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1.
Article in English | MEDLINE | ID: mdl-38950771

ABSTRACT

OBJECTIVE: Research into the risk factors associated with late recurrence (>2 years after surgery) of lung adenocarcinoma (LUAD) is limited. We investigated the incidence of and clinicopathologic and genomic features associated with late recurrence of resected stage I-IIIA LUAD. METHODS: We performed a retrospective analysis of patients with completely resected pathologic stage I-IIIA LUAD (2010-2019). Patients with a history of lung cancer, neoadjuvant therapy, or mucinous or noninvasive LUAD, or with follow-up of <2 years were excluded. Cox and logistic regression modeling were used to compare clinicopathologic variables among patients with no, early (≤2 years), and late recurrence. Comparisons of genomic mutations were corrected for multiple testing. RESULTS: Of the 2349 patients included, 537 developed a recurrence during follow-up. Most recurrences (55% [297/537]) occurred early; 45% (240/537) occurred late. A larger proportion of late recurrences than early recurrences were locoregional (37% vs. 29%; p=0.047). Patients with late recurrence had more aggressive pathologic features (IASLC grade 2 and 3, lymphovascular invasion, visceral pleural invasion) and higher stage than patients without recurrence. Pathologic features were similar between patients with early and late recurrence, except stage IIIA disease was more common in the early cohort. No genomic mutations were associated with late recurrence. CONCLUSIONS: Late recurrence of LUAD following resection is more common than previously reported. Patients without disease >2 years after surgery who had aggressive pathologic features at the time of resection have an elevated risk of recurrence and may benefit from more-aggressive follow-up.

2.
Ann Thorac Surg ; 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38866198

ABSTRACT

BACKGROUND: Results of recent clinical trials suggest that segmentectomy may be an acceptable alternative to lobectomy for selected patients with early-stage non-small cell lung cancer (NSCLC). Increased use of segmentectomy may result in a concomitant increase in occult node-positive (N+) disease on surgical pathology examination. The optimal management for such patients remains unknown. METHODS: Clinicopathologic data were abstracted from a prospective institutional database to identify patients with pathologic N+ disease after segmentectomy for cT1 N0 M0 NSCLC. Propensity score matching identified a comparable lobectomy cohort for assessment of cumulative incidence of recurrence and overall survival (OS). RESULTS: Of 759 included patients, 27 (4%) had nodal upstaging on the final pathology report. Of these 27 patients, 4 (15%) had skip metastasis to N2 stations, and 20 (74%) received adjuvant therapy; no completion lobectomies were performed. Ten patients (37%) had disease recurrence: 3 isolated locoregional (11%) and 7 distant (26%). The median time to recurrence among patients with recurrence was 1.8 years; OS after recurrence was 3.4 years. After 5:1 matching with 109 patients who underwent lobectomy, all variables were balanced between the groups, except pathologic N2 stage and open surgical approach. The 5-year cumulative incidence of recurrence was not significantly different between segmentectomy and lobectomy (42% vs 52%, respectively; Gray's P = .1). The 5-year OS (63% and 50%) and rate of locoregional recurrence (12% vs 13%) were not statistically different between the groups. CONCLUSIONS: Patients with occult N+ disease after segmentectomy for cT1 N0 M0 NSCLC had limited isolated locoregional recurrences and outcomes similar to those in patients who underwent lobectomy. Lobectomy may not provide an advantage in these patients.

