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BACKGROUND: Long-term clinical outcomes of early intravascular ultrasound (IVUS) findings in a prospective cohort of heart transplantation (HTx) patients have not been evaluated. METHODS: This study included patients from 20 centers across Europe and North and South America among the original cohort of the RAD B253 study. Among these patients, 91 had paired IVUS images at baseline and 1-year post-transplant: everolimus 1.5 mg group (n = 25), everolimus 1.5 mg group (n = 33), and azathioprine 3.0 group (n = 33). The primary outcome was a composite of cardiovascular death, retransplantation, myocardial infarction (MI), coronary revascularization, and cardiac allograft vasculopathy (CAV) within a 10-year follow-up period. The secondary outcome was all-cause death, cardiovascular death, retransplantation, MI, coronary revascularization, and CAV. Donor disease was defined as baseline maximal intimal thickness (MIT) >0.66 mm, and rapid progression was defined as a change in MIT > 0.59 mm at 1 year. RESULTS: Donor disease (46 patients) was associated with a higher incidence of the primary outcome (hazard ratio (HR) 4.444, 95% confidence interval [CI] 1.946-10.146, p < 0.001). Rapid progression (44 patients) was associated with a significantly higher incidence of the primary outcome (HR 2.942, 95% CI 1.383-6.260, p = 0.005). Higher-risk features on IVUS (positive both donor disease and rapid progression) were independently associated with poor clinical outcomes (HR 4.800, 95% CI 1.816-12.684, p = 0.002). CONCLUSIONS: An increase in baseline MIT and a change in first-year MIT in IVUS post HTx was associated with poor outcomes up to 10 years. Early IVUS findings can be considered as surrogate endpoints for evaluating long-term outcomes in HTx clinical trials.
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Endoscopia Gastrointestinal , Obesidade , Humanos , Projetos Piloto , Obesidade/complicações , Endoscopia Gastrointestinal/métodos , Endoscopia Gastrointestinal/efeitos adversos , Feminino , Masculino , Pessoa de Meia-Idade , Oxigênio/administração & dosagem , Oxigênio/sangue , Máscaras/efeitos adversos , AdultoRESUMO
Importance: Heart failure (HF) affects more than 6 million adults in the US and more than 64 million adults worldwide, with 50% prevalence of depression. Patients and clinicians lack information on which interventions are more effective for depression in HF. Objective: To compare the effectiveness of behavioral activation psychotherapy (BA) vs antidepressant medication management (MEDS) on patient-centered outcomes inpatients with HF and depression. Design, Setting, and Participants: This pragmatic randomized comparative effectiveness trial was conducted from 2018 to 2022, including 1-year follow-up, at a not-for-profit academic health system serving more than 2 million people from diverse demographic, socioeconomic, cultural, and geographic backgrounds. Participant included inpatients and outpatients diagnosed with HF and depression, and data were analyzed as intention-to-treat. Data were analyzed from 2022 to 2023. Interventions: BA is an evidence-based manualized treatment for depression, promoting engagement in personalized pleasurable activities selected by patients. MEDS involves the use of an evidence-based collaborative care model with care managers providing coordination with patients, psychiatrists, and primary care physicians to only administer medications. Main Outcomes and Measures: The primary outcome was depressive symptom severity at 6 months, measured using the Patient Health Questionnaire 9-Item (PHQ-9). Secondary outcomes included physical and mental health-related quality of life (HRQOL), measured using the Short-Form 12-Item version 2 (SF-12); heart failure-specific HRQOL, measured using the Kansas City Cardiomyopathy Questionnaire; caregiver burden, measured with the Caregiver Burden Questionnaire for Heart Failure; emergency department visits; readmissions; days hospitalized; and mortality at 3, 6, and 12 months. Results: A total of 416 patients (mean [SD] age, 60.71 [15.61] years; 243 [58.41%] male) were enrolled, with 208 patients randomized to BA and 208 patients randomized to MEDS. At baseline, mean (SD) PHQ-9 scores were 14.54 (3.45) in the BA group and 14.31 (3.60) in the MEDS group; both BA and MEDS recipients experienced nearly 50% reduction in depressive symptoms at 3, 6, and 12 months (eg, mean [SD] score at 12 months: BA, 7.62 (5.73); P < .001; MEDS, 7.98 (6.06); P < .001; between-group P = .55). There was no statistically significant difference between BA and MEDS in the primary outcome of PHQ-9 at 6 months (mean [SD] score, 7.53 [5.74] vs 8.09 [6.06]; P = .88). BA recipients, compared with MEDS recipients, experienced small improvement in physical HRQOL at 6 months (mean [SD] SF-12 physical score: 38.82 [11.09] vs 37.12 [10.99]; P = .04), had fewer ED visits (3 months: 38% [95% CI, 14%-55%] reduction; P = .005; 6 months: 30% [95% CI, 14%-40%] reduction; P = .008; 12 months: 27% [95% CI, 15%-38%] reduction; P = .001), and spent fewer days hospitalized (3 months: 17% [95% CI, 8%-25%] reduction; P = .002; 6 months: 19% [95% CI, 13%-25%] reduction; P = .005; 12 months: 36% [95% CI, 32%-40%] reduction; P = .001). Conclusions and Relevance: In this comparative effectiveness trial of BA and MEDS in patients with HF experiencing depression, both treatments significantly reduced depressive symptoms by nearly 50% with no statistically significant differences between treatments. BA recipients experienced better physical HRQOL, fewer ED visits, and fewer days hospitalized. The study findings suggested that patients with HF could be given the choice between BA or MEDS to ameliorate depression. Trial Registration: ClinicalTrials.gov Identifier: NCT03688100.
