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1.
Acad Med ; 99(2): 183-191, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37976531

RESUMO

PURPOSE: To examine the relationship between the Association of American Medical Colleges (AAMC) Professional Readiness Exam (PREview) scores and other admissions data, group differences in mean PREview scores, and whether adding a new assessment tool affected the volume and composition of applicant pools. METHOD: Data from the 2020 and 2021 PREview exam administrations were analyzed. Two U.S. schools participated in the PREview pilot in 2020 and 6 U.S. schools participated in 2021. PREview scores were paired with data from the American Medical College Application Service (undergraduate grade point averages [GPAs], Medical College Admission Test [MCAT] scores, race, and ethnicity) and participating schools (interview ratings). RESULTS: Data included 19,525 PREview scores from 18,549 unique PREview examinees. Correlations between PREview scores and undergraduate GPAs ( r = .16) and MCAT scores ( r = .29) were small and positive. Correlations between PREview scores and interview ratings were also small and positive, ranging between .09 and .14 after correcting for range restriction. Small group differences in mean PREview scores were observed between White and Black or African American and White and Hispanic, Latino, or of Spanish origin examinees. The addition of the PREview exam did not substantially change the volume or composition of participating schools' applicant pools. CONCLUSIONS: Results suggest the PREview exam measures knowledge of competencies that are distinct from those measured by other measures used in medical school admissions. Observed group differences were smaller than group differences observed with traditional academic assessments and evaluations. The addition of the PREview exam did not substantially change the overall volume of applications or the proportions of out-of-state, underrepresented in medicine, or lower socioeconomic status applicants. While more research is needed, these results suggest the PREview exam may provide unique information to the admissions process without adversely affecting applicant pools.


Assuntos
Critérios de Admissão Escolar , Estudantes de Medicina , Humanos , Julgamento , Faculdades de Medicina , Teste de Admissão Acadêmica
2.
bioRxiv ; 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37609209

RESUMO

Molecular engineering of biocatalysts has revolutionized complex synthetic chemistry and sustainable catalysis. Here, we show that it is also possible to use engineered biocatalysts to reprogram signal transduction in human cells. More specifically, we manipulate cellular hypoxia (low O2) signaling by engineering the gas-delivery tunnel of prolyl hydroxylase 2 (PHD2), an iron-dependent enzymatic O2 sensor. Using computational modeling and rational protein design techniques, we resolve PHD2's gas tunnel and critical residues therein that limit the flow of O2 to PHD2's catalytic core. Systematic modification of these residues open the constriction topology of PHD2's gas tunnel with the most effectively designed mutant displaying 11-fold enhanced hydroxylation efficiency. Furthermore, transfection of plasmids that express these engineered PHD2 mutants in HEK-293T cells reveal significant reduction in the levels of hypoxia inducible factor (HIF-1α) even under hypoxic conditions. Our studies reveal that activated PHD2 mutants can reprogram downstream HIF pathways in cells to simulate physiological O2-like conditions despite extreme hypoxia and underscores the potential of engineered biocatalysts in controlling cellular function.

3.
Am J Clin Exp Urol ; 11(2): 185-193, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37168940

RESUMO

Extramural venous invasion (EMVI) recognized on magnetic resonance imaging (MRI) is an unequivocal biomarker for detecting adverse outcomes in rectal cancer: however it has not yet been explored in the area of bladder cancer. In this study, we assessed the feasibility of identifying EMVI findings on MRI in patients with bladder cancer and its avail in identifying adverse pathology. In this single-institution retrospective study, the MRI findings inclusive of EMVI was described in patients with bladder cancer that had available imaging between January 2018 and June 2020. Patient demographic and clinical information were retrieved from our electronic medical records system. Histopathologic features frequently associated with poor outcomes including lymphovascular invasion (LVI), variant histology, muscle invasive bladder cancer (MIBC), and extravesical disease (EV) were compared to MRI-EMVI. A total of 38 patients were enrolled in the study, with a median age of 73 years (range 50-101), 76% were male and 23% were females. EMVI was identified in 23 (62%) patients. There was a significant association between EMVI and MIBC (OR = 5.30, CI = 1.11-25.36; P = 0.036), and extravesical disease (OR = 17.77, CI = 2.37-133; P = 0.005). We found a higher probability of presence of LVI and histologic variant in patients with EMVI. EMVI had a sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) of 90%, 73%, 94% and 63% respectively in detecting extravesical disease. Our study suggests, EMVI may be a useful biomarker in bladder cancer imaging, is associated with adverse pathology, and could be potentially integrated in the standard of care with regards to MRI reporting systems. A larger study sample size is further warranted to assess feasibility and applicability.

