Search

Purpose: The purpose of this study was to describe the incidence of corneal graft rejection after COVID and influenza vaccination., Methods: Patients 65 years or older undergoing penetrating keratoplasty or endothelial keratoplasty any time between 2016 and 2021 followed by COVID or influenza vaccination in 2021 among the 100% Medicare Fee-For-Service database were included. Demographic and ocular history characteristics of patients with (cases) and without graft rejection (controls) were compared using the χ2 test., Results: After COVID (n = 31,398) and influenza (n = 24,290) vaccination, 0.45% (n = 140) and 0.17% (n = 41) patients developed rejection within 90 days, respectively. There was no difference in the rate of graft rejection within 90 days relative to 90 to 180 days after vaccination after both COVID (90 days: 0.45% vs. 180 days: 0.61%, P = 0.37) and influenza (90 days: 0.17% vs. 180 days: 0.29%, P = 0.11) vaccines. For COVID vaccination, patients who underwent penetrating keratoplasty (n = 51, 0.97%; vs. endothelial keratoplasty = 89; 0.34%, P < 0.001), history of rejection up to 1 year before vaccination (n = 13; 1.30% vs. no history = 127, 0.42%; P < 0.001), and having an ocular comorbidity (n = 110, 0.54% vs. no ocular comorbidity = 30, 0.27%; P = 0.001) had higher rates of graft rejections, and most rejections were after 1 year postkeratoplasty (87.14%, n = 122)., Conclusions: The incidence of graft rejection postvaccination is low compared with the overall rates of rejection in the published literature. Most post-COVID vaccination graft rejections were after 1 year postkeratoplasty when corticosteroids are expected to have been tapered to lower doses. Surgeons may counsel patients regarding graft rejection symptoms, but overall low rates may not warrant pretreatment in low-risk keratoplasty patients., Competing Interests: M. A. Makary is on the board of Harrow Health Inc. Other authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis. Identifying modifiable risk factors, such as diabetes, is crucial. In the context of PDAC diagnosis, diabetes manifests as long-term (LTD), new-onset (NOD), or postsurgical (PSD) phenotypes. The link between these diabetes phenotypes and PDAC survival is debated., Materials and Methods: We performed a retrospective study on patients with resectable PDAC who underwent pancreatectomy at Johns Hopkins Hospital from 2003 to 2017. We utilized the National Death Index and electronic medical records to determine vital status. We categorized diabetes as LTD, NOD, or PSD based on the timing of diagnosis relative to pancreatic resection. Using multivariable Cox models, we assessed hazard ratios (HRs) for survival times associated with each phenotype, considering known PDAC prognostic factors., Results: Of 1556 patients, the 5-year survival was 19% (95% CI, 17-21). No significant survival differences were observed between diabetes phenotypes and non-diabetic patients. NOD and PSD presented nonsignificant increased risks of death (aHR: 1.14 [95% CI, 0.8-1.19] and 1.05 [95% CI, 0.89-1.25], respectively). LTD showed no survival difference (aHR, 0.98; 95% CI, 0.99-1.31)., Conclusions: No link was found between diabetes phenotypes and survival in resectable PDAC patients. Comprehensive prospective studies are required to validate these results., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: Fat quality and quantity may affect health similarly or differently. Fat quality can be assessed by measuring fat density on CT scan (greater density = smaller, higher quality adipocytes). We assessed the effects of tesamorelin, a growth hormone-releasing hormone analogue that reduces visceral fat (VAT) quantity in some people living with HIV (PWH), on fat density., Design: Participants from two completed, placebo-controlled, randomized trials of tesamorelin for central adiposity treatment in PWH were included if they had either a clinical response to tesamorelin (VAT decrease ≥8%, ≈70% of participants) or were placebo-treated., Methods: CT VAT and subcutaneous fat (SAT) density (Hounsfield Units, HU) were measured by a central blinded reader., Results: Participants (193 responders, 148 placebo) were 87% male and 83% white. Baseline characteristics were similar across arms, including VAT (-91 HU both arms, P = 0.80) and SAT density (-94 HU tesamorelin, -95 HU placebo, P = 0.29). Over 26 weeks, mean (SD) VAT and SAT density increased in tesamorelin-treated participants only [VAT: +6.2 (8.7) HU tesamorelin, +0.3 (4.2) HU placebo, P < 0.0001; SAT: +4.0 (8.7) HU tesamorelin, +0.3 (4.8) HU placebo, P < 0.0001]. The tesamorelin effects persisted after controlling for baseline VAT or SAT HU and area, and VAT [+2.3 HU, 95% confidence interval (4.5-7.3), P = 0.001) or SAT (+3.5 HU, 95% confidence interval (2.3-4.7), P < 0.001] area change., Conclusion: In PWH with central adiposity who experienced VAT quantity reductions on tesamorelin, VAT and SAT density increased independent of changes in fat quantity, suggesting that tesamorelin also improves VAT and SAT quality in this group., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The purpose of this study was to assess the temporal trends in 30-day mortality by race group for patients undergoing coronary artery bypass grafting (CABG) between 2011 and 2018 and to investigate the effect of race and sex on postoperative outcomes after CABG., Summary Background Data: Cardiovascular diseases remain a leading cause of death in the United States with studies demonstrating increased morbidity and mortality for black and female patients undergoing surgery. In the post drug-eluting stent era, studies of racial disparities CABG are outdated., Methods: We performed a retrospective analysis of the Society for Thoracic Surgeons database for patients undergoing CABG between 2011 and 2018. Primary outcome was 30-day mortality. Secondary outcomes included postoperative length of stay, surgical site infection, sepsis, pneumonia, stroke, reoperation, reintervention, early extubation, and readmission., Results: The study population was comprised of 1,042,506 patients who underwent isolated CABG between 2011 and 2018. Among all races, Black patients had higher rates of preoperative comorbidities. Compared with White patients, Black patients had higher overall mortality (2.76% vs 2.19%, P < 0.001). On univariable regression, Black patients had higher rates of death, infection, pneumonia, and postoperative stroke compared to White patients. On multivariable regression, Black patients had higher odds of 30-day mortality compared to white patients [odds ratio (OR) = 1.11, 95% confidence interval (CI) 1.05-1.18]. Similarly, female patients had higher odds of death compared to males (OR = 1.26, 95% CI 1.21-1.30)., Conclusions: In the modern era, racial and sex disparities in mortality and postoperative morbidity after coronary bypass surgery persist with Black patients and female patients consistently experiencing worse outcomes than White male patients. Although there may be unknown or underappreciated biological mechanisms at play, future research should focus on socioeconomic, cultural, and multilevel factors.