3.
Ann Surg ; 2024 May 10.
Article in English | MEDLINE | ID: mdl-38726663

ABSTRACT

OBJECTIVE: To assess the performance of a lower predicted postoperative (ppo) forced expiratory volume in 1 second (FEV1) or diffusion capacity of the lung for carbon monoxide (DLCO) (ppoFEV1/ppoDLCO) threshold to predict cardiopulmonary complications after minimally invasive surgery (MIS) lobectomy. SUMMARY BACKGROUND DATA: Although MIS is associated with better postoperative outcomes than open surgery, MIS uses risk-assessment algorithms developed for open surgery. Moreover, several different definitions of cardiopulmonary complications are used for assessment. METHODS: All patients who underwent MIS lobectomy for clinical stage I-II lung cancer from 2018 to 2022 at our institution were considered. The performance of a ppoFEV1/ppoDLCO threshold of <45% was compared against that of the current guideline threshold of <60%. Three different definitions of cardiopulmonary complications were compared: Society of Thoracic Surgeons (STS), European Society of Thoracic Surgeons (ESTS), and Berry et al. RESULTS: In 946 patients, the ppoFEV1/ppoDLCO threshold of <45% was associated with a higher proportion correctly classified (79% [95% CI, 76%-81%] vs. 65% [95% CI, 62%-68%]; P<0.001). The complication with the biggest difference in incidence between ppoFEV1/ppoDLCO of 45%-60% and >60% was prolonged air leak (33 [13%] vs. 34 [6%]; P<0.001). The predicted probability curves for cardiopulmonary complications were higher for the STS definition than for the ESTS or Berry definitions across ppoFEV1 and ppoDLCO values. CONCLUSIONS: The ppoFEV1/ppoDLCO threshold of <45% more accurately classified patients for cardiopulmonary complications after MIS lobectomy, emphasizing the need for updated risk-assessment guidelines for MIS lobectomy to optimize additional cardiopulmonary function evaluation.

4.
J Thorac Oncol ; 2024 May 16.
Article in English | MEDLINE | ID: mdl-38762120

ABSTRACT

INTRODUCTION: Electronic nose (E-nose) technology has reported excellent sensitivity and specificity in the setting of lung cancer screening. However, the performance of E-nose specifically for early-stage tumors remains unclear. Therefore, the aim of our study was to assess the diagnostic performance of E-nose technology in clinical stage I lung cancer. METHODS: This phase IIc trial (NCT04734145) included patients diagnosed with a single greater than or equal to 50% solid stage I nodule. Exhalates were prospectively collected from January 2020 to August 2023. Blinded bioengineers analyzed the exhalates, using E-nose technology to determine the probability of malignancy. Patients were stratified into three risk groups (low-risk, [<0.2]; moderate-risk, [≥0.2-0.7]; high-risk, [≥0.7]). The primary outcome was the diagnostic performance of E-nose versus histopathology (accuracy and F1 score). The secondary outcome was the clinical performance of the E-nose versus clinicoradiological prediction models. RESULTS: Based on the predefined cutoff (<0.20), E-nose agreed with histopathologic results in 86% of cases, achieving an F1 score of 92.5%, based on 86 true positives, two false negatives, and 12 false positives (n = 100). E-nose would refer fewer patients with malignant nodules to observation (low-risk: 2 versus 9 and 11, respectively; p = 0.028 and p = 0.011) than would the Swensen and Brock models and more patients with malignant nodules to treatment without biopsy (high-risk: 27 versus 19 and 6, respectively; p = 0.057 and p < 0.001). CONCLUSIONS: In the setting of clinical stage I lung cancer, E-nose agrees well with histopathology. Accordingly, E-nose technology can be used in addition to imaging or as part of a "multiomics" platform.

5.
Surg Oncol Clin N Am ; 33(3): 529-538, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38789195

ABSTRACT

Minimally invasive Ivor Lewis esophagectomy is a technically demanding operation that requires an experienced surgeon, assistant, and anesthesiologist. The preoperative workup should focus on the extent of disease and extent of resection required, as well as the cardiopulmonary fitness of the patient. Surgical outcomes show decreased postoperative pain, decreased morbidity largely due to a reduction in respiratory complications, and decreased length of stay. Quality metrics and 5-year overall survival are equivalent to traditional open esophagectomy.