4.
JAMA Netw Open ; 6(3): e231922, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36881409

RESUMO

Importance: Preference signaling is a new initiative in the residency application process that has been adopted by 17 specialties that include more than 80% of applicants in the 2023 National Resident Matching cycle. The association of signals with interview selection rate across applicant demographics has not been fully examined. Objective: To assess the validity of survey-based data on the association of preference signals with interview offers and describe the variation across demographic groups. Design, Setting, and Participants: This cross-sectional study examined the interview selection outcomes across demographic groups for applications with and without signals in the 2021 Otolaryngology National Resident Matching cycle. Data were obtained from a post-hoc collaboration between the Association of American Medical Colleges and the Otolaryngology Program Directors Organization evaluating the first preference signaling program used in residency application. Participants included otolaryngology residency applicants in the 2021 application cycle. Data were analyzed from June to July 2022. Exposures: Applicants were provided the option of submitting 5 signals to otolaryngology residency programs to indicate specific interest. Signals were used by programs when selecting candidates to interview. Main Outcomes and Measures: The main outcome of interest was the association of signaling with interview selection. A series of logistic regression analyses were conducted at the individual program level. Each program within the 3 program cohorts (overall, gender, and URM status) was evaluated with 2 models. Results: Of 636 otolaryngology applicants, 548 (86%) participated in preference signaling, including 337 men (61%) and 85 applicants (16%) who identified as underrepresented in medicine, including American Indian or Alaska Native; Black or African American; Hispanic, Latino, or of Spanish origin; or Native Hawaiian or other Pacific Islander. The median interview selection rate for applications with a signal (48% [95% CI, 27%-68%]) was significantly higher than for applications without a signal (10% [95% CI, 7%-13%]). No difference was observed in median interview selection rates with or without signals when comparing male (46% [95% CI, 24%-71%] vs 7% [95% CI, 5%-12%]) and female (50% [95% CI, 20%-80%] vs 12% [95% CI, 8%-18%]) applicants or when comparing applicants who identified as URM (53% [95% CI, 16%-88%] vs 15% [95% CI, 8%-26%]) with those who did not identify as URM (49% [95% CI, 32%-68%] vs 8% [95% CI, 5%-12%]). Conclusions and Relevance: In this cross-sectional study of otolaryngology residency applicants, preference signaling was associated with an increased likelihood of applicants being selected for interview by signaled programs. This correlation was robust and present across the demographic categories of gender and self-identification as URM. Future research should explore the associations of signaling across a broad range of specialties and the associations of signals with inclusion and position on rank order lists and match outcomes.


Assuntos
Internato e Residência , Otolaringologia , Humanos , Feminino , Masculino , Estudos Transversais , Demografia
5.
Prostate Int ; 11(1): 20-26, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36910904

RESUMO

Background: Holmium enucleation of the prostate (HoLEP) is becoming the gold standard for the treatment of benign prostatic hyperplasia (BPH). Our objective was to identify predictors of 30-day readmission and the impact of same-day discharge after HoLEP. Methods: Using NSQIP data from 2011 to 2019, we identified men who underwent HoLEP for the treatment of BPH. We compared patients based on time of discharge and readmission status. We used multivariable logistic regression analysis (MLRA) to identify independent factors associated with 30-day readmission. Results: A total of 3,489 patients met inclusion criteria with 833 (23.88%) being discharged within 24 hours and 2,656 (76.12%) discharged after 24 hours. There were 158 (4.53%) 30-day readmissions, mostly due to hematuria and urinary tract infection. Patients being readmitted were older (72 vs. 70 years old, P = 0.001), were more likely to have preoperative anemia (36.7% vs. 23.1%; P < 0.001), chronic kidney disease (29.7% vs. 19.7%; P < 0.001), bleeding disorder (10.8% vs. 2.8%; P < 0.001), higher American Society of Anesthesiologists (ASA) scores (≥3: 70.3% vs. 46.7%; P < 0.001) and a higher frailty burden (5-item modified frailty index [5i-mFI] ≥ 2: 36.1% vs. 19.1%; P < 0.001) compared to their counterparts. Factors independently associated with 30-day readmission were bleeding disorder (OR 2.89; 95% CI 1.63-5.11; P < 0.001), 5i-mFI ≥ 2 (OR 1.67; 95% CI 1.03-2.71; P = 0.038) and an ASA score ≥3 (OR 1.80; 95% CI 1.21-2.70; P = 0.004); however, same-day discharge was not found to be a significant predictor of 30-day readmissions. Conclusion: The overall readmission rate after HoLEP is low. Patients discharged within 24 hours have similar rates of readmission compared to patients discharged after 24 hours. We found bleeding disorder, frailty burden, and ASA score to be independent predictors of 30-day readmission.

