini, and then, the N-terminal peptides with or without N-acetylation are separated from the internal peptides by strong cation exchange chromatography according to a retention model based on the charge/orientation of peptides. This approach was applied to 20 µg of human HEK293T cell lysate proteins to profile the N-terminal proteome. On average, 1550 acetylated and 200 unmodified protein N-terminal peptides were successfully identified in a single LC/MS/MS run with less than 3% contamination with internal peptides, even when we accepted only canonical protein N termini registered in the Swiss-Prot database. Because this method involves only two steps, protein digestion and chromatographic separation, without the need for tedious chemical reactions, it should be useful for comprehensive profiling of protein N termini, including proteoforms with neo-N termini.
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Péptidos/química , Tripsina/química , Acetilación , Cromatografía Líquida de Alta Presión , Cromatografía por Intercambio Iónico , Proteínas de Escherichia coli/química , Células HEK293 , Humanos , Proteómica/métodos , Espectrometría de Masas en TándemRESUMEN
BACKGROUND: The impact of sex-related differences in patients receiving extracorporeal membrane oxygenation support (ECMO) support is still inconclusive. This population-based study aimed to investigate sex differences in short- or long-term outcomes in order to improve clinical practice. METHODS: Patients who received ECMO between 2001 to 2017 were identified from the Taiwan National Health Insurance Research Database. Propensity score matching with a 1:1 ratio was conducted in female-to-male groups, to reduce confounding of baseline covariates. Outcomes included in-hospital mortality, all-cause mortality, all-cause readmission, and ECMO-related complications. Logistic regression analysis, Cox proportional hazard model, and join point regression were used to compare sex differences in both short- or long-term outcomes. RESULTS: In total, 7,010 matched patients from 11,734 ECMO receivers were included for analysis. The use of ECMO increased dramatically in past years, although the proportion of females was still lower than males. There was a decreasing trend of females undergoing ECMO over time. Female patients have lower risks of in-hospital mortality (64.08% in females vs 66.48% in males; P = 0.0352) and ECMO-related complications compared with males. Furthermore, females also had favorable long-term late outcomes such as all-cause mortality (73.35% in females vs 76.98% in males; P = 0.009) and readmission rate (6.99% in females vs 9.19% in males; P = 0.001). CONCLUSIONS: Female patients had more favorable in-hospital and long-term survival outcomes. Despite improvement in modern ECMO technique and equipment, ECMO remains underutilized in eligible female patients. Thus, females should undergo ECMO treatment if available and indicated. TRIAL REGISTRATION: The institutional review board of Chang Gung Memorial Hospital approved all data usage and the study protocol (registration number: 202100151B0C502; date of registration: 23/08/2021).
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Oxigenación por Membrana Extracorpórea , Insuficiencia Respiratoria , Humanos , Masculino , Femenino , Oxigenación por Membrana Extracorpórea/métodos , Taiwán/epidemiología , Caracteres Sexuales , Mortalidad Hospitalaria , Insuficiencia Respiratoria/terapia , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
PURPOSE: The advantages of unicompartmental knee arthroplasty (UKA) have led to the procedure being increasingly performed worldwide. However, revision surgery is required after UKA failure. According to the literature review, the choice of implant in revision surgery remains a debatable concern. This study analyzed the clinical results of different types of prostheses used in treating failed UKA. MATERIALS AND METHODS: This is a retrospective review of 33 failed medial UKAs between 2006 and 2017. Demographic data, failure reason, types of revision prostheses, and the severity of bone defects were analyzed. The patients were classified into three groups: primary prosthesis, primary prosthesis with a tibial stem, and revision prosthesis. The implant survival rate and medical cost of the procedures were compared. RESULTS: A total of 17 primary prostheses, 7 primary prostheses with tibial stems, and 9 revision prostheses were used. After a mean follow-up of 30.8 months, the survival outcomes of the three groups were 88.2%, 100%, and 88.9%, respectively (P = 0.640). The common bone defect in tibia site is Anderson Orthopedic Research Institute [AORI] grade 1 and 2a (16 versus 17). In patients with tibial bone defects AORI grade 2a, the failure rates of primary prostheses and primary prostheses with tibial stems were 25% and 0%, respectively. CONCLUSIONS: The most common cause for UKA failure was aseptic loosening. The adoption of a standardized surgical technique makes it easier to perform revision surgeries. Primary prostheses with tibial stems provided higher stability, leading to a lower failure rate due to less risk of aseptic loosening in patients with tibial AORI grade 2a. In our experience, we advise surgeons may try using primary prostheses in patients with tibial AORI grade 1 and primary prostheses with tibial stems in patients with tibial AORI grade 2a.