Subject(s)
Esophageal Neoplasms , Esophagectomy , Minimally Invasive Surgical Procedures , Humans , Esophagectomy/methods , Esophageal Neoplasms/surgery , Minimally Invasive Surgical Procedures/methods , Laparoscopy/methods
6.
J Gastrointest Surg ; 28(4): 337-342, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38583881

ABSTRACT

BACKGROUND: The relationship among obesity, bariatric surgery, and esophageal adenocarcinoma (EAC) is complex, given that some bariatric procedures are thought to be associated with increased incidence of reflux and Barrett's esophagus. Previous bariatric surgery may complicate the use of the stomach as a conduit for esophagectomy. In this study, we presented our experience with patients who developed EAC after bariatric surgery and described the challenges encountered and the techniques used. METHODS: We conducted a retrospective review of our institutional database to identify all patients at our institution who were treated for EAC after previously undergoing bariatric surgery. RESULTS: In total, 19 patients underwent resection with curative intent for EAC after bariatric surgery, including 10 patients who underwent sleeve gastrectomy. The median age at diagnosis of EAC was 63 years; patients who underwent sleeve gastrectomy were younger (median age, 56 years). The median time from bariatric surgery to EAC was 7 years. Most patients had a body mass index (BMI) score of >30 kg/m2 at the time of diagnosis of EAC; approximately 40% had class III obesity (BMI score > 40 kg/m2). Six patients (32%) had known Barrett's esophagus before undergoing a reflux-increasing bariatric procedure. Sleeve gastrectomy patients underwent esophagectomy with gastric conduit, colonic interposition, or esophagojejunostomy. Only 1 patient had an anastomotic leak (after esophagojejunostomy). CONCLUSION: Endoscopy should be required both before (for treatment selection) and after all bariatric surgical procedures. Resection of EAC after bariatric surgery requires a highly individualized approach but is safe and feasible.


Subject(s)
Adenocarcinoma , Bariatric Surgery , Barrett Esophagus , Esophageal Neoplasms , Gastroesophageal Reflux , Obesity, Morbid , Humans , Middle Aged , Barrett Esophagus/etiology , Barrett Esophagus/surgery , Barrett Esophagus/diagnosis , Esophageal Neoplasms/etiology , Esophageal Neoplasms/surgery , Esophageal Neoplasms/diagnosis , Adenocarcinoma/etiology , Adenocarcinoma/surgery , Adenocarcinoma/diagnosis , Bariatric Surgery/adverse effects , Gastroesophageal Reflux/surgery , Gastroesophageal Reflux/complications , Obesity/complications , Obesity/surgery , Gastrectomy/adverse effects , Retrospective Studies , Obesity, Morbid/surgery
7.
Ann Thorac Surg ; 118(1): 130-140, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38408631

ABSTRACT

BACKGROUND: The current standard of care for locally advanced esophageal and gastroesophageal junction (GEJ) cancers includes neoadjuvant chemoradiotherapy or perioperative chemotherapy with surgical resection; however, disease-free survival in these patients remains poor. Immune checkpoint inhibitors (ICIs) are approved for adjuvant treatment of locally advanced esophageal and GEJ cancers, but their benefit in the perioperative and neoadjuvant settings remains under investigation. METHODS: We used the PubMed online database to conduct a literature search to identify studies that investigated immunotherapy for locally advanced esophageal and GEJ carcinoma. A review of ClinicalTrials.gov yielded a list of ongoing trials. RESULTS: Adjuvant nivolumab for residual disease after neoadjuvant chemoradiotherapy and surgery is the only approved immunotherapy regimen for locally advanced esophageal cancer. Early-phase trials investigating the addition of neoadjuvant or perioperative ICIs to standard-of-care multimodality approaches have observed pathologic complete response rates as high as 60%. Response rates are highest for ICIs plus chemoradiotherapy for esophageal squamous cell carcinoma and dual checkpoint inhibition in mismatch repair-deficient adenocarcinomas. Safety profiles are acceptable, with a pooled adverse event rate of 27%. Surgical morbidity and mortality with immunotherapy are similar to historical controls with no immunotherapy, and R0 resection rates are high. When reported, disease-free survival among patients treated with perioperative immunotherapy is promising. CONCLUSIONS: Outside of clinical trials, immunotherapy for resectable esophageal carcinoma is limited to the adjuvant setting. Phase III trials investigating neoadjuvant and perioperative immunotherapy are now underway and will provide much-needed data on survival that may ultimately lead to practice-changing recommendations.