6.
J Heart Lung Transplant ; 42(4): 480-487, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36464610

RESUMO

BACKGROUND: Blood group O candidates have lower lung transplantation rates despite having the most common blood group. We postulated that waitlist outcomes among these candidates and those with other blood types vary with disease severity and lung allocation score (LAS). METHODS: We performed a retrospective cohort study of 32,772 waitlist candidates using the United Network of Organ Sharing registry from May 2005 to 2020. After identifying an interaction between blood group and LAS, we evaluated the association between blood group and waitlist outcomes within LAS quartiles using unadjusted and adjusted competing risk models. RESULTS: In the lowest LAS quartile, blood group O had a 20% reduced transplantation rate (SHR: 0.80, 95%CI: 0.75-0.85) and higher waitlist death/removal (1.33, 95%CI: 1.15-1.55) compared with group A. Blood group AB had a 52% higher transplantation rate (SHR: 1.52, 95%CI: 1.34-1.73) in the lowest LAS quartile compared with group A. In the highest LAS quartile, there was no difference in transplantation rates between groups O and A. In contrast, group B had a 19% reduced transplantation rate (SHR, 0.81 95%CI: 0.73-0.89) and AB had a 28% reduced transplantation rate (SHR: 0.72, 95%CI: 0.61-0.86) in the highest LAS quartile. Additionally, groups B and AB had increased risk of waitlist death/removal in the highest LAS quartile compared with A (SHR: 1.27, 95%CI: 1.08-1.48; SHR: 1.31, 95%CI: 1.00-1.72). CONCLUSIONS: Waitlist outcomes among ABO blood groups vary depending on illness severity, which is represented by LAS. Blood group O has lower transplantation rates at low LAS while groups B and AB have lower transplantation rates at high LAS.


Assuntos
Sistema ABO de Grupos Sanguíneos , Pneumopatias , Transplante de Pulmão , Gravidade do Paciente , Obtenção de Tecidos e Órgãos , Listas de Espera , Humanos , Pulmão , Transplante de Pulmão/estatística & dados numéricos , Estudos Retrospectivos , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Sistema de Registros/estatística & dados numéricos , Estados Unidos/epidemiologia , Pneumopatias/epidemiologia , Pneumopatias/cirurgia
7.
Int Urol Nephrol ; 55(2): 295-300, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36171482

RESUMO

PURPOSE: Low-grade prostate cancer has low mortality rates at 10 years; however, it is unclear if the response is sustained for up to 25 years of follow-up. METHODS: Using Surveillance, Epidemiology, and End Results database, the overall and cancer-specific mortality rates were compared among men ≤ 55 years of age diagnosed with low-grade prostate cancer that either had radical prostatectomy, radiotherapy, or no known treatment. RESULTS: Of the 62,772 men diagnosed with low-grade prostate cancer between 1975 and 2016, about 60%, 20% and 20% of men underwent radical prostatectomy, radiotherapy, and no known treatment, respectively. At a median follow-up of 10 years, almost 2% and 7% of men died of prostate cancer and other causes, respectively. The overall mortality was significantly better in radical prostatectomy group compared to no known treatment group (HR 1.99, CI 1.84-2.15, P value < 0.001), but not between the radiotherapy and no known treatment groups. Moreover, the overall and cancer-specific mortality rates in the radiotherapy group were almost two and three times compared to the radical prostatectomy group, respectively (HR 2.15, CI 2.01-2.29, P value < 0.001 for overall mortality and HR 2.87, CI 2.5-3.29, P value < 0.001 for cancer-specific mortality). CONCLUSIONS: The study confirms low mortality rates in men diagnosed with low-grade prostate cancer for over 25 years' follow-up. While radical prostatectomy improves survival significantly compared to no known treatment, radiotherapy is associated with an increase in overall and cancer-specific mortality, which may be related to long-term toxicities.


Assuntos
Próstata , Neoplasias da Próstata , Masculino , Humanos , Adulto , Seguimentos , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/diagnóstico , Antígeno Prostático Específico , Prostatectomia/métodos
8.
Indian J Urol ; 38(3): 220-226, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35983120

RESUMO

Introduction: Studies directly comparing the different combination therapies offered to men with metastatic castration sensitive prostate cancer (mCSPC), are not available yet. This study was designed using the network meta-analysis (NMA) framework to provide a comparison of the different available options for the treatment of men with mCSPC. Methods: A systematic search was performed and the prospective randomized controlled trials reporting the overall survival (OS) or failure-free survival (FFS) were selected for review. A total of 14 studies were included in the NMA. Results: The addition of abiraterone, apalutamide, docetaxel, and docetaxel with zoledronic acid to the androgen deprivation therapy (ADT) demonstrated a significant improvement in the OS. In indirect comparison, abiraterone had a higher impact on the OS as compared to docetaxel (hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 1.0-1.46) and docetaxel with zoledronic acid (HR: 1.31, 95% CI: 1.05-1.63) but not apalutamide. Furthermore, apalutamide was not different than docetaxel or docetaxel with zoledronic acid. There was a significant improvement in the FFS with the combination of abiraterone, apalutamide, docetaxel (HR: 0.61, 95% CI: 0.46-0.81), docetaxel with zoledronic acid (HR: 0.62, 95% CI: 0.43-0.9), and enzalutamide (HR: 0.39, 95% CI: 0.25-0.61) as compared to the ADT alone. Similar to the indirect comparison of OS, abiraterone outperformed docetaxel (HR: 1.66, 95% CI: 1.12-2.47), docetaxel with zoledronic acid (HR: 1.69, 95% CI: 1.06-2.68), and enzalutamide (HR: 1.06, 95% CI: 0.63-1.80), but not apalutamide in terms of impact on the FFS. Conclusion: Overall, abiraterone demonstrated better OS and FFS outcomes as compared to all the other combination strategies in this NMA.