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Artroplastia de Reemplazo de Rodilla , Prótesis de la Rodilla , Humanos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Artroplastia de Reemplazo de Rodilla/métodos , Reoperación/efectos adversos , Resultado del Tratamiento , Falla de Prótesis , Prótesis de la Rodilla/efectos adversos , Estudios Retrospectivos , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/cirugíaRESUMEN
BACKGROUND: Two-stage exchange arthroplasty is considered the gold standard treatment for chronic periprosthetic joint infection (PJI). However, there is a scarcity of research investigating the major risk factors for infection recurrence and the prognosis after infection recurrence. METHODS: This study included 203 patients who underwent 2-stage exchange arthroplasty between June 22, 2010 and January 24, 2017. The need of reoperation for infection-related or PJI-related mortality was considered treatment failure. Participant age, gender, body mass index, comorbidities, culture results, length of hospital stay, cause of treatment failure, operative procedure, and fate were analyzed. RESULTS: Fifty-three patients experienced treatment failure (26.1%). Mean follow-up was 63 months (range, 26-103). Based on the multivariate analyses, risk factors for treatment failure included men and positive intraoperative culture during reimplantation. Recurrent infection was most commonly caused by Staphylococcus aureus (32.1%, 17/53), and new microorganisms caused recurrent infection in 34 of 53 (64.2%) patients. In 44 patients who had treatment failure, debridement, antibiotic therapy, irrigation, and retention of prosthesis (DAIR) performed within 6 months of reimplantation and at <3 weeks from symptom onset resulted in a significantly higher success rate than the use of other DAIR protocols (P = .031). CONCLUSION: Men and positive intraoperative culture are major risk factors for 2-stage exchange arthroplasty failure in patients who have knee PJI. Recurrent infection in these patients is usually caused by new microorganisms. DAIR within 6 months of reimplantation and at <3 weeks from symptom onset results in good outcomes in these patients.
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Artroplastia de Reemplazo de Rodilla , Infecciones Relacionadas con Prótesis , Masculino , Humanos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Resultado del Tratamiento , Reinfección/complicaciones , Reinfección/tratamiento farmacológico , Infecciones Relacionadas con Prótesis/etiología , Infecciones Relacionadas con Prótesis/cirugía , Insuficiencia del Tratamiento , Antibacterianos/uso terapéutico , Factores de Riesgo , Reoperación/efectos adversos , Estudios Retrospectivos , Desbridamiento/efectos adversosRESUMEN
Background and Objectives: The efficacy of tranexamic acid (TXA) in reducing perioperative blood loss during total knee arthroplasty (TKA) is well established. However, the potential synergistic blood-conservation effect of topical fibrin sealant (Tisseel@) remains unclear. This study aims to assess the effectiveness of the combination of Tisseel and TXA during TKA. Materials and Methods: A single-blinded, prospective, randomized controlled trial was conducted with 100 patients (100 knees) undergoing primary TKA. Participants were randomly assigned to either the TXA group (n = 50), receiving intravenous (IV) TXA, or the Tisseel@ + TXA group (n = 50), receiving intra-articular Tisseel@ combined with IV TXA. The primary outcomes included blood transfusion rate, decrease in Hb level, calculated blood loss, and estimated total postoperative blood loss. Secondary outcomes involved assessing clinical differences between the groups. Results: The transfusion rate was zero in both groups. The average estimated blood loss in the Tisseel@ + TXA group was 0.463 ± 0.2422 L, which was similar to that of the TXA group at 0.455 ± 0.2522 L. The total calculated blood loss in the Tisseel@ + TXA group was 0.259 ± 0.1 L, compared with the TXA group's 0.268 ± 0.108 L. The mean hemoglobin reduction in the first 24 h postoperatively was 1.57 ± 0.83 g/dL for the Tisseel@ + TXA group and 1.46 ± 0.82 g/dL for the TXA-only group. The reduction in blood loss in the topical Tisseel@ + TXA group was not significantly different from that achieved in the TXA-only group. The clinical results of TKA up to the 6-week follow-up were comparable between the groups. Conclusions: The combination of the topical fibrin sealant Tisseel@ and perioperative IV TXA administration, following the described protocol, demonstrated no significant synergistic blood-conservation effect in patients undergoing TKR.