Subject(s)
Esophageal Neoplasms , Immunotherapy , Humans , Esophageal Neoplasms/therapy , Esophageal Neoplasms/pathology , Immunotherapy/methods , Neoadjuvant Therapy/methods , Neoplasm Staging , Esophagectomy/methods , Immune Checkpoint Inhibitors/therapeutic use
9.
Mol Cancer Res ; 21(5): 397-410, 2023 05 01.
Article in English | MEDLINE | ID: mdl-36790391

ABSTRACT

A subset of thyroid cancers, recurrent differentiated thyroid cancers and anaplastic thyroid cancer (ATC), are difficult to treat by thyroidectomy and systemic therapy. A common mutation in thyroid cancer, BRAFV600E, has targetable treatment options; however, the results have been disappointing in thyroid cancers compared with BRAFV600E melanoma, as thyroid cancers quickly become resistant to BRAFV600E inhibitor (BRAFi). Here, we studied the molecular pathway that is induced in BRAFV600E thyroid cancer cells and patient-derived tumor samples in response to BRAFi, vemurafenib, using RNA-sequencing and molecular analysis. Both inducible response to BRAFi and acquired BRAFi resistance in BRAFV600E thyroid cancer cells showed significant activation of the JAK/STAT pathway. Functional analyses revealed that the combination of BRAFi and inhibitors of JAK/STAT pathway controlled BRAFV600E thyroid cancer cell growth. The Cancer Genome Atlas data analysis demonstrated that potent activation of the JAK/STAT signaling was associated with shorter recurrence rate in patients with differentiated thyroid cancer. Analysis of tumor RNA expression in patients with poorly differentiated thyroid cancer and ATC also support that enhanced activity of JAK/STAT signaling pathway is correlated with worse prognosis. Our study demonstrates that JAK/STAT pathway is activated as BRAFV600E thyroid cancer cells develop resistance to BRAFi and that this pathway is a potential target for anticancer activity and to overcome drug resistance that commonly develops to treatment with BRAFi in thyroid cancer. IMPLICATIONS: Dual inhibition of BRAF and JAK/STAT signaling pathway is a potential therapeutic treatment for anticancer activity and to overcome drug resistance to BRAFi in thyroid cancer.


Subject(s)
Thyroid Carcinoma, Anaplastic , Thyroid Neoplasms , Humans , Proto-Oncogene Proteins B-raf/metabolism , Janus Kinases/genetics , Janus Kinases/metabolism , Janus Kinases/therapeutic use , Sulfonamides/pharmacology , Signal Transduction , STAT Transcription Factors/genetics , STAT Transcription Factors/metabolism , STAT Transcription Factors/therapeutic use , Neoplasm Recurrence, Local/drug therapy , Thyroid Neoplasms/drug therapy , Thyroid Neoplasms/genetics , Thyroid Neoplasms/pathology , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Thyroid Carcinoma, Anaplastic/drug therapy , Thyroid Carcinoma, Anaplastic/genetics , Thyroid Carcinoma, Anaplastic/pathology , Mutation , RNA , Drug Resistance, Neoplasm/genetics , Cell Line, Tumor
10.
Ann Surg ; 277(1): 116-120, 2023 Jan 01.
Article in English | MEDLINE | ID: mdl-33351463