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Depressão , Insuficiência Cardíaca , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Depressão/tratamento farmacológico , Qualidade de Vida , Psicoterapia , Antidepressivos/uso terapêutico , Insuficiência Cardíaca/terapiaRESUMO
BACKGROUND: This study aims to evaluate patient outcomes of simultaneous triple organ transplants, which may provide insight into optimal donor allocation while maximizing recipient benefit. METHODS: Triple organ transplants and their corollary dual organ transplants were identified using the United Network for Organ Sharing database. Triple organ transplants evaluated included heart-lung-kidney (n = 12) and heart-liver-kidney (n = 37). Heart-lung-kidney recipients were compared with heart-lung (n = 325), lung-kidney (n = 91), and heart-kidney (n = 2022) groups. Heart-liver-kidney recipients were compared with heart-liver (n = 451), liver-kidney (n = 10422), and heart-kidney (n = 2517) recipients. Patient survival outcomes were calculated using the Kaplan-Meier method and compared using log-rank tests. RESULTS: Patients undergoing triple organ transplants showed similar 10-year survival as their corresponding dual organ transplant cohorts. Patient survival estimate at 10 years for the heart-lung-kidney group was 45%, with no statistically significant difference in survival when compared with dual organ groups (P = .16). Survival estimates at 10 years for the heart-liver-kidney group was 49%, with no statistically significant difference in survival when compared with dual organ groups (P = .06). CONCLUSION: Despite the surgical burden of adding a third organ transplant, heart-liver-kidney and heart-lung-kidney have similar survival outcomes to dual organ equivalents and represent a reasonable allocation option in well-selected patients.
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Transplante de Coração , Transplante de Órgãos , Obtenção de Tecidos e Órgãos , Humanos , Estados Unidos , Transplante de Coração/efeitos adversos , Incidência , Estudos Retrospectivos , Transplante de Órgãos/efeitos adversos , Rim , Doadores de Tecidos , Sobrevivência de EnxertoRESUMO
BACKGROUND: The National Comprehensive Cancer Network recommends surgical resection for stage I small cell lung cancer (SCLC). Despite these recommendations and the curative potential of such surgery, many continue to underutilize surgery. Our aim is to investigate factors that contribute to underutilization of surgery for stage I SCLC. METHODS: The National Cancer Database was queried to identify patients with SCLC stage I-IV from 2004 to 2018. Staging was defined by the American Joint Committee on Cancer guidelines. Cochran-Armitage analysis was performed to analyze trends in surgical treatment for patients diagnosed with stage I SCLC. Multivariable logistic regression assessed relationships between patient factors and surgical treatment. RESULTS: A total of 296,583 patients were diagnosed with SCLC. Of the stage I patients (n = 13,003), only 29.4.% (n = 3823) underwent surgery. Trend analysis demonstrated increased frequency of surgical treatment for stage I SCLC over years 2004 to 2017, from 14.9% to 39.6% (P < .0001). Factors that were associated with underutilization of surgery for stage I SCLC include African American race, lower median income, nonprivate insurance or Medicare, community facility, and geographic regions other than the Northeast. CONCLUSIONS: Surgical treatment for stage I SCLC remains underutilized and our study identifies notable associated factors. The recognition of these factors may help patients overcome barriers to receiving recommended treatments, improve guideline adherence, and overall quality of care for stage I SCLC patients.
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Disparidades em Assistência à Saúde , Neoplasias Pulmonares , Estadiamento de Neoplasias , Pneumonectomia , Carcinoma de Pequenas Células do Pulmão , Humanos , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Carcinoma de Pequenas Células do Pulmão/cirurgia , Carcinoma de Pequenas Células do Pulmão/patologia , Masculino , Feminino , Idoso , Pneumonectomia/estatística & dados numéricos , Pneumonectomia/métodos , Estados Unidos , Pessoa de Meia-Idade , Disparidades em Assistência à Saúde/estatística & dados numéricos , Estudos RetrospectivosRESUMO
BACKGROUND: Pulmonary Arterial Hypertension (PAH) is a progressive condition with no cure. Even with pharmacologic advances, survival remains poor. Lung pathology on PAH therapies still shows impressive occlusive arteriolar remodelling and plexiform lesions. Cardiosphere-derived cells (CDCs) are heart-derived progenitor cells exhibiting anti-inflammatory and immunomodulatory effects, are anti -fibrotic, anti-oxidative and anti-apoptotic to potentially impact several aspects of PAH pathobiology. In preclinical trials CDCs reduced right ventricular (RV) systolic pressure, RV hypertrophy, pulmonary arteriolar wall thickness and inflammation. METHODS: The ALPHA study was a Phase 1a/b study in which CDCs were infused into patients with Idiopathic (I)PAH, Heritable (H) HPAH, PAH-connective tissue disease (CTD) and PAH-human immunodeficiency virus (HIV). The study was IRB approved and DSMB monitored. Phase 1a, was an open label study (n = 6). Phase 1b was a double-blind placebo-controlled study (n = 20) in which half received 100 million CDCs (the maximum feasible dose from manufacturing perspective) and half placebo (PLAC) infusions. Right heart catheterization (RHC) and cardiac MR imaging (cMR) were performed at baseline and at 4 months post infusion. Patients were followed over a year. FINDINGS: No short-term clinical safety adverse events (AE) were related to the IP, the primary outcome measure. There were no adverse hemodynamic, gas exchange, rhythm or other clinical events following infusion and in the 1st 23 h monitored in hospital. There were no long-term AEs over 12 months noted, including unrelated limited hospitalizations. No immunologic short or long-term AEs were noted. We examined exploratory outcomes across multiple domains to determine encouraging signals to motivate future