9.
Urology ; 168: 208-215, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35779711

RESUMO

OBJECTIVE: To assess whether estimated glomerular filtration rate (eGFR) independently predicts adverse outcomes after AUS surgery. METHODS: Using a large national database, we identified adult males who underwent AUS surgery between 2005-2019. To calculate eGFR (ml/min/1.73 m2), the Cockroft-Gault equation was utilized. Patients were classified into five different groups: 0-29 (advanced chronic kidney disease [CKD]), 30-59 (Stage III CKD), 60-89 (Stage II CKD), 90-119 (normal), and >120 (hyperfiltration). We investigated 30-day outcomes including any complication, readmission, reoperation, major and minor complications, extended length of stay, and non-home discharge. Multivariable logistic regression analysis (MLRA) was performed to assess eGFR categories as independent predictors for each outcome. RESULTS: A total of 1,910 cases met inclusion criteria. Patients with advanced CKD had a higher frailty burden (5-item modified frailty index ≥2: 39.1% vs. 22.2%), higher American Society of Anesthesiologists score (ASA III or IV: 95.7% vs. 53.5%), and lower BMI (median kg/m²: 29.3 vs. 30.9) compared to patients with normal eGFR. Likewise, patients with advanced CKD had higher rates of any complication, readmission, reoperation, extended length of stay, non-home discharge, as well as major and minor complications, compared to patients with normal eGFR. On MLRA, advanced CKD (0-29) was independently associated with reoperation (OR 5.14; 95% CI 1.06 - 20.84; p = 0.043). CONCLUSIONS: Patients with advanced CKD had a higher likelihood of reoperation when compared to patients with normal eGFR. Patients with advanced CKD should be counseled prior to AUS surgery due to a potential higher risk of 30-day reoperation.


Assuntos
Fragilidade , Insuficiência Renal Crônica , Esfíncter Urinário Artificial , Humanos , Adulto , Masculino , Taxa de Filtração Glomerular , Esfíncter Urinário Artificial/efeitos adversos , Fragilidade/complicações , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Reoperação
10.
Ann Thorac Surg ; 113(6): 1801-1810, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34280376

RESUMO

BACKGROUND: Gastroesophageal reflux disease (GERD) and aspiration of enteric contents are associated with worse outcomes after lung transplantation. The purpose of this study was to elucidate populations of patients who benefit the most from fundoplication after lung transplantation. METHODS: Lung transplantations from 2001 to 2019 (n = 971) were retrospectively reviewed and stratified by fundoplication before (n = 128) or after (n = 24) chronic lung allograft dysfunction (CLAD) development vs patients who did not undergo fundoplication. Patients with a fundoplication before CLAD were propensity matched to patients without a fundoplication. The primary outcome of interest was posttransplant survival. Time-to-event rates were calculated using a multivariable Cox proportional hazards model and Kaplan-Meier functions. RESULTS: Fundoplication before CLAD improved posttransplant survival before and after propensity matching, and it remained a significant predictor after adjusting for baseline characteristics (hazard ratio [HR],0.57; 95 % confidence interval [CI], 0.4 to 0.8; P = .001). Transplant recipients with a restrictive disorder (HR, 0.46; 95 % CI, 0.3 to 0.73; P = .001), age younger than 65 years (HR, 0.48; 95 % CI, 0.32 to 0.71; P < ;0.001), and with both single (HR, 0.47; 95 % CI, 0.28 to 0.79; P = .005) and double (HR, 0.55; 95 % CI, 0.32 to 0.93; P = .027) lung transplants had a significant decrease in mortality after fundoplication. The effect was present after excluding early deaths and CLAD diagnoses. Gastroesophageal reflux disease diagnosed by pH, impedance, or esophagogastroduodenoscopy was not associated with worse outcomes. Among patients with CLAD, a fundoplication was an independent predictor of post-CLAD survival (HR, 0.27; 95 % CI; 0.12 to 0.61; P = .002). CONCLUSIONS: Fundoplication before or after CLAD development is an independent predictor of survival. Younger patients with restrictive disease, independent of the type of transplant, have a survival benefit. Gastroesophageal reflux disease diagnosed by conventional methods was not associated with worse survival.


