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BACKGROUND: Cerebrospinal fluid creatine kinase BB isoenzyme (CSF CK-BB) after cardiac arrest (CA) has been shown to have a high positive predictive value for poor neurological outcome, but it has not been evaluated in the setting of targeted temperature management (TTM) and modern CA care. We aimed to evaluate CSF CK-BB as a prognostic biomarker after CA. METHODS: We performed a retrospective cohort study of patients with CA admitted between 2010 and 2020 to a three-hospital health system who remained comatose and had CSF CK-BB assayed between 36 and 84 h after CA. We examined the proportion of patients at hospital discharge who achieved favorable or intermediate neurological outcome, defined as Cerebral Performance Category score of 1-3, compared with those with poor outcome (Cerebral Performance Category score 4-5) for various CSF CK-BB thresholds. We also evaluated additive value of bilateral absence of somatosensory evoked potentials (SSEPs). RESULTS: Among 214 eligible patients, the mean age was 54.7 ± 4.8 years, 72% of patients were male, 33% were nonwhite, 17% had shockable rhythm, 90% were out-of-hospital CA, and 83% received TTM. A total of 19 (9%) awakened. CSF CK-BB ≥ 230 U/L predicted a poor outcome at hospital discharge, with a specificity of 100% (95% confidence interval [CI] 82-100%) and sensitivity of 69% (95% CI 62-76%). When combined with bilaterally absent N20 response on SSEP, specificity remained 100% while sensitivity increased to 80% (95% CI 73-85%). Discordant CK-BB and SSEP findings were seen in 13 (9%) patients. CONCLUSIONS: Cerebrospinal fluid creatine kinase BB isoenzyme levels accurately predicted poor neurological outcome among CA survivors treated with TTM. The CSF CK-BB cutoff of 230 U/L optimizes sensitivity to 69% while maintaining a specificity of 100%. CSF CK-BB could be a useful addition to multimodal neurological prognostication after CA.
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BACKGROUND: Bladder cancer poses a significant public health burden, with high recurrence and progression rates in patients with non-muscle-invasive bladder cancer (NMIBC). Current treatment options include bladder-sparing therapies (BST) and radical cystectomy, both with associated risks and benefits. However, evidence supporting optimal management decisions for patients with recurrent high-grade NMIBC remains limited, leading to uncertainty for patients and clinicians. The CISTO (Comparison of Intravesical Therapy and Surgery as Treatment Options) Study aims to address this critical knowledge gap by comparing outcomes between patients undergoing BST and radical cystectomy. METHODS: The CISTO Study is a pragmatic, prospective observational cohort trial across 36 academic and community urology practices in the US. The study will enroll 572 patients with a diagnosis of recurrent high-grade NMIBC who select management with either BST or radical cystectomy. The primary outcome is health-related quality of life (QOL) at 12 months as measured with the EORTC-QLQ-C30. Secondary outcomes include bladder cancer-specific QOL, progression-free survival, cancer-specific survival, and financial toxicity. The study will also assess patient preferences for treatment outcomes. Statistical analyses will employ targeted maximum likelihood estimation (TMLE) to address treatment selection bias and confounding by indication. DISCUSSION: The CISTO Study is powered to detect clinically important differences in QOL and cancer-specific survival between the two treatment approaches. By including a diverse patient population, the study also aims to assess outcomes across the following patient characteristics: age, gender, race, burden of comorbid health conditions, cancer severity, caregiver status, social determinants of health, and rurality. Treatment outcomes may also vary by patient preferences, health literacy, and baseline QOL. The CISTO Study will fill a crucial evidence gap in the management of recurrent high-grade NMIBC, providing evidence-based guidance for patients and clinicians in choosing between BST and radical cystectomy. The CISTO study will provide an evidence-based approach to identifying the right treatment for the right patient at the right time in the challenging clinical setting of recurrent high-grade NMIBC. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03933826. Registered on May 1, 2019.