ABSTRACT

OBJECTIVE: We sought to evaluate the performance of 2 commonly used prediction models for postoperative morbidity in patients undergoing open and minimally invasive esophagectomy. SUMMARY BACKGROUND DATA: Patients undergoing esophagectomy have a high risk of postoperative complications. Accurate risk assessment in this cohort is important for informed decision-making. METHODS: We identified patients who underwent esophagectomy between January 2016 and June 2018 from our prospectively maintained database. Predicted morbidity was calculated using the American College of Surgeons National Surgical Quality Improvement Program Surgical Risk Calculator (SRC) and a 5-factor National Surgical Quality Improvement Programderived frailty index. Performance was evaluated using concordance index (C-index) and calibration curves. RESULTS: In total, 240 consecutive patients were included for analysis. Most patients (85%) underwent Ivor Lewis esophagectomy. The observed overall complication rate was 39%; the observed serious complication rate was 33%.The SRC did not identify risk of complications in the entire cohort (C-index, 0.553), patients undergoing open esophagectomy (C-index, 0.569), or patients undergoing minimally invasive esophagectomy (C-index, 0.542); calibration curves showed general underestimation. Discrimination of the SRC was lowest for reoperation (C-index, 0.533) and highest for discharge to a facility other than home (C-index, 0.728). Similarly, the frailty index had C-index of 0.513 for discriminating any complication, 0.523 for serious complication, and 0.559 for readmission. CONCLUSIONS: SRC and frailty index did not adequately predict complications after esophagectomy. Procedure-specific risk-assessment tools are needed to guide shared patient-physician decision-making in this high-risk population.


Subject(s)
Esophageal Neoplasms , Frailty , Humans , Esophagectomy/adverse effects , Frailty/complications , Retrospective Studies , Risk Assessment , Postoperative Complications/epidemiology , Decision Making , Esophageal Neoplasms/surgery
11.
Lancet Infect Dis ; 23(2): 207-221, 2023 02.
Article in English | MEDLINE | ID: mdl-36206793

ABSTRACT

BACKGROUND: Strategies to reduce antibiotic overuse in hospitals depend on prescribers taking decisions to stop unnecessary antibiotic use. There is scarce evidence for how to support these decisions. We evaluated a multifaceted behaviour change intervention (ie, the antibiotic review kit) designed to reduce antibiotic use among adult acute general medical inpatients by increasing appropriate decisions to stop antibiotics at clinical review. METHODS: We performed a stepped-wedge, cluster (hospital)-randomised controlled trial using computer-generated sequence randomisation of eligible hospitals in seven calendar-time blocks in the UK. Hospitals were eligible for inclusion if they admitted adult non-elective general or medical inpatients, had a local representative to champion the intervention, and could provide the required study data. Hospital clusters were randomised to an implementation date occurring at 1-2 week intervals, and the date was concealed until 12 weeks before implementation, when local preparations were designed to start. The intervention effect was assessed using data from pseudonymised routine electronic health records, ward-level antibiotic dispensing, Clostridioides difficile tests, prescription audits, and an implementation process evaluation. Co-primary outcomes were monthly antibiotic defined daily doses per adult acute general medical admission (hospital-level, superiority) and all-cause mortality within 30 days of admission (patient level, non-inferiority margin of 5%). Outcomes were assessed in the modified intention-to-treat population (ie, excluding sites that withdrew before implementation). Intervention effects were assessed by use of interrupted time series analyses within each site, estimating overall effects through random-effects meta-analysis, with heterogeneity across prespecified potential modifiers assessed by use of meta-regression. This trial is completed and is registered with ISRCTN, ISRCTN12674243. FINDINGS: 58 hospital organisations expressed an interest in participating. Three pilot sites implemented the intervention between Sept 25 and Nov 20, 2017. 43 further sites were randomised to implement the intervention between Feb 12, 2018, and July 1, 2019, and seven sites withdrew before implementation. 39 sites were followed up for at least 14 months. Adjusted estimates showed reductions in total antibiotic defined daily doses per acute general medical admission (-4·8% per year, 95% CI -9·1 to -0·2) following the intervention. Among 7 160 421 acute general medical admissions, the ARK intervention was associated with an immediate change of -2·7% (95% CI -5·7 to 0·3) and sustained change of 3·0% (-0·1 to 6·2) in adjusted 30-day mortality. INTERPRETATION: The antibiotic review kit intervention resulted in sustained reductions in antibiotic use among adult acute general medical inpatients. The weak, inconsistent intervention effects on mortality are probably explained by the onset of the COVID-19 pandemic. Hospitals should use the antibiotic review kit to reduce antibiotic overuse. FUNDING: UK National Institute for Health and Care Research.