advanced phase testing. Phase 1a data showed encouraging observations for both 50 and 100 million CDC doses. Several encouraging findings favouring CDCs (n = 16) compared to placebo (n = 10) were noted. On cMR, the RV end diastolic volume (RVEDV) and index (RVEDVI) decreased with CDCs with a rise in the PLAC group. The 6-min walk distance was increased 2 months post infusion in the CDC group compared with PLAC. With PLAC, diffusing capacity (DLCO) decreased at 4 months but was unchanged with CDCs. Serum creatinine decreased with CDCs at 4 months. Encouraging observations favouring CDCs were also noted for RV fractional area change on echo and RV ejection fraction (RVEF) on cMR at 4 months. No differences were observed for mean pulmonary artery pressures or pulmonary vascular resistance. Review of long-term data to 12 months showed continued decline in DLCO for the PLAC cohort at 6 months with no change through 12 months. By contrast, CDC subjects showed an unchanged DLCO over 12-months. For parameters exhibiting early encouraging exploratory findings in CDC subjects, no further improvement was noted in long-term follow up through 12 months. INTERPRETATION: Intravenous CDCs were safe in both the short and long term in PAH subjects and thus may be safe in larger cohorts, in line with our extensive track record of safety in clinical trials for other conditions. Further, CDCs exhibited encouraging exploratory findings across several domains. Repeat dosing (quarterly, over one year) of intravenous CDCs has been reported to yield highly significant sustained disease-modifying bioactivity in subjects with advanced Duchenne muscular dystrophy. Because only single CDC doses were used here, the findings represent a lower limit estimate of CDC's potential in PAH. Upcoming phase 2 studies would logically use a repeat dosing paradigm. FUNDING: California Institute for Regenerative Medicine (CIRM). Project Number: CLIN2-09444.
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Transplante de Células-Tronco Hematopoéticas , Hipertensão Arterial Pulmonar , Humanos , Coração , Volume SistólicoRESUMO
PURPOSE: Though the pathogenesis of benign prostatic hyperplasia is unclear, it was previously believed that increasing androgen levels contributed, though not all data support this idea. We tested if elevated serum testosterone or dihydrotestosterone were risk factors for lower urinary tract symptoms incidence in asymptomatic men and for lower urinary tract symptoms progression in symptomatic men. MATERIALS AND METHODS: A post hoc analysis of REDUCE was performed in 3009 asymptomatic men and in 2145 symptomatic men. REDUCE was a randomized trial of dutasteride for prostate cancer prevention in men with an elevated prostate-specific antigen and negative prestudy biopsy. We estimated multivariable adjusted hazard ratios and 95% confidence intervals using Cox models to test the association between quintiles of serum testosterone and dihydrotestosterone at baseline and lower urinary tract symptoms incidence and progression and tested for interaction by treatment arm (dutasteride vs placebo). RESULTS: In asymptomatic men, there was no evidence serum testosterone or dihydrotestosterone were related to lower urinary tract symptoms incidence (P = .9, P = .4). In symptomatic men, there was no evidence serum testosterone or dihydrotestosterone were related to lower urinary tract symptoms progression (P = .9, P = .7). Results were similar in both placebo and dutasteride arms (all P interaction ≥ .3). CONCLUSIONS: In REDUCE, higher serum testosterone and higher serum dihydrotestosterone were not associated with either lower urinary tract symptoms incidence in asymptomatic men or lower urinary tract symptoms progression in symptomatic men. These data do not support the hypothesis that serum androgens in middle-aged men are associated with lower urinary tract symptoms.
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Sintomas do Trato Urinário Inferior , Hiperplasia Prostática , Humanos , Masculino , Pessoa de Meia-Idade , Di-Hidrotestosterona/uso terapêutico , Dutasterida/uso terapêutico , Incidência , Sintomas do Trato Urinário Inferior/etiologia , Hiperplasia Prostática/complicações , Testosterona , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Physical restraints are used in the emergency department (ED) for agitated patients to prevent self-harm and protect staff. Prior studies identified associations between sociodemographic factors and ED physical restraints use. OBJECTIVES: The primary objective was to compare characteristics of ED patients receiving physical restraints for violent and nonviolent indications vs. patients who were not restrained. The secondary objective was to compare rates of restraint use among ED providers. METHODS: This was a single-center cross-sectional study of adult ED patients from March 2019 to February 2021. Factors compared across groups were age over 50 years, gender, race, ethnicity, insurance, housing, primary language, Emergency Severity Index, time of arrival, mode of arrival, chief complaint, and medical admission. Odds ratios were reported. Rates of emergency physician restraint orders were compared using the chi-square test. RESULTS: Restraints were used in 1228 (0.9%) visits. Younger age, male gender, "unknown" ethnicity, self-pay or "other" nonprivate insurance, homelessness, arrival by first responders, and medical hospitalization were associated with increased odds of restraint. Black patients had lower odds of any restraint than White patients (odds ratio 0.93; 95% confidence interval 0.79-1.09) and higher odds of violent restraint than White patients, although not significant (odds ratio 1.55; 95% confidence interval 0.95-2.54). ED providers had significant differences in total and violent restraint use (p-values < 0.0001 and 0.0003, respectively). CONCLUSION: At this institution, certain sociodemographic characteristics were associated with receiving both types of physical restraint. Emergency physicians also differed in restraint-ordering practice. Further investigation is needed to understand the influence of implicit bias on ED restraint use.