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Antifibrinolíticos , Artroplastia de Reemplazo de Rodilla , Ácido Tranexámico , Humanos , Ácido Tranexámico/farmacología , Ácido Tranexámico/uso terapéutico , Adhesivo de Tejido de Fibrina/farmacología , Adhesivo de Tejido de Fibrina/uso terapéutico , Antifibrinolíticos/farmacología , Antifibrinolíticos/uso terapéutico , Artroplastia de Reemplazo de Rodilla/efectos adversos , Estudios Prospectivos , Pérdida de Sangre Quirúrgica/prevención & controlRESUMEN
Recent advances in single-cell proteomics highlight the promise of sensitive analyses in limited cell populations. However, technical challenges remain for sample recovery, throughput, and versatility. Here, we first report a water droplet-in-oil digestion (WinO) method based on carboxyl-coated beads and phase transfer surfactants for proteomic analysis using limited sample amounts. This method was developed to minimize the contact area between the sample solution and the container to reduce the loss of proteins and peptides by adsorption. This method increased protein and peptide recovery 10-fold. The proteome profiles obtained from 100 cells using the WinO method highly correlated with those from 10,000 cells using the in-solution digestion method. We successfully applied the WinO method to single-cell proteomics and quantified 462 proteins. Using the WinO method, samples can be easily prepared in a multi-well plate, making it a widely applicable and suitable method for single-cell proteomics.
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Proteoma , Proteómica , Digestión , Péptidos/análisis , Proteoma/análisis , Proteómica/métodos , AguaRESUMEN
BACKGROUND: Restless legs syndrome (RLS) is common among patients with end-stage kidney disease (ESKD) and is associated with poor outcomes. Several recently published studies had focused on pharmacological and non-pharmacological treatments of RLS, but an updated meta-analysis has not been conducted. METHODS: The study population was adult ESKD patients on dialysis with RLS. Randomized controlled trials (RCTs) were selected. The primary outcome was reduction in RLS severity. The secondary outcomes were improvement in sleep quality and treatment-related adverse events. Frequentist standard network meta-analysis (NMA) and additive component NMA were performed. The evidence certainty was assessed using the Confidence in NMA (CINeMA) framework. RESULTS: A total of 24 RCTs with 1252 participants were enrolled and 14 interventions were compared. Cool dialysate produced the largest RLS severity score reduction {mean difference [MD] 16.82 [95% confidence interval (CI) 10.635-23.02]} and a high level of confidence. Other potential non-pharmacological interventions include intradialytic stretching exercise [MD 12.00 (95% CI 7.04-16.97)] and aromatherapy massage [MD 10.91 (95% CI 6.96-14.85)], but all with limited confidence of evidence. Among the pharmacological interventions, gabapentin was the most effective [MD 8.95 (95% CI 1.95-15.85)], which also improved sleep quality [standardized MD 2.00 (95% CI 0.47-3.53)]. No statically significant adverse events were detected. CONCLUSIONS: The NMA supports that cool dialysate is appropriate to treat patients with ESKD and RLS. Gabapentin is the most effective pharmacological intervention and also might improve sleep quality. Further parallel RCTs with sufficient sample sizes are required to evaluate these potential interventions and long-term effects.
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Fallo Renal Crónico , Síndrome de las Piernas Inquietas , Adulto , Soluciones para Diálisis , Gabapentina/uso terapéutico , Humanos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Metaanálisis en Red , Diálisis Renal/efectos adversos , Síndrome de las Piernas Inquietas/tratamiento farmacológico , Síndrome de las Piernas Inquietas/terapiaRESUMEN
BACKGROUND: Patients with kidney failure who start dialysis have a chance of kidney function recovery. Whether the initial dialysis modality affects the possibility of recovery is not fully understood. METHODS: We included patients diagnosed with kidney failure requiring dialysis during 2001-2013 from the Taiwan National Health Insurance Research Database. We excluded diabetic and elderly patients. Kidney function recovery was defined as not receiving dialysis therapy for longer than 3 months. The primary outcome was kidney function recovery, and the secondary outcome was all-cause mortality during a 3-year follow up. RESULTS: A total of 12,619 patients was eligible for analysis, with 981 received PD and 11,638 received HD. Total 620 patients had kidney function recovery during a 3-year follow up, which represented 4.9% of the entire cohort. After propensity score matching, the PD groups were more likely to experience kidney function recovery (subdistribution hazard ratio [SHR]: 1.64, 95% confidence interval [CI]: 1.19-2.25). The risk of all-cause mortality between groups did not significantly differ (hazard ratio [HR]: 1.23, 95% CI: 0.89-1.70). CONCLUSION: The study found that in nonelderly, nondiabetic patients who received inadequate predialysis nephrology care before kidney failure, PD is associated with a higher chance of kidney function recovery.