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Alexander D Stoker,1 David M Rosenfeld,1 Matthew R Buras,2 Jeremy M Alvord,1 Andrew W Gorlin1 1Department of Anesthesiology and Perioperative Medicine, Mayo Clinic Arizona, Phoenix, AZ, USA; 2Mayo Clinic Arizona, Phoenix, AZ, USACorrespondence: Alexander D StokerDepartment of Anesthesiology and Perioperative Medicine, Mayo Clinic Arizona, 5777 E Mayo Blvd, Phoenix, AZ 85054, USATel +1 480-510-7933Email Stoker.Alexander@mayo.eduIntroduction: Sub-anesthetic ketamine is frequently used as an analgesic to reduce perioperative opioid consumption and has also been shown to have antidepressant effects. Side effects of ketamine include dizziness, diplopia, nystagmus, and psychomimetic effects. It is unclear what clinical factors may be associated with ketamine-related adverse drug events (ADEs).Methods: We performed a retrospective review of 95 patients who received sub-anesthetic ketamine infusions at our institution. Data examined associations between ketamine-related ADEs and various clinical characteristics including chronic pain, depression, or psychiatric disorder, patient physical characteristics, chronic opioid use, perioperative opioid use, dose and duration of ketamine infusions, pain scores, and perioperative medications such as serotonergic agents, central nervous system (CNS) depressants, and analgesics.Results: Overall incidence of ketamine-related ADEs was 29.5% and the incidence of psychomimetic effects was 14.8%. We observed that patients with a history of depression have a lower incidence of ketamine-related ADEs compared to patients without a history of depression (10.3% vs 37.3%; p value = 0.007).Conclusion: Patients with depression were found to have a statistically significant reduction in the incidence of ketamine-related ADEs. We found no statistically significant positive associations between ketamine-related ADEs and other clinical factors such as a history of chronic pain, psychiatric disease, patient physical characteristics, perioperative opioid use, dose of ketamine infusion, or co-administration of other CNS depressants.Keywords: ketamine, pain, depression, adverse, drug-event

Background: Patch testing for multiple cross-reactive allergens for allergic contact dermatitis (ACD) may not be necessary because of copositivity., Objectives: We evaluated the formaldehyde group allergens to determine the optimal, most cost-effective allergens to test., Methods: A retrospective analysis of Mayo Clinic (1997-2022) examined the well-established copositive formaldehyde group: formaldehyde, quaternium 15, hexahydro-1,3,5-tris(2-hydroxyethyl)triazine, diazolidinyl urea, imidazolidinyl urea, toluenesulphonamide formaldehyde resin, DMDM hydantoin, and ethyleneurea melamine formaldehyde mix. Patch Optimization Platform identified which single formaldehyde-related allergen optimally captures patients with clinically relevant ACD. Next, Patch Optimization Platform determined the optimal additional 1, 2, 3, etc. allergens. Cost per patch test was $5.19 (Medicare 2022)., Results: A total of 9832 patients were tested for all listed allergens, with 830 having positive patch test results. Patch Optimization Platform determined that quaternium 15 alone captures 53% of patients with ACD to the formaldehyde group; adding the optimal second allergen (formaldehyde 1%) captures 78%; the optimal 5 top allergens capture >94% of patients. The incremental cost per additional diagnosis increased up to 44-fold as the number of allergens tested increased., Limitations: Data are from a single institution, and the cost per test was fixed according to Medicare Part B in 2022., Conclusions: For diagnosing ACD, we recommend considering an optimized allergen selection algorithm., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Context: Humans with obesity and insulin resistance exhibit lipid accumulation in skeletal muscle, but the underlying biological mechanisms responsible for the accumulation of lipid in the muscle of these individuals remain unknown., Objective: We investigated how plasma insulin modulates the extraction of circulating triglycerides (TGs) and non-esterified fatty acids (NEFAs) from ingested and endogenous origin in the muscle of lean, insulin-sensitive humans (Lean-IS) and contrasted these responses to those in humans with obesity and insulin resistance (Obese-IR)., Methods: The studies were performed in a postprandial state associated with steady-state plasma TG concentrations. The arterio-venous blood sampling technique was employed to determine the extraction of circulating lipids across the forearm muscle before and after insulin infusion. We distinguished kinetics of TGs and NEFAs from ingested origin from those from endogenous origin across muscle by incorporating stable isotope-labeled triolein in the ingested fat., Results: Insulin infusion rapidly suppressed the extraction of plasma TGs from endogenous, but not ingested, origin in the muscle of the Lean-IS, but this response was absent in the muscle of the Obese-IR. Furthermore, in the muscle of the Lean-IS, insulin infusion decreased the extraction of circulating NEFAs from both ingested and endogenous origin; however, this response was absent for NEFAs from ingested origin in the muscle of the Obese-IR subjects., Conclusions: Partitioning of circulating lipids away from the skeletal muscle when plasma insulin increases during the postprandial period is impaired in humans with obesity and insulin resistance., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

In the Spring of 2020, the United States of America (USA) deployed COVID-19 convalescent plasma (CCP) to treat hospitalized patients. Over 500,000 patients were treated with CCP during the first year of the pandemic. In this study, we estimated the number of actual inpatient lives saved by CCP treatment in the United States of America based on CCP weekly use, weekly national mortality data, and CCP mortality reduction data from meta-analyses of randomized controlled trials and real-world data. We also estimate the potential number of lives saved if CCP had been deployed for 100% of hospitalized patients or used in 15 to 75% of outpatients. Depending on the assumptions modeled in stratified analyses, we estimated that CCP saved between 16,476 and 66,296 lives. The CCP ideal use might have saved as many as 234,869 lives and prevented 1,136,133 hospitalizations. CCP deployment was a successful strategy for ameliorating the impact of the COVID-19 pandemic in the USA. This experience has important implications for convalescent plasma use in future infectious disease emergencies., Competing Interests: Competing interests statement:Klassen S.A., Senefeld J.W., Johnson P.W., Carter R.E., Wiggins C.C., Shoham S., Henderson J.P., Pirofski L.A., Wright R.S., Paneth N.S., Casadevall A., and Joyner M.J. and reviewers Musser J. and Hartmann W.R. were co-authors in a review/position paper dealing with the use of CCP published in 2021.