Subject(s)
Anti-Bacterial Agents , Hospitals , Adult , Humans , Anti-Bacterial Agents/therapeutic use , COVID-19 , Hospitalization , Pandemics
12.
Spinal Cord ; 61(1): 1-7, 2023 01.
Article in English | MEDLINE | ID: mdl-35962043

ABSTRACT

STUDY DESIGN: Systematic review. OBJECTIVES: To systematically review the evidence on the use of local analgesics, specifically lidocaine or bupivacaine, to prevent autonomic dysreflexia (AD) during iatrogenic procedures or bowel and bladder care routines in individuals with spinal cord injury (SCI). METHODS: A keyword search of MEDLINE, CINAHL, CENTRAL, Cochrane Reviews, PsycInfo, Embase, and Web of Science databases identified all English-language studies evaluating the efficacy of local analgesics in reducing AD. Included studies were either randomized controlled trials (RCTs) or quasi-experimental studies. Participants were adults with chronic SCI who received local analgesics prior to AD-triggering procedures or routines. Additionally, studies were required to report blood pressure values as an outcome. The methodology of this review followed the PRISMA checklist and was registered with PROSPERO (CRD42021219506). RESULTS: Four RCTs and two quasi-experimental studies met inclusion criteria. Results were narratively synthesized as meta-analysis was not possible due to heterogeneity across studies included in the review. All six studies administered lidocaine. Lidocaine was found to have a beneficial effect on AD in three studies, no effect in two studies and a detrimental effect in one study. CONCLUSIONS: Presently, RCTs and quasi-experimental studies on the use of lidocaine for reducing AD in individuals with SCI had small sample sizes and opposing findings. There is a strong need for definitive, well-monitored clinical trials with adequate sample sizes. Presently there is not enough compelling evidence to support or refute recommendations for the use of lidocaine from the AD management clinical practice guidelines.


Subject(s)
Autonomic Dysreflexia , Spinal Cord Injuries , Adult , Humans , Autonomic Dysreflexia/drug therapy , Autonomic Dysreflexia/etiology , Autonomic Dysreflexia/prevention & control , Spinal Cord Injuries/complications , Spinal Cord Injuries/drug therapy , Lidocaine/therapeutic use , Bupivacaine , Analgesics/therapeutic use
13.
J Endocrinol ; 255(2): 61-74, 2022 11 01.
Article in English | MEDLINE | ID: mdl-35938697

ABSTRACT

The profound programming effects of early life stress (ELS) on brain and behavior are thought to be primarily mediated by adrenal glucocorticoids (GCs). However, in mice, stressors are often administered between postnatal days 2 and 12 (PND2-12), during the stress hyporesponsive period (SHRP), when adrenal GC production is greatly reduced at baseline and in response to stressors. During the SHRP, specific brain regions produce GCs at baseline, but it is unknown if brain GC production increases in response to stressors. We treated mice at PND1 (pre-SHRP), PND5 (SHRP), PND9 (SHRP), and PND13 (post-SHRP) with an acute stressor (isoflurane anesthesia), vehicle control (oxygen), or neither (baseline). We measured a panel of progesterone and six GCs in the blood, hippocampus, cerebral cortex, and hypothalamus via liquid chromatography tandem mass spectrometry. At PND1, baseline corticosterone levels were high and did not increase in response to stress. At PND5, baseline corticosterone levels were very low, increases in brain corticosterone levels were greater than the increase in blood corticosterone levels, and stress had region-specific effects. At PND9, baseline corticosterone levels were low and increased similarly and moderately in response to stress. At PND13, blood corticosterone levels were higher than those at PND9, and corticosterone levels were higher in blood than in brain regions. These data illustrate the rapid and profound changes in stress physiology during neonatal development and suggest that neurosteroid production is a possible mechanism by which ELS has enduring effects on brain and behavior.