Background: The epidemic of nonmedical use of prescription opioids (NMUPOs) has been fueled in part by the availability of leftover, legitimately prescribed opioids. In children, outpatient urological procedures are among the most common surgeries performed, but data are lacking to guide appropriate postoperative opioid prescribing. The aim of this study was to compare the amount of prescribed opioid medication to the amount taken for acute pain after minor pediatric urological surgery and to determine the disposition of excess opioid. In addition, we explored whether distinct patient characteristics and procedure type influenced opioid prescribing and consumption., Methods: Of the 139 families of pediatric patients enrolled, 115 were interviewed within 48 hours and/or 10-14 days of discharge to determine the amount of opioid prescribed and consumed, duration of treatment, and disposition of unconsumed opioid., Results: The most common procedures performed were circumcision (n = 58) and orchiopexy (n = 40). Most patients (98%) were male, and 77% were <8 years of age. All opioid prescriptions were for oxycodone dosed every 4 hours as needed (PRN). Median number of doses prescribed was 30 (interquartile range [IQR], 23-31; n = 138) for both respondents who reported doses remaining (IQR, 29-31; n = 83) and those who did not (IQR, 22-32; n = 55). Among those reporting doses remaining, median number of doses consumed was 4.2 (IQR, 0-14). Multivariable linear regression showed no significant association between doses consumed and patient age, type of procedure, discharge pain score, or use of adjuvant analgesics. Median duration of opioid therapy was 2 days (IQR, 0-5; n = 83) with each additional day of opioid use corresponding to an average increase in consumption of 2.3 doses (95% confidence interval [CI], 1.8-2.8). An estimated 75% (95% CI, 69%-81%) of opioid dispensed was not consumed, and 86% (72/83) of patients took ≤18 doses. Forty-four of 65 (68%) families reported receiving no disposal instructions for leftover opioid, and only 7 families disposed of leftover medication., Conclusions: For minor pediatric urological surgeries in young boys, a 3-day supply (18 doses) of opioid was sufficient to adequately treat acute postoperative pain in most patients. Adjusting opioid dispensing to align with consumption and better educating patients and families on opioid disposal can be used to potentially decrease availability of leftover opioids in homes and communities.