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Neoplasias Vesicales sin Invasión Muscular , Neoplasias de la Vejiga Urinaria , Humanos , Adyuvantes Inmunológicos/uso terapéutico , Administración Intravesical , Vacuna BCG/uso terapéutico , Cistectomía , Estudios Multicéntricos como Asunto , Invasividad Neoplásica , Recurrencia Local de Neoplasia/tratamiento farmacológico , Estudios Observacionales como Asunto , Estudios Prospectivos , Calidad de Vida , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/cirugía , Ensayos Clínicos Pragmáticos como AsuntoRESUMEN
PURPOSE: We developed prediction models for postoperative respiratory depression and respiratory complications for 958 patients who were on methadone preoperatively. METHODS: The primary outcome was postoperative respiratory depression as defined by respiratory rate < 10/min, oxygen saturation (SpO2) < 90%, or requirement of naloxone for 48 h postoperatively. Secondary outcome was the composite of postoperative respiratory complications. Prediction models for postoperative respiratory depression and respiratory complications were constructed using multivariate logistic regression with preoperative and intraoperative characteristics as the predictors. RESULTS: For the multivariate logistic regression model for postoperative respiratory depression, surgery duration (P = 0.005), body mass index (BMI) (P = 0.008), surgery involving digestive system (P = 0.031), and American Society of Anesthesiologists (ASA) physical status ≥ 4 (P = 0.038) were statistically significant predictors. The area under the receiver operating characteristic curve (AUROC) of the model was 0.581 (0.558-0.601) [median (95% confidence interval (CI))] with fivefold cross-validation. For the model for postoperative respiratory complications, surgery duration (P = 0.001), history of hypertension (P = 0.028), surgery involving musculoskeletal system (P < 0.001), surgery involving integumental system (P = 0.034), surgery categorized to miscellaneous therapeutic procedures (P = 0.028), combined general and regional anesthesia (P = 0.033), ASA physical status 3 (P < 0.001), and ASA physical status ≥ 4 (P < 0.001) were statistically significant predictors, and AUROC of the model was 0.726 (0.712-0.737). CONCLUSIONS: Multivariate logistic regression models including preoperative, and intraoperative characteristics as the predictors performed poorly to predict postoperative respiratory depression, and moderately for postoperative respiratory complications. Neither model is accurate enough to be subject to clinical use.
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Trastornos Respiratorios , Insuficiencia Respiratoria , Humanos , Metadona , Frecuencia Respiratoria , Complicaciones Posoperatorias/etiología , Factores de Riesgo , Estudios RetrospectivosRESUMEN
Importance: Acute cholecystitis (AC) management during pregnancy requires balancing the risk of pregnancy loss or preterm delivery (adverse pregnancy outcomes [APOs]) with or without surgery. Guidelines recommend cholecystectomy across trimesters; however, trimester-specific evidence on the risks of AC and its management is lacking. Objective: To assess cholecystectomy frequency in pregnant people with AC, compare the rates of APOs in pregnant people with or without AC, and compare the rates of APOs in people with AC who did or did not undergo cholecystectomy. Design, Setting, and Participants: This retrospective, population-based cohort study used data for pregnant people with AC from the IBM MarketScan Commercial Claims and Encounters Database from January 1, 2007, to December 31, 2019, and a propensity score-matched cohort of pregnant people without AC. Trimester status (first [T1], second [T2], and third [T3]), APOs, and cholecystectomy were defined by administrative claims. Data were analyzed from October 2021 to July 2022. Exposures: Pregnant patients with or without AC. Pregnant patients with AC who did or did not receive cholecystectomy. Main Outcomes and Measures: The main outcomes were cholecystectomy during pregnancy and APOs (ie, preterm delivery and pregnancy loss). Pregnant patients with and without AC were compared to assess the association of AC with risk of APOs. Propensity score inverse-probability weighting was used to calculate treatment-associated APO risk among patients with 1-year follow-up. Results: The study included 5759 pregnant patients with AC (mean [SD] age, 30.1 [6.6] years) and 23â¯036 controls (mean [SD] age, 29.9 [6.7] years) after propensity score matching. Among 3426 pregnant patients with AC and 1-year follow-up, 1182 (34.5%) underwent cholecystectomy during the pregnancy (684 [41.7%] presenting with AC in T1, 404 [40.4%] in T2, and 94 [12.0%] in T3). Acute cholecystitis during pregnancy, irrespective of treatment, was associated with higher odds of APO compared with no AC during pregnancy across all trimesters (odds ratio [OR], 1.69 [95% CI, 1.54-1.85]). Compared with nonoperative management, receipt of surgery was associated with lower odds of APOs across all trimesters (OR, 0.75 [95% CI, 0.63-0.87]), in T1 (OR, 0.81 [95% CI, 0.66-1.00]), in T2 (OR, 0.71 [95% CI, 0.50-1.00]), and in T3 (OR, 0.45 [95% CI, 0.28-0.70]). Conclusions and Relevance: In this study, cholecystectomy was associated with lower risk of APO in patients with AC across all trimesters, with the greatest benefit in T3. However, only 34.5% overall and 12.0% of patients in T3 had a cholecystectomy. These findings support guidelines recommending cholecystectomy during pregnancy and should inform decision-making discussions. Greater guideline adherence and surgery use, especially in T3, may represent an opportunity to improve outcomes for pregnant people with AC.