Subject(s)
Corticosterone , Isoflurane , Animals , Animals, Newborn , Brain , Glucocorticoids , Isoflurane/pharmacology , Mice , Stress, Psychological
14.
J Surg Res ; 279: 77-83, 2022 11.
Article in English | MEDLINE | ID: mdl-35724546

ABSTRACT

INTRODUCTION: The incidence of papillary thyroid cancer (PTC) in the United States has tripled in the past 30 y. Polybrominated diphenyl ethers (PBDEs) are flame retardants that were ubiquitously used over that time period, and exposure to PBDEs has been associated with PTC prevalence. They are potential carcinogens via their induction of reactive oxygen species (ROS) formation and resultant deoxyribonucleic acid (DNA) damage. We sought to determine the effects of PBDE and tris(2-chloroethyl) phosphate (TCEP), another flame retardant implicated in PTC incidence, on thyrocytes in vitro and measure PBDE levels in human thyroid tissue to determine their carcinogenic potential. METHODS: Nthy-Ori, an immortalized benign human thyroid follicular cell line was used as a model of normal human thyroid. MTT assays were used to measure cell viability after exposure to PBDEs and TCEP. ROS levels and double-stranded and single-stranded DNA breaks were measured to determine genotoxicity. DNA damage response protein levels were measured with immunoblotting. RESULTS: Exposure to 20µM PBDE or TCEP for 48 h had minimal effects on thyrocyte viability. There was no significant increase in intracellular ROS up to 6 h following PBDE or TCEP exposure in thyrocytes; however, cells exposed to PBDE 47 showed evidence of DNA single-stranded and double-stranded breaks. There was a dose-dependent increase in γH2AX levels following exposure to PBDEs 47 and 209 in Nthy-Ori cells but not with TCEP treatment. CONCLUSIONS: PBDE 47 and 209 demonstrated genotoxicity but not cytotoxicity in follicular thyrocytes in vitro. Therefore, PBDE 47 and 209 may be carcinogenic in human thyroid cells.


Subject(s)
Flame Retardants , Halogenated Diphenyl Ethers , Carcinogens , Flame Retardants/toxicity , Halogenated Diphenyl Ethers/toxicity , Humans , Organophosphates , Phosphates , Phosphines , Reactive Oxygen Species , Thyroid Gland
15.
EJNMMI Res ; 12(1): 29, 2022 May 12.
Article in English | MEDLINE | ID: mdl-35553267

ABSTRACT

BACKGROUND: Despite its widespread use, the semi-quantitative standardized uptake value ratio (SUVR) may be biased compared with the distribution volume ratio (DVR). This bias may be partially explained by changes in cerebral blood flow (CBF) and is likely to be also dependent on the extent of the underlying amyloid-ß (Aß) burden. This study aimed to compare SUVR with DVR and to evaluate the effects of underlying Aß burden and CBF on bias in SUVR in mainly cognitively unimpaired participants. Participants were scanned according to a dual-time window protocol, with either [18F]flutemetamol (N = 90) or [18F]florbetaben (N = 31). The validated basisfunction-based implementation of the two-step simplified reference tissue model was used to derive DVR and R1 parametric images, and SUVR was calculated from 90 to 110 min post-injection, all with the cerebellar grey matter as reference tissue. First, linear regression and Bland-Altman analyses were used to compare (regional) SUVR with DVR. Then, generalized linear models were applied to evaluate whether (bias in) SUVR relative to DVR could be explained by R1 for the global cortical average (GCA), precuneus, posterior cingulate, and orbitofrontal region. RESULTS: Despite high correlations (GCA: R2 ≥ 0.85), large overestimation and proportional bias of SUVR relative to DVR was observed. Negative associations were observed between both SUVR or SUVRbias and R1, albeit non-significant. CONCLUSION: The present findings demonstrate that bias in SUVR relative to DVR is strongly related to underlying Aß burden. Furthermore, in a cohort consisting mainly of cognitively unimpaired individuals, the effect of relative CBF on bias in SUVR appears limited. EudraCT Number: 2018-002277-22, registered on: 25-06-2018.