Purpose: The optimal approach for partial breast irradiation (PBI) is unknown. We investigated a novel de-intensified 3-fraction PBI regimen for photons, protons, and brachytherapy., Methods and Materials: A multicenter nonrandomized controlled trial with the primary outcome of adverse cosmesis at 3 years versus before PBI. Eligibility criteria were age ≥50 years treated with breast-conserving surgery for node-negative estrogen receptor-positive (ER+) invasive breast cancer or any ductal carcinoma in situ (DCIS) measuring ≤2.5 cm. Photon and proton PBI were prescribed 21.9 Gy (relative biological effectiveness) and brachytherapy 21 Gy in 3 fractions. Radiation therapy technique and adjuvant endocrine therapy were selected at physician and patient discretion., Results: Between June 17, 2015, and July 13, 2017, 161 eligible patients were treated with photons (56), protons (49), or brachytherapy (56). Median patient age was 66.8 years. One hundred twenty-six (78.3%) had invasive breast cancer (all ER+) and 35 (21.7%) had DCIS (88.6% ER+). Fifty-four percent of patients with invasive breast cancer and 25.8% of patients with ER+ DCIS initiated and adhered to the prescribed endocrine therapy. The proportion of patients with adverse cosmesis (by trained nurse assessment) was 14.5% at baseline and 2.3% at 3 years (difference, -12.2%; 95% CI, -100% to -6.4%). Adverse cosmesis at the last follow-up, with a median follow-up of 5 years, was 5.7% by nurse assessment, 5.6% by panel assessment of digital photographs, and 5.2% by patient self-report. There were no observed clinically meaningful changes in other patient-reported outcomes, and just 2 grade 2 or higher adverse events, both grade 2, in the brachytherapy cohort. Five-year local recurrence-free survival and progression-free survival were 98.0% and 95.5%, respectively. There were no local recurrences among 60 patients with invasive breast cancer and Ki67 ≤13.25%., Conclusions: Deintensified 3-day PBI provided favorable disease control, tolerability, and cosmetic outcomes, meeting the prespecified criteria for acceptability. This approach is an attractive option for patients with small node-negative ER+ breast cancer and DCIS., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: Measurable residual disease (MRD) refers to the presence of disease at low levels not detected by conventional pathologic analysis. The association of MRD status as a surrogate end point of clinical outcome in chronic lymphocytic leukemia (CLL) has not been established in the era of targeted agents. Assessing the association of MRD with progression-free survival (PFS) may improve its role as a surrogate marker and allow its use to accelerate drug development., Objective: To assess the association between MRD and PFS in CLL using data from prospective clinical trials that studied targeted agents or obinutuzumab-based treatment., Data Sources: Clinical studies on CLL were identified via searches of PubMed, Embase, Scopus, and Web of Science from inception through July 31, 2023., Study Selection: Prospective, single-arm, and randomized clinical trials that assessed targeted agents or obinutuzumab-based treatment and reported PFS by MRD status were included. Studies with insufficient description of MRD information were excluded., Data Extraction and Synthesis: Study sample size, median patient age, median follow-up time, line of treatment, MRD detection method and time points, and survival outcomes were extracted., Main Outcomes and Measures: Analyses of survival probabilities and hazard ratios (HRs) were conducted for PFS according to MRD status. Meta-analyses were performed using a random-effects model., Results: A total of 11 prospective clinical trials (9 randomized and 2 nonrandomized) including 2765 patients were analyzed. Achieving undetectable MRD (uMRD) at 0.01% was associated with an HR of 0.28 (95% CI, 0.20-0.39; P < .001) for PFS. Median PFS was not reached in both groups (uMRD vs MRD), but the estimated 24-month PFS was better in the uMRD group (91.9% [95% CI, 88.8%-95.2%] vs 75.3% [95% CI, 64.7%-87.6%]; P < .001). The association of uMRD with PFS was observed in subgroup analyses in the first-line treatment setting (HR, 0.24; 95% CI, 0.18-0.33), relapsed or refractory disease setting (HR, 0.34; 95% CI, 0.16-0.71), and trials using time-limited therapy (HR, 0.28; 95% CI, 0.19-0.40)., Conclusions and Relevance: The findings of this systematic review and meta-analysis suggest that assessing MRD status as an end point in clinical trials and as a surrogate of PFS may improve trial efficiency and potentially allow for accelerated drug registration.

Tools used for the identification, evaluation, and monitoring of concussion have not been sufficiently studied in youth or real-world settings. Normative and reliability data on sideline concussion assessment measures in the youth athlete population is needed. Pre-season normative data for 515 athletes (93.5% male) aged 5 to 16 on the Standardized Assessment of Concussion (SAC/SAC-Child), modified Balance Errors Scoring System (mBESS), Timed Tandem Gait (TTG), and the King-Devick Test (KDT) are provided. A total of 212 non-injured athletes repeated the measures post-season to assess test-retest reliability. Mean performance on the SAC-C, mBESS, TTG, and KDT tended to improve with age. KDT was the only measure that demonstrated good to excellent stability across age ranges (ICC = 0.758 to 0.941). Concentration was the only SAC/SAC-C subtest to demonstrate moderate test-retest stability (ICC = 0.503 to 0.706). TTG demonstrated moderate to good (ICC = 0.666 to 0.811) reliability. mBESS demonstrated poor to moderate reliability (ICC = -0.309 to 0.651). Commonly used measures of concussion vary regarding test-retest reliability in youth. The data support the use of at least annual sport concussion baseline assessments in the pediatric population to account for the evolution in performance as the child ages. Understanding the variation in the stability and the evolution of baseline performance will enable improved identification of possible injury.

Objective: To examine the association of COVID-19 convalescent plasma transfusion with mortality and the differences between subgroups in hospitalized patients with COVID-19., Patients and Methods: On October 26, 2022, a systematic search was performed for clinical studies of COVID-19 convalescent plasma in the literature from January 1, 2020, to October 26, 2022. Randomized clinical trials and matched cohort studies investigating COVID-19 convalescent plasma transfusion compared with standard of care treatment or placebo among hospitalized patients with confirmed COVID-19 were included. The electronic search yielded 3841 unique records, of which 744 were considered for full-text screening. The selection process was performed independently by a panel of 5 reviewers. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data were extracted by 5 independent reviewers in duplicate and pooled using an inverse-variance random effects model. The prespecified end point was all-cause mortality during hospitalization., Results: Thirty-nine randomized clinical trials enrolling 21,529 participants and 70 matched cohort studies enrolling 50,160 participants were included in the systematic review. Separate meta-analyses reported that transfusion of COVID-19 convalescent plasma was associated with a decrease in mortality compared with the control cohort for both randomized clinical trials (odds ratio [OR], 0.87; 95% CI, 0.76-1.00) and matched cohort studies (OR, 0.76; 95% CI, 0.66-0.88). The meta-analysis of subgroups revealed 2 important findings. First, treatment with convalescent plasma containing high antibody levels was associated with a decrease in mortality compared with convalescent plasma containing low antibody levels (OR, 0.85; 95% CI, 0.73 to 0.99). Second, earlier treatment with COVID-19 convalescent plasma was associated with a decrease in mortality compared with the later treatment cohort (OR, 0.63; 95% CI, 0.48 to 0.82)., Conclusion: During COVID-19 convalescent plasma use was associated with a 13% reduced risk of mortality, implying a mortality benefit for hospitalized patients with COVID-19, particularly those treated with convalescent plasma containing high antibody levels treated earlier in the disease course., Competing Interests: Drs Senefeld, Carter, Joyner, Fairweather, Bruno, and Wright reported being investigators in the US Expanded Access Program of COVID-19 convalescent plasma. Drs Paneth, Casadevall, and Joyner reported serving as leadership for the COVID-19 Convalescent Plasma Project outside the submitted work., (© 2023 The Authors.)