Background: Impaired cerebral blood flow (CBF) autoregulation during cardiopulmonary bypass (CPB) is associated with stroke and other adverse outcomes. Large and small arterial stenosis is prevalent in patients undergoing cardiac surgery. We hypothesize that large and/or small vessel cerebral arterial disease is associated with impaired cerebral autoregulation during CPB., Methods: A retrospective cohort analysis of data from 346 patients undergoing cardiac surgery with CPB enrolled in an ongoing prospectively randomized clinical trial of autoregulation monitoring were evaluated. The study protocol included preoperative transcranial Doppler (TCD) evaluation of major cerebral artery flow velocity by a trained vascular technician and brain magnetic resonance imaging (MRI) between postoperative days 3 and 5. Brain MRI images were evaluated for chronic white matter hyperintensities (WMHI) by a vascular neurologist blinded to autoregulation data. "Large vessel" cerebral vascular disease was defined by the presence of characteristic TCD changes associated with stenosis of the major cerebral arteries. "Small vessel" cerebral vascular disease was defined based on accepted scoring methods of WMHI. All patients had continuous TCD-based autoregulation monitoring during surgery., Results: Impaired autoregulation occurred in 32.4% (112/346) of patients. Preoperative TCD demonstrated moderate-severe large vessel stenosis in 67 (25.2%) of 266 patients with complete data. In adjusted analysis, female sex (odds ratio [OR], 0.46; 95% confidence interval [CI], 0.25-0.86; P = .014) and higher average temperature during CPB (OR, 1.23; 95% CI, 1.02-1.475; P = .029), but not moderate-severe large cerebral arterial stenosis (P = .406), were associated with impaired autoregulation during CPB. Of the 119 patients with available brain MRI data, 42 (35.3%) demonstrated WMHI. The presence of small vessel cerebral vascular disease was associated with impaired CBF autoregulation (OR, 3.25; 95% CI, 1.21-8.71; P = .019) after adjustment for age, history of peripheral vascular disease, preoperative hemoglobin level, and preoperative treatment with calcium channel blocking drugs., Conclusions: These data confirm that impaired CBF autoregulation is prevalent during CPB predisposing affected patients to brain hypoperfusion or hyperperfusion with low or high blood pressure, respectively. Small vessel, but not large vessel, cerebral vascular disease, male sex, and higher average body temperature during CPB appear to be associated with impaired autoregulation.

Background: The epidemic of nonmedical use of prescription opioids has been fueled by the availability of legitimately prescribed unconsumed opioids. The aim of this study was to better understand the contribution of prescriptions written for pediatric patients to this problem by quantifying how much opioid is dispensed and consumed to manage pain after hospital discharge, and whether leftover opioid is appropriately disposed of. Our secondary aim was to explore the association of patient factors with opioid dispensing, consumption, and medication remaining on completion of therapy., Methods: Using a scripted 10-minute interview, parents of 343 pediatric inpatients (98% postoperative) treated at a university children's hospital were questioned within 48 hours and 10 to 14 days after discharge to determine amount of opioid prescribed and consumed, duration of treatment, and disposition of unconsumed opioid. Multivariable linear regression was used to examine predictors of opioid prescribing, consumption, and doses remaining., Results: Median number of opioid doses dispensed was 43 (interquartile range, 30-85 doses), and median duration of therapy was 4 days (interquartile range, 1-8 days). Children who underwent orthopedic or Nuss surgery consumed 25.42 (95% confidence interval, 19.16-31.68) more doses than those who underwent other types of surgery (P < .001), and number of doses consumed was positively associated with higher discharge pain scores (P = .032). Overall, 58% (95% confidence interval, 54%-63%) of doses dispensed were not consumed, and the strongest predictor of number of doses remaining was doses dispensed (P < .001). Nineteen percent of families were informed how to dispose of leftover opioid, but only 4% (8 of 211) did so., Conclusions: Pediatric providers frequently prescribed more opioid than needed to treat pain. This unconsumed opioid may contribute to the epidemic of nonmedical use of prescription opioids. Our findings underscore the need for further research to develop evidence-based opioid prescribing guidelines for physicians treating acute pain in children.