17.
J Thorac Cardiovasc Surg ; 163(4): 1509-1516.e1, 2022 04.
Article in English | MEDLINE | ID: mdl-33610360

ABSTRACT

OBJECTIVE: The American College of Surgeons National Surgical Quality Improvement Program Surgical Risk Calculator (NSQIP SRC) was developed to estimate the risk of postoperative morbidity and mortality within 30 days of an operation. We sought to externally evaluate the performance of the NSQIP SRC for patients undergoing pulmonary resection. METHODS: Patients undergoing pulmonary resection at our center between January 2016 and December 2018 were included. Using data from our institution's prospectively maintained Society of Thoracic Surgeons General Thoracic Database, we identified 2514 patients. We entered requisite patient demographic information, preoperative risk factors, and procedural details into the online calculator. Predicted performance of the calculator versus observed outcomes was assessed by discrimination (concordance index [C-index]) and calibration. RESULTS: The observed and predicted probabilities of any complication were 8.3% and 9.9%, respectively, and of serious complications were 7.4% and 9.2%, respectively. Observed and predicted 30-day mortality were 0.5% and 0.9%, respectively. The C-index for readmission was 0.644; the C-indices corresponding to all other outcomes in the NSQIP SRC ranged from 0.703 to 0.821. Calibration curves indicated excellent calibration for all binary end points, with the exception of renal failure (predicted underestimated observed probabilities), discharge to a nursing or rehabilitation facility (overestimated), and sepsis (overestimated). Correlation between predicted and observed length of stay was moderate (Spearman coefficient, 0.562), and calibration was good. CONCLUSIONS: Except for readmission, renal failure, discharge to a location other than home, and sepsis, the NSQIP SRC can be used to reasonably predict postoperative complications in patients undergoing pulmonary resection.


Subject(s)
Pneumonectomy , Postoperative Complications , Risk Assessment , Acute Kidney Injury , Aged , Aged, 80 and over , Female , Humans , Length of Stay , Male , Patient Discharge , Patient Readmission , Prognosis
19.
Ann Thorac Surg ; 113(4): 1112-1118, 2022 04.
Article in English | MEDLINE | ID: mdl-34403692

ABSTRACT

BACKGROUND: Readmission after coronary artery bypass grafting (CABG) is associated with adverse outcomes and increased cost. We evaluated the impact of a high-value care discharge protocol on readmission, length of stay (LOS), and discharge destination in patients undergoing isolated CABG. METHODS: In 2016, a comprehensive, patient-centered discharge protocol was implemented. A nurse practitioner was the fulcrum of this program, which focused on improving health literacy, disease management, and rigorous follow-up. All patients undergoing isolated CABG between 2012 and 2019 were retrospectively analyzed with regard to 30-day readmission, LOS, and discharge disposition. Differences were analyzed by Mann-Whitney, chi-square, and t tests. Analyses were repeated using propensity matching. RESULTS: A total of 910 consecutive patients undergoing isolated CABG were included in the analyses: 353 preprotocol and 557 postprotocol. Preprotocol patients had a readmission rate of 14.4% (n = 51), compared with 6.8% (n = 38) in the postprotocol patients (P < .001). Median postoperative LOS before implementation was 6 (interquartile range, 5-8) days compared with 5 (interquartile range, 4-6) days postimplementation (P < .001). Postimplementation, a higher proportion of patients were discharged to home compared with a skilled nursing facility (82.7% [n = 461] vs 73.9% [n = 261]; P = .002). After propensity matching, 298 well-balanced patients were included for analysis and these significant reductions in LOS, readmission, and discharge destination persisted. CONCLUSIONS: Implementation of a new discharge protocol was significantly associated with reduced readmission and LOS, along with higher rates of discharge to home in isolated CABG patients. Importantly, the results were sustainable and did not require additional resources, delivering high-value care.


Subject(s)
Patient Discharge , Patient Readmission , Coronary Artery Bypass/adverse effects , Humans , Length of Stay , Postoperative Complications/etiology , Retrospective Studies , Risk Factors
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