Assuntos
Refluxo Gastroesofágico , Transplante de Pulmão , Idoso , Fundoplicatura/métodos , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/cirurgia , Humanos , Pulmão , Transplante de Pulmão/métodos , Estudos Retrospectivos , Transplantados
11.
J Heart Lung Transplant ; 41(3): 382-390, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34949520

RESUMO

BACKGROUND: The primary lung allocation unit was expanded from the donation service area to a 250-mile radius in 2017. Prior to the change, geographic disparities in donor lung availability impacted waitlist outcomes. We sought to determine if the new allocation system improved these disparities. METHODS: We conducted a retrospective cohort study comparing the 2-year period before and after the change. Donor lung availability was defined as the ratio of donor lungs to waitlist candidates in the primary allocation unit. Transplant centers were divided into quartiles by donor lung availability. Multivariable competing risk models were used to determine the association between lung availability and waitlist outcomes. Multivariable Cox proportional hazards models compared post-transplant survival. RESULTS: Prior to the allocation change, the unadjusted transplant rate at centers in the lowest and highest quartiles was 132 and 607 transplants per 100 waitlist years. Candidates in the lowest quartile of donor lung availability had a 61% adjusted lower transplantation rate compared to candidates in highest quartile (sub-hazard ratio [sHR]: 0.39, 95% confidence interval [CI]: 0.34-0.44). After the allocation change, the disparity decreased resulting in an unadjusted transplant rate of 141 and 309 among centers in the lowest and highest quartiles. Candidates in the lowest quartile had a 38% adjusted lower transplantation rate compared to those in the highest (sHR: 0.62, 95% CI: 0.57-0.68). There was no significant difference in 1-year post-transplant survival. CONCLUSIONS: Although the expansion of the primary allocation unit improved disparities in waitlist outcomes without any change in post-transplant survival, there still remain significant differences due to geography.


Assuntos
Disparidades em Assistência à Saúde/estatística & dados numéricos , Transplante de Pulmão/estatística & dados numéricos , Obtenção de Tecidos e Órgãos/provisão & distribuição , Obtenção de Tecidos e Órgãos/normas , Idoso , Estudos de Coortes , Feminino , Geografia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Estados Unidos
12.
J Heart Lung Transplant ; 40(12): 1641-1648, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34548196

RESUMO

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is increasingly utilized as a bridge to lung transplantation, but ECMO status is not explicitly accounted for in the Lung Allocation Score (LAS). We hypothesized that among waitlist patients on ECMO, patients with pulmonary arterial hypertension (PAH) would have lower transplantation rates. METHODS: Using United Network for Organ Sharing data, we conducted a retrospective cohort study of patients who were ≥12 years old, active on the lung transplant waitlist, and required ECMO support from June 1, 2015 through June 12, 2020. Multivariable competing risk analysis was used to examine waitlist outcomes. RESULTS: 1064 waitlist subjects required ECMO support; 40 (3.8%) had obstructive lung disease (OLD), 97 (9.1%) had PAH,138 (13.0%) had cystic fibrosis (CF), and 789 (74.1%) had interstitial lung disease (ILD). Ultimately, 671 (63.1%) underwent transplant, while 334 (31.4%) died or were delisted. The transplant rate per person-years on the waitlist on ECMO was 15.41 for OLD, 6.05 for PAH, 15.66 for CF, and 15.62 for ILD. Compared to PAH patients, OLD, CF, and ILD patients were 78%, 69%, and 62% more likely to undergo transplant throughout the study period, respectively (adjusted SHRs 1.78 p = 0.007, 1.69 p = 0.002, and 1.62 p = 0.001). The median LAS at waitlist removal for transplantation, death, or delisting were 75.1 for OLD, 79.6 for PAH, 91.0 for CF, and 88.3 for ILD (p < 0.001). CONCLUSIONS: Among patients bridging to transplant on ECMO, patients with PAH had a lower transplantation rate than patients with OLD, CF, and ILD.


Assuntos
Fibrose Cística/cirurgia , Oxigenação por Membrana Extracorpórea , Disparidades em Assistência à Saúde/estatística & dados numéricos , Doenças Pulmonares Intersticiais/cirurgia , Transplante de Pulmão/estatística & dados numéricos , Hipertensão Arterial Pulmonar/cirurgia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Estudos Retrospectivos , Obtenção de Tecidos e Órgãos , Listas de Espera
13.
J Heart Lung Transplant ; 40(9): 998-1008, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34183226