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Introduction: Image-guided percutaneous microwave ablation (MWA) is becoming a more common treatment option for patients with primary and metastatic lung malignancies. Nevertheless, there is limited literature on the safety and efficacy of MWA compared with standard-of-care therapy, including surgical resection and radiation. This study will report the long-term outcomes after MWA for pulmonary malignancies and investigate the factors related to efficacy, including lesion size, location, and ablation power. Methods: Retrospective single-center study analyzing 93 patients who underwent percutaneous MWA for primary or metastatic lung malignancies. Outcomes included immediate technical success, local tumor recurrence, overall survival, disease-specific survival, and complications. Results: At a single institution, 190 lesions (81 primary and 109 metastatic) were treated in 93 patients. Immediate technical success was achieved in all cases. Freedom from local recurrence was 87.6%, 75.3%, and 69.2% and overall survival was 87.7%, 76.2%, and 74.3% at 1 year, 2 years, and 3 years, respectively. Disease-specific survival was 92.6%, 81.8%, and 81.8%. The most common complication was pneumothorax, which occurred in 54.7% (104 of 190) of procedures, with 35.2% (67 of 190) requiring a chest tube. No life-threatening complications occurred. Conclusions: Percutaneous MWA seems safe and effective for treatment of primary and metastatic lung malignancies and should be considered for patients with limited metastatic burden and lesions less than 3 cm in size.
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BACKGROUND: A subset of chronic anal fissures beget focal infection, leading to concomitant fistula. The optimal management of fissure-associated fistula is unknown. OBJECTIVE: This study aimed to characterize healing rates and effects of fistulotomy in fissure-associated fistula. DESIGN: Retrospective study. SETTING: Urban tertiary center. PATIENTS: Adults who underwent fistulotomy for a fistula associated with a chronic anal fissure were included in the study. However, those with Crohn's disease, a history of lateral internal sphincterotomy, and a fistula not amenable to fistulotomy were excluded. INTERVENTIONS: Patients were managed with fistulotomy. Fissures were otherwise managed conservatively with a step-up approach. MAIN OUTCOME MEASURES: The primary end point was healing, defined as resolution of symptoms and both fistula and fissure wounds within 1 year. Subgroup analysis compared those who underwent subcutaneous fistulotomy (group A) with those who underwent fistulotomy involving anal sphincter fibers (group B). RESULTS: Twenty-four of 38 patients (63%) healed with a median overall follow-up of 6.6 months (4.2-14.1). The overall median time to healing was 4.4 months (2.2-6.0). No clinical or pathologic factors predicted healing. In subgroup analysis, overall subcutaneous fistulotomy healing rates were nonstatically lower at 46% (6/13) compared to fistulotomy involving anal sphincter fibers at 72% (18/25; p = 0.16). There was no difference in time to healing (subcutaneous fistulotomy, 6.7 mo [5.2-8.4] vs fistulotomy involving sphincter, 5.1 mo [2.1-7.0]; p = 0.36). LIMITATIONS: The limitations include treatment bias, with increased utilization of chemical sphincter-relaxing agents in those who did not heal. Findings are not applicable to complex fistulas, Crohn's disease, or atypical fissures. CONCLUSIONS: Patients presenting with chronic fissure and associated subcutaneous, intersphincteric, or low transphincteric fistula are successfully managed with fistulotomy. Patients with a subcutaneous fistula tract exhibited nonstatistically significantly lower rates of healing. See Video Abstract at http://links.lww.com/DCR/C145 . EFICACIA DE LA DIVISIN ESFINTRICA DURANTE LA FISTULOTOMA EN CASOS DE FSTULA ASOCIADA A FISURA ANAL: ANTECEDENTES: Ciertos subgrupos de fisuras anales crónicas ocasionan infección localizada, induciendo la aparición de una fístula anal concomitante. Se desconoce el manejo óptimo de la fístula concomitante a una fisura anal.OBJETIVO: Se trata de caracterizar las tasas de curación y el efecto de la fistulotomía en el tratamiento de la fístula concomitante a la fisura anal.DISEÑO: Estudio retrospectivo.EMPLAZAMIENTO: Centro terciario urbano.PACIENTES: Adultos sometidos a fistulotomía por una fístula concomitante a una fisura anal crónica. Se excluyeron la enfermedad de Crohn, el antecedente de una esfinterotomía lateral interna y las fístulas no susceptibles de fistulotomía.INTERVENCIONES: Los pacientes fueron manejados con una fistulotomía clasica. Por lo demás, las fisuras se trataron de forma conservadora con un enfoque médico escalonado.PRINCIPALES MEDIDAS DE RESULTADO: El criterio principal de valoración fué la cura definitiva, determinada como la resolución completa de los síntomas y de las heridas tanto de la fístula como de la fisura en el plazo de un