Objective: To determine safety and perform a preliminary assessment of dose-dependent efficacy of dextromethorphan in normalizing electrographic spikes, clinical seizures, and behavioral and cognitive functions in girls with Rett syndrome., Methods: We used a prospective randomized, open-label trial in fast metabolizers of dextromethorphan to examine the effect of dextromethorphan on core clinical features of Rett syndrome. Interictal spike activity and clinical seizures were determined using EEG and parent reporting. Cognitive data were obtained using the Mullen Scales of Early Learning and Vineland Adaptive Behavior Scales, while behavioral data were obtained from parent-completed checklists, the Aberrant Behavior Checklist-Community Version, and the Screen for Social Interaction. Anthropometric data were obtained according to the National Health and Nutrition Examination Survey. The Rett Syndrome Severity Scale provided a clinical global impression of the effect of dextromethorphan on clinical severity., Results: Dextromethorphan is safe for use in 3- to 15-year-old girls with Rett syndrome. Thirty-five girls were treated with 1 of 3 doses of dextromethorphan over a period of 6 months. Statistically significant dose-dependent improvements were seen in clinical seizures, receptive language, and behavioral hyperactivity. There was no significant improvement in global clinical severity as measured by the Rett Syndrome Severity Scale., Conclusions: Dextromethorphan is a potent noncompetitive antagonist of the NMDA receptor channel that is safe for use in young girls with Rett syndrome. Preliminary evidence suggests that dextromethorphan may improve some core features of Rett syndrome., Classification of Evidence: This study provides Class IV evidence that dextromethorphan at various doses does not change EEG spike counts over 6 months, though precision was limited to exclude an important effect., (© 2017 American Academy of Neurology.)

Background: The purpose of this multicenter pilot study was to: (1) determine the frequency of regional cerebral oxygen saturation (rScO2) desaturations during cardiac surgery involving cardiopulmonary bypass (CPB); (2) evaluate the accuracy of clinician-identified rScO2 desaturations compared with those recorded continuously during surgery by the near-infrared spectroscopy (NIRS) monitor; and (3) assess the effectiveness of an intervention algorithm for reversing rScO2 desaturations., Methods: Two hundred thirty-five patients undergoing coronary artery bypass graft and/or valvular surgery were enrolled at 8 US centers in this prospective observational study. NIRS (Invos™ 5100C; Covidien) was used to monitor rScO2 during surgery. The frequency and magnitude of rScO2 decrements >20% from preanesthesia baseline were documented, and the efficacy of a standard treatment algorithm for correcting rScO2 was determined. The data from the NIRS monitor were downloaded at the conclusion of surgery and sent to the coordinating center where the number of clinician-identified rScO2 desaturation events was compared with the number detected by the NIRS monitor., Results: The average rScO2 obtained at baseline (mean ± SD, 61% ± 11%; 99% confidence interval, 57%-65%) and during CPB (62% ± 14%; 57%-67%) was not different. However, rScO2 after separation from CPB (56% ± 11%; 53%-60%) was lower than measurements at baseline and during CPB (P < 0.001). During CPB, rScO2 desaturations occurred in 61% (99% confidence interval, 50%-75%) of patients. The area under the curve for product of magnitude and duration of the rScO2 was (mean ± SD, 145.2; 384.8% × min). Clinicians identified all patients with an rScO2 desaturation but identified only 340 (89.5%) of the 380 total desaturation events. Of the 340 clinician-identified rScO2 desaturation events, 115 resolved with usual clinical care before implementation of the treatment algorithm. For the remaining 225 events, the treatment algorithm resulted in resolution of the rScO2 desaturation in all but 18 patients., Conclusions: This multicenter pilot study found that 50% to 75% of patients undergoing cardiac surgery experience one or more rScO2 desaturations during CPB. Nearly 10% of desaturation events were not identified by clinicians, suggesting that appropriate alarming systems should be adopted to alert clinicians of such events. The intervention algorithm was effective in reversing clinically identified rScO2 desaturations in the majority of events.

Background: About half of survivors with stroke experience severe and significant long-term disability. The purpose of this article is to review the state of the science and to make recommendations for measuring patient-centric outcomes in interventions for motor improvement in the chronic stroke phase., Methods and Results: A 9-member expert panel reviewed evidence to identify measures of upper and lower extremity function used to date as outcomes in trials with patients who experienced a stroke ≥6 months before assessment. Outcome measures were screened using StrokEDGE consensus panel recommendations, and evaluated for availability of a published minimal clinically important difference. Measures meeting these criteria were further evaluated with regard to their level of measurement, psychometric properties, and ability of minimal clinically important difference to capture gains associated with improved function and clinical relevance to patients, to arrive at recommendations. A systematic literature review yielded 115 clinical trials of upper and lower extremity function in chronic stroke that used a total of 34 outcome measures. Seven of these had published minimal clinically important differences and were recommended or highly recommended by StrokEDGE. Those are the Fugl-Meyer Upper Extremity and Lower Extremity scales, Wolf Motor Function Test, Action Research Arm Test, Ten-Meter and Six-Minute Walk Tests, and the Stroke Impact Scale. All had evidence for their psychometric performance, although the strength of evidence for validity varied, especially in populations with chronic stroke Fugl-Meyer Upper and Lower Extremity scales showing the strongest evidence for validity., Conclusions: The panel recommends that the Fugl-Meyer Upper and Lower Extremity scales be used as primary outcomes in intervention trials targeting motor function in populations with chronic stroke. The other 6 measures are recommended as secondary outcomes., (© 2015 American Heart Association, Inc.)