RESUMO

INTRODUCTION: Duodeno-gastroesophageal reflux aspiration is associated with chronic lung allograft dysfunction (CLAD). Reflux aspirate can contain bile acids (BA), functional molecules in the gastro-intestinal tract with emulsifying properties. We sought to determine and quantify the various BA species in airways of the lung transplant recipients to better understand the various effects of aspirated BA that contribute to post-transplantation outcomes. METHODS: Bronchial washings (BW) were prospectively collected from lung transplant recipients and subsequently assayed by liquid chromatography-mass spectrometry for 13 BA and 25 lipid families. Patients were monitored for CLAD, rejection, inflammation and airway infections. RESULTS: Detectable BA were present in 45/50 patients (90%) at 3 months after transplant. Elevated BA and predominance of conjugated species were independent predictors of CLAD (hazard ratio 7.9; 95% confidence interval 2.7-23.6; p < 0.001 and 7.3; 2.4-22; p < 0.001, respectively) and mortality (hazard ratio 4.4; 1.5-12.7; p = 0.007 and 4.8; 1.4-15.8; p = 0.01, respectively). High BA associated with increased positive bacterial cultures (60% vs 25%, p = 0.02). Primary conjugated species independently correlated with the rate of bacterial cultures during the first-year post-transplant (Beta coefficient: 0.77; 0.28-1.26; p = 0.003) and changes in airway lipidome and cytokines. CONCLUSIONS: Higher BA levels and predominance of conjugated BA are independent predictors of chronic lung allograft dysfunction, mortality and bacterial infections. Primary conjugated BA are related to distinct changes in airway lipidome and inflammatory cytokines. This elucidates novel evidence into the mechanism following BA aspiration and proposes novel markers for prediction of adverse post-transplant outcomes.


Assuntos
Ácidos e Sais Biliares/análise , Líquido da Lavagem Broncoalveolar/química , Citocinas/análise , Lipídeos/análise , Transplante de Pulmão/efeitos adversos , Pulmão/metabolismo , Adulto , Biomarcadores/análise , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
14.
Transplantation ; 105(4): 861-866, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33760792

RESUMO

BACKGROUND: Regional variation in lung transplantation practices due to local coronavirus disease 2019 (COVID-19) prevalence may cause geographic disparities in access to lung transplantation. METHODS: Using the United Network for Organ Sharing registry, we conducted a descriptive analysis of lung transplant volume, donor lung volume, new waitlist activations, and waiting list deaths at high-volume lung transplant centers during the first 3 months of the pandemic (March 1. 2020, to May 30, 2020) and we compared it to the same period in the preceding 5 years. RESULTS: Lung transplant volume decreased by 10% nationally and by a median of 50% in high COVID-19 prevalence centers (range -87% to 80%) compared with a median increase of 10% (range -87% to 80%) in low prevalence centers (P-for-trend 0.006). Donation services areas with high COVID-19 prevalence experienced a greater decrease in organ availability (-28% range, -72% to -11%) compared with low prevalence areas (+7%, range -20% to + 55%, P-for-trend 0.001). Waiting list activations decreased at 18 of 22 centers. Waiting list deaths were similar to the preceding 5 years and independent of local COVID-19 prevalence (P-for-trend 0.36). CONCLUSIONS: Regional variation in transplantation and donor availability in the early months of the pandemic varied by local COVID-19 activity.


Assuntos
COVID-19/epidemiologia , Transplante de Pulmão , Pandemias , SARS-CoV-2 , Obtenção de Tecidos e Órgãos , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Transplante de Pulmão/estatística & dados numéricos , Transplante de Pulmão/tendências , Masculino , Pessoa de Meia-Idade , Prevalência , Sistema de Registros/estatística & dados numéricos , Estudos Retrospectivos , Doadores de Tecidos/estatística & dados numéricos , Doadores de Tecidos/provisão & distribuição , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Obtenção de Tecidos e Órgãos/tendências , Estados Unidos/epidemiologia , Listas de Espera/mortalidade , Adulto Jovem
15.
Sci Data ; 8(1): 76, 2021 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-33674581

RESUMO

The Buzzards Bay Coalition's Baywatchers Monitoring Program (Baywatchers) collected summertime water quality information at more than 150 stations around Buzzards Bay, Massachusetts from 1992 to 2018. Baywatchers documents nutrient-related water quality and the effects of nitrogen pollution. The large majority of stations are located in sub-estuaries of the main Bay, although stations in central Buzzards Bay and Vineyard Sound were added beginning in 2007. Measurements include temperature, salinity, Secchi depth and concentrations of dissolved oxygen, ammonium, nitrate + nitrite, total dissolved nitrogen, particulate organic nitrogen, particulate organic carbon, ortho-phosphate, chlorophyll a, pheophytin a, and in lower salinity waters, total phosphorus and dissolved organic carbon. The Baywatchers dataset provides a long-term record of the water quality of Buzzards Bay and its sub-estuaries. The data have been used to identify impaired waters, evaluate discharge permits, support the development of nitrogen total maximum daily loads, develop strategies for reducing nitrogen inputs, and increase public awareness and generate support for management actions to control nutrient pollution and improve water quality.