año. El análisis de los subgrupos comparó los que se sometieron a una fistulotomía subcutánea (grupo A) versus una fistulotomía que involucró las fibras del esfínter anal interno (grupo B).RESULTADOS: 24/38 pacientes (63%) curaron con una mediana de seguimiento global de 6,6 meses (4,2-14,1). El tiempo medio general de curación fue de 4,4 meses (2,2-6,0). Ningún factor clínico o patológico predijo la cura. En el análisis de subgrupos, las tasas generales de cura de la fistulotomía subcutánea no fueron estadísticamente más bajas de 46 % (6/13) comparados con la fistulotomía que involucró las fibras del esfínter anal interno en 72 % (18/25; p = 0,16). No hubo diferencia en el tiempo de cicatrización [fistulotomía subcutánea 6,7 meses (5,2-8,4) conparada a la fistulotomía y esfínterotomía parcial interna a 5,1 meses (2,1-7,0); p = 0,36].LIMITACIONES: Sesgo del tratamiento, con mayor utilización de agentes químicos relajantes de la musculatura esfínteriana en aquellos pacientes que no sanaron. No aplicable a fístulas complejas, enfermedad de Crohn o fisuras atípicas.CONCLUSIÓNES: Los pacientes que presentan fisura crónica y fístula subcutánea, inter-esfintérica o trans-esfintérica baja concomitante se manejan con éxito con una fistulotomía. Los pacientes con un trayecto de fístula subcutánea exhibieron tasas de curación más bajas y no estadísticamente significativas. Consulte Video Resumen en http://links.lww.com/DCR/C145 . (Traducción-Dr. Xavier Delgadillo ).
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Doença de Crohn , Fissura Anal , Fístula Retal , Adulto , Humanos , Estudos Retrospectivos , Doença de Crohn/complicações , Canal Anal , Fístula Retal/complicaçõesRESUMO
BACKGROUND: Perinatal mood and anxiety disorders encompass a range of mental health disorders that occur during pregnancy and up to 1 year postpartum, affecting approximately 20% of women. Traditional risk factors, such as a history of depression and pregnancy complications including preeclampsia, are known. Their predictive utility, however, is not specific or sensitive enough to inform clinical decision-making or prevention strategies for perinatal mood and anxiety disorders. Better diagnostic and prognostic models are needed for early identification and referral to treatment. OBJECTIVE: This study aimed to determine if a panel of novel third-trimester plasma protein biomarkers in pregnant women can be used to identify those who have a high predisposed risk for perinatal mood and anxiety disorders within 3 months postpartum. STUDY DESIGN: We studied 52 women (n=34 with a risk for perinatal mood and anxiety disorders and n=18 controls) among whom mental health screening was conducted at 2 time points, namely in the third trimester and again at 3 months postdelivery. An elevated perinatal mood and anxiety disorder risk was identified by screening individuals with above-validated cutoffs for depression (Edinburgh Postnatal Depression Scale ≥12), anxiety (Overall Anxiety Severity and Impairment Scale ≥7), and/or posttraumatic stress disorder (Impact of Events Scale >26) at both time points. Plasma samples collected in the third trimester were screened using the aptamer-based SomaLogic SomaScan proteomic assay technology to evaluate perinatal mood and anxiety disorder-associated changes in the expression of 1305 protein analytes. Ingenuity Pathway Analysis was conducted to highlight pathophysiological relationships between perinatal mood and anxiety disorder-specific proteins found to be significantly up- or down-regulated in all subjects with perinatal mood and anxiety disorder and in those with perinatal mood and anxiety disorders and no preeclampsia. RESULTS: From a panel of 53 significant perinatal mood and anxiety disorder-associated proteins, a unique 20-protein signature differentiated perinatal mood and anxiety disorder cases from controls in a principal component analysis (P<.05). This protein signature included NCAM1, NRCAM, and NTRK3 that converge around neuronal signaling pathways regulating axonal guidance, astrocyte differentiation, and maintenance of GABAergic neurons. Interestingly, when we restricted the analysis to subjects without preeclampsia, a 30-protein signature differentiated perinatal mood and anxiety disorder cases from all controls without overlap on the principal component analysis (P<.001). In the nonpreeclamptic perinatal mood and anxiety disorder group, we observed increased expression of proteins, such as CXCL11, CXCL6, MIC-B, and B2MG, which regulate leucocyte migration, inflammation, and immune function. CONCLUSION: Participants with perinatal mood and anxiety disorders had a unique and distinct plasma protein signature that regulated a variety of neuronal signaling and proinflammatory pathways. Additional validation studies with larger sample sizes are needed to determine whether some of these molecules can be used in conjunction with traditional risk factors for the early detection of perinatal mood and anxiety disorders.