Rheumatology research often involves correlated and clustered data. A common error when analyzing these data occurs when instead we treat these data as independent observations. This can lead to incorrect statistical inference. The data used are a subset of the 2017 study from Raheel et al consisting of 633 patients with rheumatoid arthritis (RA) between 1988 and 2007. RA flare and the number of swollen joints served as our binary and continuous outcomes, respectively. Generalized linear models (GLM) were fitted for each, while adjusting for rheumatoid factor (RF) positivity and sex. Additionally, a generalized linear mixed model with a random intercept and a generalized estimating equation were used to model RA flare and the number of swollen joints, respectively, to take additional correlation into account. The GLM's β coefficients and their 95% confidence intervals (CIs) are then compared to their mixed-effects equivalents. The β coefficients compared between methodologies are very similar. However, their standard errors increase when correlation is accounted for. As a result, if the additional correlations are not considered, the standard error can be underestimated. This results in an overestimated effect size, narrower CIs, increased type I error, and a smaller P value, thus potentially producing misleading results. It is important to model the additional correlation that occurs in correlated data., (Copyright © 2023 by the Journal of Rheumatology.)

Background: Food-specific immunoglobulin G4 (FS-IgG4) is associated with eosinophilic esophagitis (EoE); however, it is not clear whether production is limited to the esophagus., Aims: To assess FS-IgG4 levels in the upper gastrointestinal tract and plasma and compare these with endoscopic disease severity, tissue eosinophil counts, and patient-reported symptoms., Methods: We examined prospectively banked plasma, throat swabs, and upper gastrointestinal biopsies (esophagus, gastric antrum, and duodenum) from control (n = 15), active EoE (n = 24), and inactive EoE (n = 8) subjects undergoing upper endoscopy. Patient-reported symptoms were assessed using the EoE symptom activity index (EEsAI). Endoscopic findings were evaluated using the EoE endoscopic reference score (EREFS). Peak eosinophils per high-power field (eos/hpf) were assessed from esophageal biopsies. Biopsy homogenates and throat swabs were normalized for protein content and assessed for FS-IgG4 to milk, wheat, and egg., Results: Median FS-IgG4 for milk and wheat was significantly increased in the plasma, throat swabs, esophagus, stomach, and duodenum of active EoE subjects compared to controls. No significant differences for milk- or wheat-IgG4 were observed between active and inactive EoE subjects. Among the gastrointestinal sites sampled, FS-IgG4 levels were highest in the esophagus. Esophageal FS-IgG4 for all foods correlated significantly across all sites sampled (r ≥ 0.59, p < 0.05). Among subjects with EoE, esophageal FS-IgG4 correlated significantly with peak eos/hpf (milk and wheat) and total EREFS (milk). EEsAI scores and esophageal FS-IgG4 levels did not correlate., Conclusions: Milk and wheat FS-IgG4 levels are elevated in plasma and throughout the upper gastrointestinal tract in EoE subjects and correlate with endoscopic findings and esophageal eosinophilia., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Atrioventricular block requiring permanent pacemaker (PPM) implantation is an important complication of transcatheter aortic valve replacement (TAVR). Application of machine learning could potentially be used to predict pre-procedural risk for PPM., Aim: To apply machine learning to be used to predict pre-procedural risk for PPM., Methods: A retrospective study of 1200 patients who underwent TAVR (January 2014-December 2017) was performed. 964 patients without prior PPM were included for a 30-d analysis and 657 patients without PPM requirement through 30 d were included for a 1-year analysis. After the exclusion of variables with near-zero variance or ≥ 50% missing data, 167 variables were included in the random forest gradient boosting algorithm (GBM) optimized using 5-fold cross-validations repeated 10 times. The receiver operator curve (ROC) for the GBM model and PPM risk score models were calculated to predict the risk of PPM at 30 d and 1 year., Results: Of 964 patients included in the 30-d analysis without prior PPM, 19.6% required PPM post-TAVR. The mean age of patients was 80.9 ± 8.7 years. 42.1 % were female. Of 657 patients included in the 1-year analysis, the mean age of the patients was 80.7 ± 8.2. Of those, 42.6% of patients were female and 26.7% required PPM at 1-year post-TAVR. The area under ROC to predict 30-d and 1-year risk of PPM for the GBM model (0.66 and 0.72) was superior to that of the PPM risk score (0.55 and 0.54) with a P value < 0.001., Conclusion: The GBM model has good discrimination and calibration in identifying patients at high risk of PPM post-TAVR., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Purpose: Patient-reported outcomes provide quality of life (QOL) data during and after radiation. When pediatric patients are unable to complete patient-reported outcomes, it is unknown whether caregiver responses are an accurate surrogate. We assessed whether caregiver scores for the Pediatric Quality of Life Inventory (PedsQL) Core and Brain Tumor Module questionnaires can substitute for missing child scores., Methods and Materials: From 2016 to 2018, pediatric patients treated with radiation were followed in a prospective, institutional registry. Child and caregiver Core and Tumor PedsQL surveys were obtained at pretreatment, end of treatment, and in regular follow-up. The differences between the 2 scores at each time point were quantified using a linear mixed-model and the level of agreement was estimated with intraclass correlation coefficient (ICC). An ICC 95% confidence interval (CI) lower limit exceeding 0.75 was considered an acceptable threshold for using caregiver scores as imputed values for missing child scores., Results: Ninety-one children completed 403 surveys. Caregivers underestimated QOL scores at baseline, but not at end of treatment or any follow-up time. The PedsQL Core total score had an ICC of 0.88 (95% CI, 0.81-0.92), and the emotional, physical, school, and social function subdomain scores were 0.81 (0.72-0.88), 0.72 (0.58-0.82), 0.79 (0.68-0.86), and 0.75 (0.62-0.83), respectively. The tumor total score ICC was 0.91 (0.85, 0.94), and each of the subdomains (cognitive problems, communication, movement and balance, nausea, pain and hurt, perceived physical appearance, procedural anxiety, treatment anxiety, and worry) had ICC lower bound 95% CI ≥0.75 except for communication (0.83, 0.74-0.89). Bland-Altman analysis demonstrated no visual change in discrepancy between child and caregiver estimates as overall QOL improved., Conclusions: Agreement between child- and caregiver-reported QOL was generally strong in the acute period after radiation, implying that caregiver scores may be imputed for child scores in future protocols and analyses of pediatric QOL., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Competing Interests: Conflicts of interest None disclosed.