16.
J Scleroderma Relat Disord ; 6(3): 247-255, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35387211

RESUMO

Introduction: Gastroesophageal reflux and aspiration are risk factors for chronic lung allograft dysfunction in lung transplant recipients. Patients with systemic sclerosis are at an increased risk of aspiration due to esophageal dysmotility and an ineffective lower esophageal sphincter. The aim of this study is to understand the effect of fundoplication on outcomes in systemic sclerosis recipients. Methods: Between 2001 and 2019, 168 systemic sclerosis patients were referred for lung transplantation-51 (30.3%) were listed and 36 (21.4%) were transplanted. Recipients were stratified whether they underwent a fundoplication (n = 10, 27.8%) or not (n = 26, 72.2%). Freedom from chronic lung allograft dysfunction and survival were analyzed using log-rank test. Multivariable analysis for known risk factors was performed using a Cox-proportional hazards model. Results: Median time to fundoplication after transplantation was 16.4 months (interquartile range: 9.6-25.1) and all were laparoscopic (Dor 50%, Nissen 40%, Toupet 10%). There were no differences in acute rejection ⩾ A1 (26.9% vs 30%), or primary graft dysfunction grades 2-3 at 72 h (42.3% vs 40%) between groups. Recipients with fundoplication had an increased freedom from chronic lung allograft dysfunction (p = 0.035) and overall survival (p = 0.01). Fundoplication was associated with a reduced risk of mortality adjusting for other comorbidities (hazard ratio = 0.13; 95% confidence interval = 0.02-0.65; p = 0.014). Double and single lung transplant did not have different post-transplant survival. Conclusion: Fundoplication in systemic sclerosis lung transplant recipients is associated with greater freedom from chronic lung allograft dysfunction and overall survival. Screening for reflux and aspiration followed by early fundoplication may delay graft deterioration in this population.

17.
J Endourol ; 35(4): 409-416, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32962442

RESUMO

Objective: This study was designed to provide an indirect comparison of the urinary and sexual domain outcomes and complications after newer minimally invasive surgical therapy (MIST) of Aquablation, Rezum, and UroLift for benign prostatic hyperplasia (BPH) for transurethral resection of prostate (TURP). Methods: We searched Embase, Medline, and Cochrane in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, in December 2019. Only randomized clinical trials (RCTs) that reported outcomes after treatment of BPH for prostate less than 80 g with Aquablation, Rezum, or UroLift were included in the analysis. Results: A total of four RCTs reporting the outcomes after treatment with newer MIST for BPH were identified. Patients undergoing the resective procedures, that is, TURP and Aquablation, had greater improvement in urinary domain outcomes: International Prostate Symptom Score, quality of life, peak flow rate, and postvoiding residual compared to patients undergoing nonresective procedures: UroLift and Rezum. Patients in UroLift group maintained a higher sexual function domain score compared to TURP, but not Aquablation. Our multiple comparison analysis did not reveal a significant difference in urinary and sexual domain scores between patients undergoing UroLift and Rezum at 24 months of follow-up. Conclusions: Aquablation and TURP necessitate general or regional anesthesia and both produced significantly better urinary domain scores compared to Rezum and UroLift. On the other hand, UroLift demonstrated better sexual function domain scores compared to TURP, but not Aquablation. There was no significant difference in urinary domain scores between UroLift and Rezum at 24 months of follow-up.


Assuntos
Sintomas do Trato Urinário Inferior , Hiperplasia Prostática , Ressecção Transuretral da Próstata , Humanos , Sintomas do Trato Urinário Inferior/cirurgia , Masculino , Procedimentos Cirúrgicos Minimamente Invasivos , Metanálise em Rede , Hiperplasia Prostática/cirurgia , Resultado do Tratamento
18.
Urol Oncol ; 39(8): 493.e1-493.e7, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33353870

RESUMO

BACKGROUND: Recent guidelines recommend active management of prostate cancer (CaP), especially high-risk disease, in elderly men. However, descriptive data from a large cohort with extended follow up on the risk of death from CaP in men diagnosed over 70 years of age and its relationship to Gleason score (GS) and serum prostate specific antigen (PSA) level is lacking. Using the Surveillance, Epidemiology, and End Results database, we evaluated the influence of GS and serum PSA levels on the risks of mortality from PC (PCM) and mortality from other causes in localized (LPC) and metastatic (MPC) disease in elderly population. METHODS: Men diagnosed with PC over 70 years of age between 2004 and 2016 were divided into LPC and MPC groups, categorized by age: 70-74, 75-79, 80-84, 85-89, and ≥90 years and stratified by GS <7, 7, and >7, and serum PSA level <4, 4-10, 10-20, 20-50, and >50 ng/mL. Competing risk estimates for PCM and mortality from other causes were generated for both groups. RESULTS: Of the 85,649 men, 85.5 % were LPC at diagnosis. Overall, at a median follow up of 4 years, 15% of the men had died including a third from PC. While <15% of men with GS ≤7 died from PC, the PCM was >30% in men with GS >7 in LPC group, which accounted for almost half of total deaths for age 70-84 years. The GS >7 was also significantly associated with PCM in men with MPC. Furthermore, PCM directly correlated with serum PSA levels, with mortality rates reaching up to 50% and 70% for PSA >50 ng/dl for LPC and MPC, respectively. CONCLUSIONS: There is a substantial risk of dying in men diagnosed with LPC over 70 years of age with GS >7 or a serum PSA >20 ng/mL. Furthermore, the risk for death for MPC directly correlated with GS with PCM increasing from 10%-30% for GS ≤7 to >50% for GS >7. The data, in conjunction with other clinical parameters such as comorbidities could be used to counsel elderly men on management options of PC for both localized and metastatic PC.