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Depressão Pós-Parto , Complicações na Gravidez , Feminino , Gravidez , Humanos , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/psicologia , Depressão/diagnóstico , Proteômica , Ansiedade/complicações , Complicações na Gravidez/psicologia , Biomarcadores , Depressão Pós-Parto/diagnósticoRESUMO
BACKGROUND: Noninvasive telemonitoring and nurse telephone coaching (NTM-NTC) is a promising postdischarge strategy in heart failure (HF). Comorbid conditions and disease burden influence health outcomes in HF, but how comorbidity burden modulates the effectiveness of NTM-NTC is unknown. This study aims to identify patients with HF who may benefit from postdischarge NTM-NTC based on their burden of comorbidity. METHODS AND RESULTS: In the Better Effectiveness After Transition - Heart Failure trial, patients hospitalized for acute decompensated HF were randomized to postdischarge NTM-NTC or usual care. In this secondary analysis of 1313 patients with complete data, comorbidity burden was assessed by scoring complication and coexisting diagnoses from index admissions. Clinical outcomes included 30-day and 180-day readmissions, mortality, days alive, and combined days alive and out of the hospital. Patients had a mean of 5.7 comorbidities and were stratified into low (0-2), moderate (3-8), and high comorbidity (≥9) subgroups. Increased comorbidity burden was associated with worse outcomes. NTM-NTC was not associated with readmission rates in any comorbidity subgroup. Among high comorbidity patients, NTM-NTC was associated with significantly lower mortality at 30 days (hazard ratio 0.25, 95% confidence interval 0.07-0.90) and 180 days (hazard ratio 0.51, 95% confidence interval 0.27-0.98), as well as more days alive (160.1 vs 140.3, Pâ¯=â¯.029) and days alive out of the hospital (152.0 vs 133.2, Pâ¯=â¯.044) compared with usual care. CONCLUSIONS: Postdischarge NTM-NTC improved survival among patients with HF with a high comorbidity burden. Comorbidity burden may be useful for identifying patients likely to benefit from this management strategy.
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Insuficiência Cardíaca , Tutoria , Humanos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/terapia , Readmissão do Paciente , Alta do Paciente , Assistência ao Convalescente , Comorbidade , TelefoneRESUMO
BACKGROUND: Invasive lobular carcinoma (ILC) is associated with high re-excision rates following breast-conserving surgery (BCS). The correlation between lesion size on different imaging modalities and final tumor size has not been well characterized. METHODS: A prospective database of patients with stage I-III breast cancer undergoing BCS between 2006 and 2016 was reviewed. Pearson correlation analysis was used to correlate tumor size on breast imaging to final pathology. RESULTS: Of these, 111 patients with ILC were identified. Mean lesion size was 1.93 cm for MMG, 1.61 cm for US, and 2.51 cm for MRI. Mean tumor size on surgical excision was 2.64 cm. The correlation coefficient between pathology and the different imaging modalities were as follows: MMG .17, US 0.37, and MRI .58. Actual tumor size was underestimated by 1 cm in 27.1% of MMGs, 50% of USs, and in 13.3% of MRIs. 38 patients (34.2%) underwent re-excision. No differences in re-excision rates were noted in patients with and without MRI, 30.3% vs 40.0%, respectively (P = .31). CONCLUSION: While MRI provides a better estimate of tumor size than MMG and US, the size of the tumor on imaging only weakly correlated with pathology. The use of MRI does not decrease re-excision rates.
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Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Lobular , Humanos , Feminino , Carcinoma Lobular/diagnóstico por imagem , Carcinoma Lobular/cirurgia , Carcinoma Lobular/patologia , Estudos Retrospectivos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Mama/diagnóstico por imagem , Mama/cirurgia , Mama/patologia , Mastectomia Segmentar , Imageamento por Ressonância Magnética/métodos , Carcinoma Ductal de Mama/cirurgiaRESUMO
Antibody-mediated rejection (AMR) is the major cause of graft loss in kidney transplant recipients. The Banff classification defines two classes of AMR, active and chronic active but over time this classification has become increasingly complex. To simplify the approach to AMR, we developed activity and chronicity indices based on kidney transplant biopsy findings and examined their association with graft survival in 147 patients with active or chronic active AMR, all of whom had donor-specific antibodies and were treated for AMR. The activity index was determined as the sum of Banff glomerulitis (g), peritubular capillaritis (ptc), arteritis (v) and C4d scores, with a maximum score of 12. The chronicity index was the sum of interstitial fibrosis (ci), tubular atrophy (ct), chronic vasculopathy (cv), and chronic glomerulopathy (cg) scores, the latter doubled, with a maximum score of 15. While the activity index was generally not associated with graft loss, the chronicity index was significantly associated with graft loss with an optimal threshold value of 4 or greater for predicting graft loss. The association of the chronicity index of 4 or greater with graft loss was independent of other parameters associated with graft loss, including the estimated glomerular filtration rate at the time of biopsy, chronic active (versus active) AMR, AMR with de novo (versus persistent/rebound) donor-specific antibodies, Banff (g+ptc) scores, concurrent T cell-mediated rejection and donor-specific antibody reduction post-biopsy. The association of the chronicity index of 4 or greater with graft loss was confirmed in an independent cohort of 61 patients from Necker Hospital, Paris. Thus, our findings suggest that the chronicity index may be valuable as a simplified approach to decision-making in patients with AMR.