The Banff classification scheme provides a framework for interpreting transplant kidney biopsies and has undergone various updates in the past 2 decades especially related to antibody-mediated rejection. The clinical significance of early glomerulitis seen within 4 mo on protocol biopsies has received limited attention. We hypothesized that early glomerulitis seen on protocol biopsies will lead to significant adverse outcomes as assessed by histopathology and allograft outcome., Methods: A single-center retrospective study of a cohort of patients who underwent protocol biopsies within 4 mo after transplantation with timely follow-up protocol biopsies were assessed. Patients with recurrent glomerulonephritis were excluded., Results: We calculated glomerulitis (g) scores for 2212 biopsy specimens and identified 186 patients with glomerulitis (g > 0) and 2026 patients without glomerulitis (g = 0). The progression to chronic transplant glomerulopathy at 1 and 2 y was higher in patients with g > 0 as compared with g = 0 (year 1, 10.7% versus 2.3% [ P  < 0.001]' respectively; year 2, 17.2% versus 4.3% [ P  < 0.001], respectively) with no difference in other chronic lesions. The death-censored graft failure rate was higher in patients with g > 0 as compared with g = 0 (hazard ratio, 1.68 [95% CI, 1.07-2.65]; P  = 0.02). We did not find any difference in outcomes in glomerulitis group based on donor-specific antibody., Conclusion: Our findings suggest that early glomerulitis (seen within 4 mo after transplantation) may lead to clinically significant long-term changes and thus could be a target for early intervention therapies., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2022 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Background: Understanding the accuracy of a woman's perceived breast cancer risk can enhance shared decision-making about breast cancer screening through provider and patient discussion. We aim to report and compare women's perceived lifetime breast cancer risk to calculated lifetime breast cancer risk. Methods: Women presenting to Mayo Clinic in Arizona and Minnesota in July 2016 completed a survey assessing their perceived breast cancer risk. Lifetime Gail risk scores were calculated from questions pertaining to health history and were then compared with perceived breast cancer risk. Results: A total of 550 predominantly white, married, and well-educated (≥college) women completed surveys. Using lifetime Gail risk scores, 5.6% were classified as high risk (>20% lifetime risk), 7.7% were classified as intermediate risk (15%-20%), and 86.6% were classified as average risk (<15%). Of the 27 women who were classified as high risk, 18 (66.7%) underestimated their risk and of the 37 women who were intermediate risk, 12 (32.4%) underestimated risk. Women more likely to underestimate their risk had a reported history of an abnormal mammogram and at least one or more relative with a history of breast cancer. Surveyed women tended to overestimate risk 4.3 (130/30) times as often as they underestimated risk. Conclusion: In a group of predominantly white, educated, and married cohort of women, there was a large portion of women in the elevated risk groups who underestimated risk. Specific aspects of medical history were associated with underestimation including a history of abnormal mammogram and family history of breast cancer. Overall, in our sample, more women overestimated than underestimated risk.

Context: Enhanced Recovery After Surgery (ERAS) is a multimodal protocol aimed to improve quality of postoperative recovery, minimize complications, and optimize overall self-regulation. Preoperative gabapentin decreases postoperative pain but can be associated with prolonged postoperative somnolence and respiratory depression risk. Although it is known that gabapentin affects the postoperative course, it is unclear if the timing of preoperative administration affects this finding., Objectives: This study aims to assess the optimal preoperative timing for gabapentin administration in patients undergoing gynecologic surgery to minimize postoperative somnolence risk., Methods: A retrospective cohort study evaluated patients who underwent major gynecologic surgery and received preoperative gabapentin. Patients were grouped based on timing from gabapentin administration to surgical incision (<4 h group vs. ≥4 h group). Preoperative, intraoperative, and postoperative data were abstracted and compared. Univariate associations between the timing of gabapentin administration and the patient and surgical characteristics and outcomes were tested utilizing two-sample equal-variance t-tests, linear model ANOVA, or Fisher's exact tests. Associations between the timing of gabapentin administration and the time until the Richmond Agitation Sedation Scale (RASS) score of 0 were modeled utilizing linear regression, adjusted for age, initial postoperative anesthesia care unit (PACU), RASS score, and postoperative narcotics., Results: Each group contained 127 patients. Demographics were similar except for age (<4 h group mean=44.2 years; ≥4 h group mean=40.5 years; p=0.021), chronic pain (<4 h group=17.6%; ≥4 h group=43.3%; p<0.001), and surgical indication (<4 h group=pelvic pain [29.1%]; ≥4 h group=pelvic pain [51.2%]; p=0.007). The <4 h group had a similar postoperative narcotic administration (<4 h group mean morphine milligram equivalents [MME]=3.667; ≥4 h group mean MME=4.833; p=0.185). The minutes from surgical closure until the patient received a RASS score of 0 and initial PACU pain score (Visual Analogue Scale [VAS]) were similar. The initial PACU oxygen administration volume, hours from surgical closure until the patient transitioned to room air, and initial PACU respiratory rate were similar. The PACU duration, admission secondary to somnolence, and initial PACU Glasgow Coma Scale (GCS) score showed no difference. Postoperative nausea/vomiting was decreased in the ≥4 h group (<4 h group=24.4%; ≥4 h group=13.4%; p-value=0.036), and urinary retention (<4 h group=14.2%; ≥4 h group=5.5%; p-value=0.033) was decreased in the ≥4 h group., Conclusions: The timing of gabapentin administration less than or more than 4 h preoperatively in patients ≥ 18 years does not significantly affect postoperative somnolence or respiratory depression. Further, it does not have a significant effect on GCS scores or VAS scores., (© 2022 Summer Ghaith et al., published by De Gruyter, Berlin/Boston.)

Background: The United States (US) Expanded Access Program (EAP) to coronavirus disease 2019 (COVID-19) convalescent plasma was initiated in response to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. While randomized clinical trials were in various stages of development and enrollment, there was an urgent need for widespread access to potential therapeutic agents. The objective of this study is to report on the demographic, geographical, and chronological characteristics of patients in the EAP, and key safety metrics following transfusion of COVID-19 convalescent plasma., Methods and Findings: Mayo Clinic served as the central institutional review board for all participating facilities, and any US physician could participate as a local physician-principal investigator. Eligible patients were hospitalized, were aged 18 years or older, and had-or were at risk of progression to-severe or life-threatening COVID-19; eligible patients were enrolled through the EAP central website. Blood collection facilities rapidly implemented programs to collect convalescent plasma for hospitalized patients with COVID-19. Demographic and clinical characteristics of all enrolled patients in the EAP were summarized. Temporal patterns in access to COVID-19 convalescent plasma were investigated by comparing daily and weekly changes in EAP enrollment in response to changes in infection rate at the state level. Geographical analyses on access to convalescent plasma included assessing EAP enrollment in all national hospital referral regions, as well as assessing enrollment in metropolitan areas and less populated areas that did not have access to COVID-19 clinical trials. From April 3 to August 23, 2020, 105,717 hospitalized patients with severe or life-threatening COVID-19 were enrolled in the EAP. The majority of patients were 60 years of age or older (57.8%), were male (58.4%), and had overweight or obesity (83.8%). There was substantial inclusion of minorities and underserved populations: 46.4% of patients were of a race other than white, and 37.2% of patients were of Hispanic ethnicity. Chronologically and geographically, increases in the number of both enrollments and transfusions in the EAP closely followed confirmed infections across all 50 states. Nearly all national hospital referral regions enrolled and transfused patients in the EAP, including both in metropolitan and in less populated areas. The incidence of serious adverse events was objectively low (<1%), and the overall crude 30-day mortality rate was 25.2% (95% CI, 25.0% to 25.5%). This registry study was limited by the observational and pragmatic study design that did not include a control or comparator group; thus, the data should not be used to infer definitive treatment effects., Conclusions: These results suggest that the EAP provided widespread access to COVID-19 convalescent plasma in all 50 states, including for underserved racial and ethnic minority populations. The study design of the EAP may serve as a model for future efforts when broad access to a treatment is needed in response to an emerging infectious disease., Trial Registration: ClinicalTrials.gov NCT#: NCT04338360., Competing Interests: The authors have declared that no competing interests exist.