Background: Although controversial, failing to consider the gravitational effects of head elevation on cerebral perfusion is speculated to increase susceptibility to rare, but devastating, neurologic complications after shoulder surgery in the beach chair position (BCP). We hypothesized that patients in the BCP have diminished cerebral blood flow autoregulation than those who undergo surgery in the lateral decubitus position (LDP). A secondary aim was to examine whether there is a relationship between patient positioning during surgery and postoperative cognition or serum brain injury biomarker levels., Methods: Patients undergoing shoulder surgery in the BCP (n = 109) or LDP (n = 109) had mean arterial blood pressure (MAP) and regional cerebral oxygen saturation (rScO2) monitored with near-infrared spectroscopy. A continuous, moving Pearson correlation coefficient was calculated between MAP and rScO2, generating the variable cerebral oximetry index (COx). When MAP is in the autoregulated range, COx approaches zero because there is no correlation between cerebral blood flow and arterial blood pressure. In contrast, when MAP is below the limit of autoregulation, COx is higher because there is a direct relationship between lower arterial blood pressure and lower cerebral blood flow. Thus, diminished autoregulation would be manifest as higher COx. Psychometric testing was performed before surgery and then 7 to 10 days and 4 to 6 weeks after surgery. A composite cognitive outcome was determined as the Z-score. Serum S100β, neuron-specific enolase, and glial fibrillary acidic protein were measured at baseline, after surgery, and on postoperative day 1., Results: After adjusting for age and history of hypertension, COx (P = 0.035) was higher and rScO2 lower (P < 0.0001) in the BCP group than in the LDP group. After adjusting for baseline composite cognitive outcome, there was no difference in Z-score 7 to 10 days (P = 0.530) or 4 to 6 weeks (P = 0.202) after surgery between the BCP and the LDP groups. There was no difference in serum biomarker levels between the 2 position groups, Conclusions: : Compared with patients in the LDP, patients undergoing shoulder surgery in the BCP are more likely to have higher COx indicating diminished cerebral autoregulation and lower rScO2. There were no differences in the composite cognitive outcome between the BCP and the LDP groups after surgery after accounting for baseline Z-score.

Background: Mean arterial blood pressure (MAP) targets are empirically chosen during cardiopulmonary bypass (CPB). We have previously shown that near-infrared spectroscopy (NIRS) can be used clinically for monitoring cerebral blood flow autoregulation. The hypothesis of this study was that real-time autoregulation monitoring using NIRS-based methods is more accurate for delineating the MAP at the lower limit of autoregulation (LLA) during CPB than empiric determinations based on age, preoperative history, and preoperative blood pressure., Methods: Two hundred thirty-two patients undergoing coronary artery bypass graft and/or valve surgery with CPB underwent transcranial Doppler monitoring of the middle cerebral arteries and NIRS monitoring. A continuous, moving Pearson correlation coefficient was calculated between MAP and cerebral blood flow velocity and between MAP and NIRS data to generate mean velocity index and cerebral oximeter index. When autoregulated, there is no correlation between cerebral blood flow and MAP (i.e., mean velocity and cerebral oximetry indices approach 0); when MAP is below the LLA, mean velocity and cerebral oximetry indices approach 1. The LLA was defined as the MAP at which mean velocity index increased with declining MAP to ≥ 0.4. Linear regression was performed to assess the relation between preoperative systolic blood pressure, MAP, MAP in 10% decrements from baseline, and average cerebral oximetry index with MAP at the LLA., Results: The MAP at the LLA was 66 mm Hg (95% prediction interval, 43 to 90 mm Hg) for the 225 patients in which this limit was observed. There was no relationship between preoperative MAP and the LLA (P = 0.829) after adjusting for age, gender, prior stroke, diabetes, and hypertension, but a cerebral oximetry index value of >0.5 was associated with the LLA (P = 0.022). The LLA could be identified with cerebral oximetry index in 219 (94.4%) patients. The mean difference in the LLA for mean velocity index versus cerebral oximetry index was -0.2 ± 10.2 mm Hg (95% CI, -1.5 to 1.2 mm Hg). Preoperative systolic blood pressure was associated with a higher LLA (P = 0.046) but only for those with systolic blood pressure ≤ 160 mm Hg., Conclusions: There is a wide range of MAP at the LLA in patients during CPB, making estimation of this target difficult. Real-time monitoring of autoregulation with cerebral oximetry index may provide a more rational means for individualizing MAP during CPB.