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Colecistitis Aguda , Nacimiento Prematuro , Embarazo , Femenino , Recién Nacido , Humanos , Adulto , Estudios de Cohortes , Estudios Retrospectivos , Resultado del Embarazo , Colecistitis Aguda/cirugíaRESUMEN
Previous studies demonstrate that self-reports of mammography screening for breast cancer and colonoscopy screening for colorectal cancer demonstrate concordance, based on adherence to screening guidelines, with electronic medical records (EMRs) in over 90% of those interviewed, as well as high sensitivity and specificity, and can be used for monitoring our Healthy People goals. However, for screening tests for cervical and lung cancers, and for various sub-populations, concordance between self-report and EMRs has been noticeably lower with poor sensitivity or specificity. This study aims to test the validity and reliability of lung, colorectal, cervical, and breast cancer screening questions from the 2021 and 2022 National Health Interview Survey (NHIS). We present the protocol for a study designed to measure the validity and reliability of the NHIS cancer screening questions compared to EMRs from four US-based healthcare systems. We planned a randomized trial of a phone- vs web-based survey with NHIS questions that were previously revised based on extensive cognitive interviewing. Our planned sample size will be 1576 validity interviews, and 1260 interviews randomly assigned at 1 or 3 months after the initial interview. We are enrolling people eligible for cancer screening based on age, sex, and smoking history per US Preventive Services Task Force recommendations. We will evaluate question validity using concordance, sensitivity, specificity, positive predictive value, negative predictive value, and report-to-records ratio. We further are randomizing participants to complete a second survey 1 vs 3 months later to assess question reliability. We suggest that typical measures of concordance may need to be reconsidered in evaluating cancer screening questions.
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Neoplasias de la Mama , Neoplasias Colorrectales , Neoplasias Pulmonares , Humanos , Femenino , Detección Precoz del Cáncer , Neoplasias Pulmonares/diagnóstico por imagen , Reproducibilidad de los Resultados , Cuello , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias Colorrectales/diagnósticoRESUMEN
ABSTRACT: Up to a third of patients with hemato-oncologic conditions who have received multiply transfusions develop immune-mediated platelet transfusion refractoriness. Yet factors that influence posttransfusion platelet corrected count increments (CCI) in patients with HLA-alloimmune platelet transfusion refractoriness remain less well elucidated. Recent advances in HLA antibody characterization using fluorescent bead-based platforms enable the study of donor-specific antibody (DSA) avidity (as measured by mean fluorescence intensity [MFI]) and its impact on HLA-alloimmune platelet transfusion refractoriness. In this large retrospective study of 2012 platelet transfusions among 73 HLA-alloimmunized patients, we evaluated the impact of cumulative HLA DSA-MFI alongside other donor, platelet component, and patient characteristics on CCI at 2 and 24 hours after transfusion. As part of a quality improvement initiative, we also developed and tested a computerized algorithm to optimize donor-recipient histocompatibility based on cumulative DSA-MFI and sought other actionable predictors of CCI. In multivariate analyses, cumulative HLA DSA-MFI of ≥10 000, major/bidirectional ABO-mismatch, splenomegaly, transfusion reactions, and platelet storage in additive solution negatively affected 2-hour but not 24-hour posttransfusion CCI. The DSA-MFI threshold of 10 000 was corroborated by greater antibody-mediated complement activation and significantly more CCI failures above this threshold, suggesting the usefulness of this value to inform "permissive platelet mismatching" and to optimize CCI. Furthermore, DSA-MFI decreases were deemed feasible by the computer-based algorithm for HLA-platelet selection in a pilot cohort of 8 patients (122 transfusions) evaluated before and after algorithm implementation. When HLA-selected platelets are unavailable, ABO-identical/minor-mismatched platelet concentrates may enhance 2-hour CCI in heavily HLA-alloimmunized patients with platelet transfusion refractoriness.