Objective: Menopausal symptoms may differ by geography and ethnicity, but the impact of socioeconomic factors is less clear. The purpose of this study was to compare menopausal symptoms in women from areas of Arizona with different socioeconomic resources., Study Design: Women aged 40-65 years in two cohorts were surveyed: (1) Phoenix women attending either a clinic for patients who are uninsured or a clinic for people experiencing homelessness; and (2) Scottsdale women living in zip codes with higher average income and neighborhood advantage (surveyed by mail). Surveys included the Greene Climacteric Scale (GCS) and demographic questions., Main Outcome Measures: GCS score by domain and subdomain, corrected for age, race, menopause stage and menopausal hormone therapy (HT)., Results: Phoenix participants (N = 104) were 51.2 years old (SD 6.45), Hispanic (54.4%), White (28.2%) or African American (8.7%), and uninsured (53.0%). Scottsdale participants (N = 151) were 52.6 years old (SD 5.52), mostly White (94.7%) and insured (100%). Three percent of Phoenix women were on HT vs. 23.3% in Scottsdale (p < 0.001). Multivariate analysis revealed higher total GCS scores in the Phoenix vs. Scottsdale cohort (39.13 vs 30.14, p < 0.001), which was also seen in the psychological and somatic domains, as well as the anxiety and depression subdomains. No statistically significant differences were seen in the vasomotor or sexual dysfunction domains., Conclusion: In a group of women living in Arizona from distinct socioeconomic areas, significant differences were demonstrated in menopausal symptom bother specifically with higher psychological and somatic symptoms in women who were uninsured or experiencing homelessness independent of age, race, menopause stage and HT use. Future studies controlling for co-morbidities associated with lower socioeconomic status such as depression would provide further insight into this population of midlife women., (Copyright © 2021. Published by Elsevier B.V.)

Background: Diagnosis of non-esophageal eosinophilic gastrointestinal disorders requires quantification of tissue eosinophils. Our objective was to evaluate eosinophil peroxidase (EPX) immunohistochemistry (IHC) as a method for histologic diagnosis of eosinophilic gastritis (EG) and eosinophilic duodenitis (EoD)., Methods: We performed a retrospective analysis of biopsies from pediatric EG/EoD cases and controls. Subjects with EG or EoD had ≥30 eosinophils per high power field (eos/hpf) in ≥5 hpf in the stomach and/or ≥3 hpf in the duodenum, respectively. Controls had no histopathologic diagnosis recorded. Tissue eosinophil counts were assessed by hematoxylin & eosin stains. EPX stains were assessed using a unique histopathologic scoring system. Slides were digitized and EPX+ staining area/mm 2 was quantified by image analysis., Results: Twenty-six EG/EoD cases and 40 controls were analyzed. EPX scores and EPX/mm 2 levels were markedly elevated in EG/EoD (p ≤ 0.0001). Eosinophil density (eos/mm 2 ) correlated strongly with EPX scores and EPX/mm 2 levels in the stomach (r ≥ 0.77) and moderately with EPX scores and EPX/mm 2 levels in the duodenum (r ≥ 0.52); (p < 0.0001). EPX quantification identified EG/EoD subjects with high diagnostic accuracy (EPX score: AUC = 1 for EG and EoD; EPX/mm 2 : AUC = 0.98 (95%CI 0.96-1) for EG, AUC = 0.91 (95%CI 0.81-1) for EoD)., Conclusion: EPX-based assessment of eosinophilic inflammation may facilitate automated histologic diagnosis.

Background: An essential component of patient-centered, individualized medicine is considering how sex and gender affect mechanisms of health and disease., Objectives: To assess medical students' current knowledge of sex and gender specific health (SGSH) concepts compared to results from the same survey in 2012 to better inform development of curricular materials for medical education., Methods: A previously designed survey tool, which assessed current knowledge of sex and gender-based medicine of medical students, was emailed to all Mayo Clinic Alix School of Medicine (MCASOM) students on Minnesota, Arizona, and Florida campuses in 2020. Descriptive and qualitative thematic results were compared to the same survey administered in 2012 to students enrolled in MCASOM. Changes in the inclusion of SGSH topics were assessed over the eight years., Results: One hundred and one of 365 (27.7% response rate) surveys were returned with 2:1 female to male respondents with representation from all 4 years. The definitions of the terms "sex" and "gender" were correctly identified by most respondents (93.1%). However, only 36% (12/33) of questions related to other medical knowledge on SGSH topics had more than a 50% correct response rate. More than half of the students reported that SGSH topics were included in Gynecology, Cardiology, Pediatrics, and Immunology. SGSH topics were reported as not being routinely covered in Neurology and Nephrology, although more students said they were in 2020 then 2012. Sixty-two percent of students favored increasing SGSH in the current curriculum., Conclusions: Medical students appear to understand the definition of and importance of SGSH in education. While some improvements in coverage by subject matter and topic area appear to have occurred as reported by medical students, opportunity remains to more fully integrate SGSH concepts in medical school curricula., (© 2021. The Author(s).)

Successful therapeutics and vaccines for coronavirus disease 2019 (COVID-19) have harnessed the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Evidence that SARS-CoV-2 exists as locally evolving variants suggests that immunological differences may impact the effectiveness of antibody-based treatments such as convalescent plasma and vaccines. Considering that near-sourced convalescent plasma likely reflects the antigenic composition of local viral strains, we hypothesize that convalescent plasma has a higher efficacy, as defined by death within 30 days of transfusion, when the convalescent plasma donor and treated patient were in close geographic proximity. Results of a series of modeling techniques applied to approximately 28,000 patients from the Expanded Access to Convalescent Plasma program (ClinicalTrials.gov number: NCT04338360) support this hypothesis. This work has implications for the interpretation of clinical studies, the ability to develop effective COVID-19 treatments, and, potentially, for the effectiveness of COVID-19 vaccines as additional locally-evolving variants continue to emerge., (© 2021. The Author(s).)