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Glomerulonefrite , Nefropatias , Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Rejeição de Enxerto , Isoanticorpos , Sobrevivência de Enxerto , BiópsiaRESUMO
BACKGROUND: Heart transplantation (HTx) is an established therapeutic option for patients with advanced heart failure who are refractory to conventional guideline-directed treatments. This study aimed to reassess whether intravascular ultrasound variables could predict adverse events after HTx in the modern era. METHODS: One hundred primary HTx recipients with available serial intravascular ultrasound examination results of the left anterior descending artery 4-8 wk and 1 y after HTx were enrolled, with an average follow-up duration of 5.7 y. The primary endpoint was a composite of all-cause death, nonfatal major adverse cardiac events, and angiographic cardiac allograft vasculopathy. RESULTS: Forty-three patients developed primary endpoints. The baseline maximal intimal thickness was independently associated with the primary endpoint (hazard ratio, 8.24; 95% confidential interval [CI], 3.21-21.21; P < 0.001), and the optimal cutoff value was 0.64 mm. A change in the plaque atheroma volume in a proximal 20-mm segment from the left anterior descending artery bifurcation >1.05 mm 3 /mm (hazard ratio, 2.75; 95% CI, 1.28-5.89; P = 0.009) and a change in the first-year maximal intimal thickness >0.27 mm (hazard ratio, 2.63; 95% CI, 1.05-6.56; P = 0.04) were independent predictors of the primary endpoint 1 y after intravascular ultrasonography. CONCLUSIONS: The aforementioned important clinical implications of intravascular ultrasound parameters are useful predictors of outcomes, which may be considered endpoints in modern clinical HTx trials.
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Cardiopatias , Transplante de Coração , Placa Aterosclerótica , Humanos , Cardiopatias/etiologia , Placa Aterosclerótica/complicações , Ultrassonografia , Transplante de Coração/efeitos adversos , Ultrassonografia de IntervençãoRESUMO
CONTEXT: Preclinical studies show seliciclib (R-roscovitine) suppresses neoplastic corticotroph proliferation and pituitary adrenocorticotrophic hormone (ACTH) production. OBJECTIVE: To evaluate seliciclib as an effective pituitary-targeting treatment for patients with Cushing disease (CD). METHODS: Two prospective, open-label, phase 2 trials, conducted at a tertiary referral pituitary center, included adult patients with de novo, persistent, or recurrent CD who received oral seliciclib 400 mg twice daily for 4 consecutive days each week for 4 weeks. The primary endpoint in the proof-of-concept single-center study was normalization of 24-hour urinary free cortisol (UFC; ≤ 50 µg/24 hours) at study end; in the pilot multicenter study, primary endpoint was UFC normalization or ≥ 50% reduction in UFC from baseline to study end. RESULTS: Sixteen patients were consented and 9 were treated. Mean UFC decreased by 42%, from 226.4 ± 140.3 µg/24 hours at baseline to 131.3 ± 114.3 µg/24 hours by study end. Longitudinal model showed significant UFC reductions from baseline to each treatment week. Three patients achieved ≥ 50% UFC reduction (range, 55%-75%), and 2 patients exhibited 48% reduction; none achieved UFC normalization. Plasma ACTH decreased by 19% (P = 0.01) in patients who achieved ≥ 48% UFC reduction. Three patients developed grade ≤ 2 elevated liver enzymes, anemia, and/or elevated creatinine, which resolved with dose interruption/reduction. Two patients developed grade 4 liver-related serious adverse events that resolved within 4 weeks of seliciclib discontinuation. CONCLUSION: Seliciclib may directly target pituitary corticotrophs in CD and reverse hypercortisolism. Potential liver toxicity of seliciclib resolves with treatment withdrawal. The lowest effective dose requires further determination.
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Hipersecreção Hipofisária de ACTH , Adulto , Humanos , Hipersecreção Hipofisária de ACTH/tratamento farmacológico , Roscovitina/uso terapêutico , Estudos Prospectivos , Hidrocortisona , Hormônio AdrenocorticotrópicoRESUMO
BACKGROUND: The role of angiotensin II type 1 receptor antibodies (AT1R-Ab) in pediatric renal transplantation is unclear. Here, we evaluated pre-transplant AT1R-Ab on transplant outcomes in the first 5 years. Secondary analysis compared pre-transplant AT1R-Ab levels by age. METHODS: Thirty-six patients, 2-20 years old, were divided into two groups: pre-transplant AT1R-Ab- (<17 U/ml; n = 18) and pre-transplant AT1R-Ab+ (≥17 U/ml; n = 18). eGFR was determined at 6-month, 1-, 2-, and 4-year post-transplant. Allograft biopsies were performed in the setting of strong HLA-DSA (MFI > 10 000), AT1R-Ab ≥17 U/ml, and/or elevated creatinine. RESULTS: Mean age in pre-transplant AT1R-Ab- was 13.3 years vs. 11.0 in pre-transplant AT1R-Ab+ (p = 0.16). At 6 months, mean eGFR was 111.3 ml/min/1.73 m2 in pre-transplant AT1R-Ab- vs. 100.2 in pre-transplant AT1R-Ab + at 1 year, 103.6 ml/min/1.73 m2 vs. 100.5; at 2 years, 98.9 ml/min/1.73 m2 vs. and 93.7; at 4 years, 72.6 ml/min/1.73 m2 vs. 80.9. 11/36 patients had acute rejection (6 in pre-transplant AT1R-Ab-, 5 in pre-transplant AT1R-Ab + ). There was no difference in rejection rates. All 6 subjects with de novo HLA-DSA and AT1R-Ab ≥17 U/ml at the time of biopsy experienced rejection. Mean age in those with the AT1R-Ab ≥40 U/ml was 10.0 years vs. 13.2 in those <40 U/ml (p = 0.07). CONCLUSION: In our small cohort, pre-transplant AT1R-Ab ≥17 U/ml was not associated with reduced graft function or rejection. The pathogenicity of pre-transplant AT1R-Ab in pediatric kidney transplantation requires further investigation.