Assuntos
Prostatectomia/mortalidade , Neoplasias da Próstata/mortalidade , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Seguimentos , Humanos , Masculino , Gradação de Tumores , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Taxa de Sobrevida
19.
J Robot Surg ; 15(3): 321-333, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33222043

RESUMO

Over the last decade, the increased utilization of robot-assisted radical cystectomy (RARC) in the surgical treatment of muscle-invasive bladder cancer has led to an uptrend in intracorporeal urinary diversions (ICUD). However, the operative results comparing ICUD to extracorporeal urinary diversion (ECUD) have varied widely. We performed a meta-analysis to analyze perioperative outcomes and complications of ICUD compared to ECUD following RARC. This study is registered at International Prospective Register of Systematic Reviews (PROSPERO) CRD42020164074. A systematic literature review was conducted using PubMed, EMBASE, and Cochrane databases in August 2019. A total of six studies comparing ICUD vs ECUD were identified and meta-analysis was conducted on these studies. In addition, a cumulative analysis was also performed on 83 studies that reported perioperative outcomes after RARC and ICUD or ECUD. The Weighed Mean Difference of operative time and blood loss between ICUD and ECUD group was (16; 95% confidence interval - 34 to 66) and (- 86; 95% confidence interval - 124 to - 48), respectively. ICUD and ECUD had comparable early (30-day) and mid-term (30-90-day) complication rate (RR 1.19; 95% confidence interval 0.71-2.0; p = 0.5) and (RR 0.91; 95% confidence interval 0.71-1.15 p = 0.4) respectively. In the 83 studies that were included in the cumulative analysis, the mean operative time for ileal conduit and neobladders by ICUD were 307 and 428 min, respectively, compared to ECUD 428 and 426 min, respectively. ICUD and ECUD have comparable short- and mid-term complication rate. The ICUD group has lower blood loss and lower rate of blood transfusion compared to ECUD.


Assuntos
Cistectomia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias da Bexiga Urinária/cirurgia , Derivação Urinária/métodos , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Transfusão de Sangue/estatística & dados numéricos , Feminino , Humanos , Masculino , Invasividade Neoplásica , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento , Neoplasias da Bexiga Urinária/patologia , Derivação Urinária/efeitos adversos
20.
Ann Transplant ; 25: e922641, 2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32807766

RESUMO

BACKGROUND Morbidity and mortality rates after lung transplantation remain high compared to other solid organ transplants. In the lung allocation score era, patients given the highest priority on the waitlist are those with the greatest severity of illness, who often require preoperative hospitalization. MATERIAL AND METHODS To determine the association of pre-transplant hospitalization with post-transplant outcomes, we retrospectively evaluated 448 lung transplant recipients at our center between January 2010 and July 2017 (114 hospitalized; 334 outpatient). RESULTS Survival was similar between the groups (hazard ratio 0.93 [95% CI 0.61 to 1.42], p=0.738). However, hospitalized patients had longer hospital and intensive care unit length of stay compared to outpatients - 25 vs. 18 days, (p<0.001) and 9.5 vs. 6 days, (p<0.001), respectively. Hospitalized patients had higher rates of Grade 3 primary graft dysfunction - 29.8% vs. 9.6%, p<0.001 - and remained mechanically ventilated longer - 6 vs. 3 days, p<0.001. A greater percentage of hospitalized patients needed a tracheostomy and a re-operation within 30 days - 39.5% vs. 15.3% (p<0.001) and 22.8% vs. 12.0% (p=0.005) - respectively. After discharge, 28% of hospitalized patients required acute rehabilitation compared with 12% of outpatients (p=0.001). CONCLUSIONS While pre-transplant hospitalization is not associated with mortality, it is associated with significant morbidity after transplant.


Assuntos
Pneumopatias/cirurgia , Transplante de Pulmão/efeitos adversos , Transplante de Pulmão/mortalidade , Transplantados , Adulto , Idoso , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados da Assistência ao Paciente , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Listas de Espera
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