Introduction: Obesity is a common comorbidity seen in the perioperative setting and is associated with many diseases including cardiovascular disease and obstructive sleep apnea. Laparoscopic Roux-en-Y gastric bypass is the gold standard surgical treatment for patients whose weight is refractory to diet and exercise. Caring for these patients perioperatively presents unique challenges to anesthesiologists and is associated with an increased risk of adverse respiratory events. In our study, we hypothesize that a low-dose perioperative ketamine infusion will reduce opioid consumption and improve analgesia when compared to standard therapy., Methods: This is a single-center, prospective randomized controlled study enrolling 35 patients in total. Patients were randomized equally into the ketamine and control group. Preop, intraop, and postop management regimens were standardized. The ketamine group received a 0.3 mg/kg ideal body weight ketamine bolus after induction followed by a 0.2 mg/kg/hr ketamine infusion continued into the postop setting for up to 24 hours. Data collected included total perioperative opioids used converted to oral morphine equivalents (ME), pain scores, side effects, hospital length of stay, and patient satisfaction captured via postoperative questionnaires., Results: The use of perioperative opioid consumption was significantly lower in the ketamine group when compared with the control group (179.9 ME versus 248.7 ME, P =0.03). There was no statistically significant difference in pain scores or hospital length of stay postoperatively between the two groups. There were also no reported adverse respiratory events, prolonged sedation, agitation, or other side effects reported in either group. The patient satisfaction questionnaires showed a significant difference with the ketamine group reporting lower maximum pain scores, a decrease in how pain limited activities of daily living once discharged, and increased hospital pain management satisfaction scores., Conclusions: Perioperative low-dose ketamine infusions significantly reduced opioid consumption in morbidly obese patients undergoing laparoscopic gastric bypass surgery., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Mitchell T. Seman et al.)

Objective: To evaluate menopausal symptoms and sexual problems in Hispanic and non-Hispanic women in two Southwest areas., Methods: An anonymous survey including the Green Climacteric Scale (GCS), Female Sexual Function Index (FSFI), and demographics was distributed to English and Spanish-speaking women age 40 to 60 in Scottsdale, Arizona, and West Texas. FSFI for sexually active women and GCS scores for the Hispanic and non-Hispanic women in Texas were analyzed with multivariable analysis and compared between Texas and Arizona for Non-Hispanic participants., Results: Predominantly non-Hispanic women (70%), average age 51.5 (SD = 7.25) completed questionnaires (199 West Texas, 163 Scottsdale). A majority of sexually active women (88%) were found to be at risk of sexual dysfunction. Within the Texas cohort, GCS score was estimated to be 3.49 points lower (less symptoms) in Hispanic versus non-Hispanic participants [95% CI -6.58 to -0.40, P = 0.03], and FSFI score was estimated to be 2.31 points lower (more symptoms) in Hispanic versus non-Hispanic participants [95% CI -4.49 to -0.14, P = 0.04]. Among non-Hispanic women, GCS scores were lower (less symptoms) in Texas versus Arizona by 10.25 points [95% CI -14.83 to -5.66, P < 0.01], while FSFI scores were higher overall (less symptoms) in Texas by 3.65 points [95% CI 0.53-6.77), P = 0.02]. All FSFI and GCS scores were adjusted for multiple variables., Conclusions: In a group of menopausal women from the Southwest, most reported symptoms were consistent with FSD, and the degree of sexual problems appeared to be greater in the Hispanic participants from Texas., Competing Interests: Financial disclosures/conflicts of interest: The authors have no conflicts of interest., (Copyright © 2021 by The North American Menopause Society.)

Approximately 5 to 15% of patients with pulmonary coccidioidomycosis subsequently develop pulmonary cavities. These cavities may resolve spontaneously over a number of years; however, some cavities never close, and a small proportion causes complications such as hemorrhage, pneumothorax or empyema. The impact of azole antifungal treatment on coccidioidal cavities has not been studied. Because azoles are a common treatment for symptomatic pulmonary coccidioidomycosis, we aimed to assess the impact of azole therapy on cavity closure. From January 1, 2004, through December 31, 2014, we retrospectively identified 313 patients with cavitary coccidioidomycosis and excluded 42 who had the cavity removed surgically, leaving 271 data sets available for study. Of the 271 patients, 221 (81.5%) received azole therapy during 5-year follow-up; 50 patients did not receive antifungal treatment. Among the 271 patients, cavities closed in 38 (14.0%). Statistical modeling showed that cavities were more likely to close in patients in the treated group than in the nontreated group (hazard ratio, 2.14 [95% CI: 1.45-5.66]). Cavities were less likely to close in active smokers than nonsmokers (11/41 [26.8%] vs 97/182 [53.3%]; P = 0.002) or in persons with than without diabetes (27/74 [36.5%] vs 81/149 [54.4%]; P = 0.01).We did not find an association between cavity size and closure. Our findings provide rationale for further study of treatment protocols in this subset of patients with coccidioidomycosis., Lay Summary: Coccidioidomycosis, known as valley fever, is a fungal infection that infrequently causes cavities to form in the lungs, which potentially results in long-term lung symptoms. We learned that cavities closed more often in persons who received antifungal drugs, but most cavities never closed completely., (© The Author(s) 2021. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Background: Currently, in the United States, there is an epidemic of opioid abuse. While this problem is well known to the public due to significant media and political attention, patients are poorly educated on the proper handling and disposal of unused opioids. Instead, the onus has fallen on the healthcare provider to minimize the number of opioids prescribed., Study Objective: To improve proper opioid disposal rates after gynecologic surgery by providing educational materials along with a disposal bag., Study Design: We performed a prospective study evaluating baseline understanding of medication disposal using a questionnaire given to the patients during their preoperative visit. Subsequently, patients were provided written information on proper disposal of their medications and an activated charcoal medication disposal bag. Study patients completed a survey about disposal of their unused opioids at their last post-operative visit. The success of education and proper disposal of opioid medications were evaluated., Results: Thirty-five patients, average age of 45 (range 20-77), were enrolled, and 31 patients successfully completed both surveys. The surgeries performed included hysterectomy 23 percent (n = 7), laparoscopic excision of endometriosis 32 percent (n = 10), laparoscopic ovarian cystectomy 23 percent (n = 7), prolapse repair 3 percent (n = 1), and midurethral sling procedures 19 percent (n = 6). Chronic pelvic pain was identified in 39 percent (n = 12) of our patient population. Prior to education, 52 percent (n = 16) of patients did not dispose of their opioids. Furthermore, 71 percent (n = 22) of patients stated they had never been educated by a medical provider regarding appropriate disposal. Nineteen percent (n = 6) confirmed they have used an opioid medication prescribed to someone else. Demographic data show 65 percent (n = 20) of these patients had completed a college degree or greater. After education and being given a reliable option for medication disposal with the Deterra® bag, 94 percent (n = 29) of patients properly disposed of their opioids after surgery, demonstrating a 45 percent (p < 0.001) increase in proper disposal. In our study alone, 491 tablets of 5mg oxycodone were properly disposed. The majority of patients, 77 percent (n = 24) used the drug disposal bag, and when queried, stated they would be willing to pay on average $7.70 (range 0-20) per bag. Without education and a simple option for disposal, 422 tablets prescribed may have been subject to inappropriate diversion., Conclusion: This study clearly shows that patient education, coupled with a reliable option for opioid disposal, is effective. We strongly encourage other surgical institutions to implement similar practices not only for our surgical patients' safety, but also for the tens of thousands of patients who died of opioid abuse in the last year.