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Anticorpos , Rejeição de Enxerto , Transplante de Rim , Receptor Tipo 1 de Angiotensina , Adolescente , Adulto , Criança , Pré-Escolar , Humanos , Adulto Jovem , Anticorpos/sangue , Estudos de Coortes , Rejeição de Enxerto/sangue , Rejeição de Enxerto/imunologia , Antígenos HLA/imunologia , Rim/patologia , Receptor Tipo 1 de Angiotensina/imunologiaRESUMO
Although postoperative diet modification, exercise, and regular dietitian and surgeon follow-up are often recommended after bariatric surgery (BS), their impact on weight loss is unclear. A Retrospective chart review was conducted for patients who received sleeve gastrectomy or Roux-en-Y gastric bypass (RYGB) between August 2000 and November 2017 with telephone follow-up. Multivariable logistic regression models were used for analyses. There were 514 patients included in our study. Most were female (76.3%), mean age was 46.9 years (Standard Deviation [SD] = 11.8), and mean weight loss was 11.6 (SD = 6.5) BMI points at a mean follow-up of 7 years (SD = 4.3). Current surgeon follow-up OR = 2.08 (P < .01) was positively associated with postoperative weight loss, while current dietitian follow-up=OR .41 (P < .01) was negatively associated. Current weight loss supplement use OR = .45 (P = .03) was associated with reduced willingness to undergo surgery again. Increasing preoperative BMI OR = 1.06 (P = .04) and increasing age OR = 1.04 (P = .02) were associated with improved quality of life (QoL) due to BS. Lack of surgeon follow-up and regular dietician consultation was associated with suboptimal weight loss after BS. Older age was positively associated with improved QoL, while current weight loss supplement use was associated with lower likelihood of undergoing surgery again, both independent of weight loss.
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Cirurgia Bariátrica , Derivação Gástrica , Nutricionistas , Obesidade Mórbida , Cirurgiões , Feminino , Seguimentos , Gastrectomia , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/cirurgia , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento , Redução de PesoRESUMO
INTRODUCTION: Inadequate pain control frequently extends length of stay (LOS) and costs for patients undergoing mastectomy with implant-based reconstruction (IBR). We sought to examine the effects of Paravertebral blocks (PVB) and liposomal bupivacaine (LB) and compare LOS, pain scores and costs of hospitalization. METHODS: Prospective database review of patients undergoing mastectomy with IBR was performed. RESULTS: 541 patients were identified. 51/491 (9.4%) received PVB and 50 (9.2%) received LB. LOS in the PVB group was significantly less than that of the no block (NB) group (1 [1-2] days PVB vs 3 [2-4] days NB (p < 0.0001), but was not different from the LB group (1 [1-2] days LB, p = 0.23). PVB patients had lower PACU pain scores compared to NB patients (3.2 ± 2.9 PVB vs 5.7 ± 2.6 NB, p < 0.0001), but similar PACU pain scores to LB patients (4.1 ± 2.3). Patients who received PVB had higher total costs compared to NB patients ($27148±$7053 PVB vs $23113 ± 6860 NB, p = 0.003) but similar to LB patients ($26183 ± $3761). CONCLUSION: PVB and LB are associated with shorter LOS and lower pain scores compared to NB.
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Neoplasias da Mama , Mastectomia , Anestésicos Locais , Bupivacaína , Feminino , Hospitais , Humanos , Dor Pós-Operatória , Estudos RetrospectivosRESUMO
INTRODUCTION: In 2020, a working group of 13 renal pathologists published consensus definitions for 47 individual glomerular lesions found on light microscopy (LM) and 47 glomerular lesions and 9 normal structures found on electron microscopy (EM). METHODS: To test the impact of these definitions on identification of these lesions and structures, 2 surveys were circulated to all members of the Renal Pathology Society (RPS), each having 32 images (19 LM, 13 EM) and accompanying questions with 5 multiple-choice answers, one being the consensus choice of the working group. The first survey (survey 1 [S1]), answered by 297 RPS members, was sent in September 2020, before publication of the consensus definitions. The second (survey 2 [S2]), with images of the same lesions and structures (but not the same images) and the same questions and multiple choices in different order, was sent in April 2020, 5 months after the publication of the definitions. RESULTS: S2 was taken by 181 RPS members; 64% also took S1 and 61% reported having read the definitions paper (def. paper). Mean agreement with the consensus answers increased modestly between the 2 surveys (65.2% vs. 72.0%, P = 0.097); the increase was greater and significant when only respondents to S2 who read the def. paper were considered (65.2% vs. 74.8%, P = 0.026). Furthermore, in S2 agreement with consensus answers was greater among respondents who read this paper versus those who did not (66.9% vs. 74.8%, P < 0.0001). CONCLUSIONS: Publication of the consensus definitions modestly improved interobserver agreement in identification of glomerular lesions.