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Antígenos HLA , Isoanticuerpos , Transfusión de Plaquetas , Humanos , Transfusión de Plaquetas/efectos adversos , Antígenos HLA/inmunología , Isoanticuerpos/inmunología , Isoanticuerpos/sangre , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Adulto , Anciano , Donantes de Sangre , Plaquetas/inmunologíaRESUMEN
OBJECTIVE: Defining a clinician's ability to perceptually identify mass from voice will inform the feasibility, design priorities, and performance standards for tools developed to screen for laryngeal mass from voice. This study defined clinician ability of and examined the impact of expertise on screening for laryngeal mass from voice. STUDY DESIGN: Task comparison study between experts and nonexperts rating voices for the probability of a laryngeal mass. SETTING: Online, remote. METHODS: Experts (voice-focused speech-language pathologists and otolaryngologists) and nonexperts (general medicine providers) rated 5-s/i/voice samples (with pathology defined by laryngoscopy) for the probability of laryngeal mass via an online survey. The intraclass correlation coefficient (ICC) estimated interrater and intrarater reliability. Diagnostic performance metrics were calculated. A linear mixed effects model examined the impact of expertise and pathology on ratings. RESULTS: Forty clinicians (21 experts and 19 nonexperts) evaluated 344 voice samples. Experts outperformed nonexperts, with a higher area under the curve (70% vs 61%), sensitivity (49% vs 36%), and specificity (83% vs 77%) (all comparisons p < .05). Interrater reliability was fair for experts and poor for nonexperts (ICC: 0.48 vs 0.34), while intrarater reliability was excellent and good, respectively (ICC: 0.9 and 0.6). The main effects of expertise and underlying pathology were significant in the linear model (p < .001). CONCLUSION: Clinicians demonstrate inadequate performance screening for laryngeal mass from voice to use auditory perception for dysphonia triage. Experts' superior performance indicates that there is acoustic information in a voice that may be utilized to detect laryngeal mass based on voice.
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Disfonía , Voz , Humanos , Reproducibilidad de los Resultados , Calidad de la Voz , Disfonía/diagnóstico , Percepción AuditivaRESUMEN
We have shown that activin A (activin), a TGF-ß superfamily member, has pro-metastatic effects in colorectal cancer (CRC). In lung cancer, activin activates pro-metastatic pathways to enhance tumor cell survival and migration while augmenting CD4+ to CD8+ communications to promote cytotoxicity. Here, we hypothesized that activin exerts cell-specific effects in the tumor microenvironment (TME) of CRC to promote anti-tumoral activity of immune cells and the pro-metastatic behavior of tumor cells in a cell-specific and context-dependent manner. We generated an Smad4 epithelial cell specific knockout (Smad4-/-) which was crossed with TS4-Cre mice to identify SMAD-specific changes in CRC. We also performed IHC and digital spatial profiling (DSP) of tissue microarrays (TMAs) obtained from 1055 stage II and III CRC patients in the QUASAR 2 clinical trial. We transfected the CRC cells to reduce their activin production and injected them into mice with intermittent tumor measurements to determine how cancer-derived activin alters tumor growth in vivo. In vivo, Smad4-/- mice displayed elevated colonic activin and pAKT expression and increased mortality. IHC analysis of the TMA samples revealed increased activin was required for TGF-ß-associated improved outcomes in CRC. DSP analysis identified that activin co-localization in the stroma was coupled with increases in T-cell exhaustion markers, activation markers of antigen presenting cells (APCs), and effectors of the PI3K/AKT pathway. Activin-stimulated PI3K-dependent CRC transwell migration, and the in vivo loss of activin lead to smaller CRC tumors. Taken together, activin is a targetable, highly context-dependent molecule with effects on CRC growth, migration, and TME immune plasticity.
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INTRODUCTION: Preexisting chronic pain has been reported to be a consistent risk factor for severe acute postoperative pain. However, each specific chronic pain condition has unique pathophysiology, and it is possible that the effect of each condition on postoperative pain is different. METHODS: This is a retrospective cohort study of pregnant women with preexisting chronic pain conditions (i.e., migraine, chronic back pain, and the combination of migraine + chronic back pain), who underwent cesarean delivery. The effects of the three chronic pain conditions on time-weighted average (TWA) pain score (primary outcome) and opioid dose requirements in morphine milligram equivalents (MME) during postoperative 48 hours were compared. RESULTS: The TWA pain score was similar in preexisting migraine and chronic back pain. Chronic back pain was associated with significantly greater opioid dose requirements than migraine (12.92 MME, 95% CI: 0.41 to 25.43, P=0.041). Preoperative opioid use (P < 0.001) was associated with a greater TWA pain score. Preoperative opioid use (P < 0.001), smoking (P=0.004), and lower postoperative ibuprofen dose (P=0.002) were associated with greater opioid dose requirements. CONCLUSIONS: Findings suggest women with chronic back pain and migraine do not report different postpartum pain intensities; however, women with preexisting chronic back pain required 13 MME greater opioid dose than those with migraine during 48 hours after cesarean delivery.