Background: Convalescent plasma has been widely used to treat coronavirus disease 2019 (Covid-19) under the presumption that such plasma contains potentially therapeutic antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can be passively transferred to the plasma recipient. Whether convalescent plasma with high antibody levels rather than low antibody levels is associated with a lower risk of death is unknown., Methods: In a retrospective study based on a U.S. national registry, we determined the anti-SARS-CoV-2 IgG antibody levels in convalescent plasma used to treat hospitalized adults with Covid-19. The primary outcome was death within 30 days after plasma transfusion. Patients who were enrolled through July 4, 2020, and for whom data on anti-SARS-CoV-2 antibody levels in plasma transfusions and on 30-day mortality were available were included in the analysis., Results: Of the 3082 patients included in this analysis, death within 30 days after plasma transfusion occurred in 115 of 515 patients (22.3%) in the high-titer group, 549 of 2006 patients (27.4%) in the medium-titer group, and 166 of 561 patients (29.6%) in the low-titer group. The association of anti-SARS-CoV-2 antibody levels with the risk of death from Covid-19 was moderated by mechanical ventilation status. A lower risk of death within 30 days in the high-titer group than in the low-titer group was observed among patients who had not received mechanical ventilation before transfusion (relative risk, 0.66; 95% confidence interval [CI], 0.48 to 0.91), and no effect on the risk of death was observed among patients who had received mechanical ventilation (relative risk, 1.02; 95% CI, 0.78 to 1.32)., Conclusions: Among patients hospitalized with Covid-19 who were not receiving mechanical ventilation, transfusion of plasma with higher anti-SARS-CoV-2 IgG antibody levels was associated with a lower risk of death than transfusion of plasma with lower antibody levels. (Funded by the Department of Health and Human Services and others; ClinicalTrials.gov number, NCT04338360.)., (Copyright © 2021 Massachusetts Medical Society.)

Background: Little is known about menopausal symptoms in underserved women. Aim: To better understand self-reported menopausal symptoms in underserved and homeless women living in extreme heat during different seasons. Methods: A cross-sectional study, including the Greene Climacteric Scale (GCS), climate-related questions, and demographics was administered June to August of 2017 and December to February 2018 to women 40-65 years of age. Results: In 104 predominantly Hispanic (56%), uninsured (53%), menopausal (56%), and mid-aged (50 ± 9.5) women, 57% reported any bother, while 20% of these women reported "quite a bit" or "extreme" bother from hot flushes. The total GCS score was a mean of 41 ± 15.0; out of 63 indicating significant symptoms, the psychological and somatic clusters were highest. Women did not think temperature outside influenced their menopausal symptoms at either time point (69% in winter vs. 57% in summer, p  = 0.23). In multivariable analyses after adjusting for race, body mass index, and living situation neither season nor temperature was associated with self-reported hot flush bother. While one-third of women reported becoming ill from the heat, 90% of women reported not seeking care from a doctor for their illness. Conclusion: Menopausal, underserved, homeless women living in Arizona reported few vasomotor symptoms regardless of season, and endorsed psychological and somatic complaints. Socioeconomic factors may influence types of bothersome menopausal symptoms in this population of women., Competing Interests: No competing financial interests exist., (© Mahnoor Mukarram et al., 2021; Published by Mary Ann Liebert, Inc.)

Aim: We aimed to determine the impact of diabetes mellitus (DM) on survival of patients with neuroendocrine tumors (NETs) and of NETs on glycemic control., Patients & Methods: Patients with newly diagnosed NETs with/without DM were matched 1:1 by age, sex and diagnosis year (2005-2017), and survival compared (Kaplan-Meier and Cox proportional hazards). Mixed models compared hemoglobin A 1c (HbA 1c ) and glucose during the year after cancer diagnosis., Results: Three-year overall survival was 72% (95% CI: 60-86%) for DM patients versus 80% (95% CI: 70-92%) for non-DM patients (p = 0.82). Hazard ratio was 1.33 (95% CI: 0.56-3.16; p = 0.51); mean DM HbA 1c , 7.3%., Conclusion: DM did not adversely affect survival of patients with NET. NET and its treatment did not affect glycemic control., Competing Interests: Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript., (© 2021 Mayo Foundation for Medical Education and Research.)

Delirium in the hospitalized orthopaedic patient is associated with numerous negative outcomes. Assessing for the presence of delirium using an accurate and reliable tool is essential. However, the number of validated screening tools is limited. The purpose of this study was to validate and test the reliability of the Delirium Triage Screening and brief Confusion Assessment Method (DTS/bCAM) to screen for delirium in non-intensive care (ICU) orthopaedic and hematological patients. This was a prospective, observational study. Seventy-six delirium assessments were completed on 19 orthopaedic patients and 10 hematological patients. The clinical nurse performed the DTS/bCAM during every 12-hour shift. Within 2 hours of this assessment, a research investigator performed both the DTS/bCAM and the Confusion Assessment Method (CAM). Each patient had a maximum of three assessments by a research investigator. Interrater reliability for the clinical nurse and the researcher was measured through comparison of positive and negative DTS/bCAM results. Validity was measured by comparing the matched DTS/bCAM and CAM results, both performed by the researcher. The DTS/bCAM and CAM results had 100% agreement. Two patients (7%) screened positive for delirium. Sensitivity of the DTS/bCAM was 100% (95% CI [15.8-100]) and specificity was 100% (95% CI [95.1, 100]). There was 86% agreement (43/50) between the clinical nurse and the researcher for the DTS/bCAM. In adult orthopaedic and hematological patients not receiving intensive care, the DTS/bCAM may be a valid, reliable, and rapid screening tool for delirium., Competing Interests: Conflicts of Interest: None declared., (Copyright © 2021 by National Association of Orthopaedic Nurses.)

Aim: To evaluate associations between survival and glycemic control in age-matched patients with endometrial or ovarian cancer, with/without diabetes mellitus (DM)., Patients & Methods: Patients with newly diagnosed ovarian or endometrial cancer with and without DM were compared., Results: The study included 84 patients with ovarian cancer (28, DM); 96 with endometrial cancer (48 with, 48 without DM). DM patients did not have worse overall or progression-free survival than non-DM patients. Glycemic control was not associated with either cancer., Conclusion: There was no association between DM and survival for patients with uterine or ovarian cancer. In addition, there was no association between uterine and ovarian cancer and glycemic control. Additional studies to confirm these observations in larger populations are required., Competing Interests: Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants, patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript., (© 2020 Mayo Foundation for Medical Education and Research.)

Objective: We aimed to develop a risk prediction model using a machine learning to predict survival and graft failure (GF) 5 years after orthotopic heart transplant (OHT)., Methods: Using the International Society of Heart and Lung Transplant (ISHLT) registry data, we analyzed 15,236 patients who underwent OHT from January 2005 to December 2009. 342 variables were extracted and used to develop a risk prediction model utilizing a gradient-boosted machine (GBM) model to predict the risk of GF and mortality 5 years after hospital discharge. After excluding variables missing at least 50% of the observations and variables with near zero variance, 87 variables were included in the GBM model. Ten fold cross-validation repeated 5 times was used to estimate the model's external performance and optimize the hyperparameters simultaneously. Area under the receiver operator characteristic curve (AUC) for the GBM model was calculated for survival and GF 5 years post-OHT., Results: The median duration of follow-up was 5 years. The mortality and GF 5 years post-OHT were 27.3% (n = 4161) and 28.1% (n = 4276), respectively. The AUC to predict 5-year mortality and GF is 0.717 (95% CI 0.696-0.737) and 0.716 (95% CI 0.696-0.736), respectively. Length of stay, recipient and donor age, recipient and donor body mass index, and ischemic time had the highest relative influence in predicting 5-year mortality and graft failure., Conclusion: The GBM model has a good accuracy to predict 5-year mortality and graft failure post-OHT.

Objective: Endovascular aneurysm repair (EVAR) can result in high radiation dose to patients and operators. This prospective randomized study aimed to assess whether patient radiation dose sustained during EVAR could be decreased by predominantly using digital fluoroscopy (DF) vs the standard technique using digital subtraction angiography (DSA)., Methods: Between February 2011 and June 2017, patients with EVAR of infrarenal abdominal aortic aneurysms were prospectively enrolled and randomly assigned to a standard treatment DSA cohort or a DF cohort in which two or fewer DSA acquisitions were allowed for confirmatory imaging. Primary end points included dose-area product (DAP) and cumulative air kerma. Secondary end points included technical success and conversion to DSA standard treatment (if DF was inadequate for visualization)., Results: For all 43 patients enrolled (26 in the DF cohort, 17 in the DSA cohort), technical success was 100%. Of the 26 DF patients, 5 (19%) required conversion to the DSA cohort. In an intention-to-treat analysis, mean DAP was significantly lower in the DF cohort than in the DSA cohort (132 vs 174 Gy·cm 2 ; P = .04). When patients were separated by number of DSA acquisitions (two or fewer vs three or more), mean DAP decreased 41% (109 vs 185 Gy·cm 2 ; P = .005) and cumulative air kerma decreased 40% (578 vs 964 mGy; P = .004)., Conclusions: In most patients (81%), DF or limited DSA was adequate for visualization during EVAR. In both intention-to-treat DF and limited-DSA cohorts, mean DAP was significantly decreased. If image quality allows, a DF-only or limited-DSA approach to EVAR decreases radiation dose., (Copyright © 2020 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Aim: We examined the effect of diabetes on survival in patients with lymphoma and the effect of lymphoma on glycemic control., Patients & Methods: Patients with lymphoma with and without diabetes (2005-2016) were retrospectively identified and matched 1:1. Overall survival and progression-free survival were estimated by the Kaplan-Meier method. Hemoglobin A 1c (HbA 1c ) and glucose levels during the year after cancer diagnosis were compared by mixed models., Results: For patients with diabetes, mean HbA 1c during the year after lymphoma diagnosis was 6.7%. Estimated 5-year progression-free survival for patients with versus without diabetes was 63% (95% CI: 53-76%) versus 58% (95% CI: 46-71%) (p = 0.42)., Conclusion: Lymphoma and its treatment did not affect glycemic control. Diabetes did not decrease lymphoma-specific survival., Competing Interests: Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript., (© 2020 Mayo Foundation for Medical Education and Research.)

Aim: We examined the association between diabetes and survival in patients with acute and chronic myeloid leukemia and the association of leukemia with glycemic control., Patients & Methods: Patients with leukemia with and without diabetes (2007-2015) were retrospectively identified and matched 1:1 (n = 70 per group). Overall survival was estimated by the Kaplan-Meier method. Hemoglobin A 1c  and glucose levels the year after leukemia diagnosis were compared by mixed models., Results: Among 25 of 70 patients with diabetes, mean hemoglobin A 1c during the year after leukemia diagnosis was 6.8%. Kaplan-Meier-estimated 3-year survival was 46% for diabetes patients versus 45% for controls (p = 0.79)., Conclusion: No associations were found between leukemia, diabetes, survival and glycemic control., Competing Interests: Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript., (© 2020 Mayo Foundation for Medical Education and Research.)

Aim: To evaluate overall survival (OS), glycemic control in cancer patients with and without diabetes mellitus (DM)., Patients & Methods: Patients (2010-2015) with newly diagnosed prostate, breast, lung, colorectal and pancreatic cancers were identified in institutional cancer registry. Data linked to National Death Index for vital status. 5-year OS estimated; glucose and hemoglobin A 1c assessed during year postdiagnosis., Results: We identified 1404 patients (non-DM, n = 936; DM, n = 468). DM cohort had 168 deaths (36%); non-DM, 267 (29%). 5-year OS estimated at 58% (95% CI: 53-64%) for DM and 67% (95% CI: 64-71%) for controls; for matched pairs, hazard ratio: 1.35 (95% CI: 1.02-1.79). Cancer did not harm glycemic control., Conclusion: OS among cancer patients with DM was lower than without DM., Competing Interests: Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript., (© 2020 Mayo Foundation for Medical Education and Research.)

Objective: To provide an update on key safety metrics after transfusion of convalescent plasma in hospitalized coronavirus 2019 (COVID-19) patients, having previously demonstrated safety in 5000 hospitalized patients., Patients and Methods: From April 3 to June 2, 2020, the US Food and Drug Administration Expanded Access Program for COVID-19 convalescent plasma transfused a convenience sample of 20,000 hospitalized patients with COVID-19 convalescent plasma., Results: The incidence of all serious adverse events was low; these included transfusion reactions (n=78; <1%), thromboembolic or thrombotic events (n=113; <1%), and cardiac events (n=677, ~3%). Notably, the vast majority of the thromboembolic or thrombotic events (n=75) and cardiac events (n=597) were judged to be unrelated to the plasma transfusion per se. The 7-day mortality rate was 13.0% (12.5%, 13.4%), and was higher among more critically ill patients relative to less ill counterparts, including patients admitted to the intensive care unit versus those not admitted (15.6 vs 9.3%), mechanically ventilated versus not ventilated (18.3% vs 9.9%), and with septic shock or multiple organ dysfunction/failure versus those without dysfunction/failure (21.7% vs 11.5%)., Conclusion: These updated data provide robust evidence that transfusion of convalescent plasma is safe in hospitalized patients with COVID-19, and support the notion that earlier administration of plasma within the clinical course of COVID-19 is more likely to reduce mortality., (Copyright © 2020. Published by Elsevier Inc.)

BACKGROUNDConvalescent plasma is the only antibody-based therapy currently available for patients with coronavirus disease 2019 (COVID-19). It has robust historical precedence and sound biological plausibility. Although promising, convalescent plasma has not yet been shown to be safe as a treatment for COVID-19.METHODSThus, we analyzed key safety metrics after transfusion of ABO-compatible human COVID-19 convalescent plasma in 5000 hospitalized adults with severe or life-threatening COVID-19, with 66% in the intensive care unit, as part of the US FDA expanded access program for COVID-19 convalescent plasma.RESULTSThe incidence of all serious adverse events (SAEs), including mortality rate (0.3%), in the first 4 hours after transfusion was <1%. Of the 36 reported SAEs, there were 25 reported incidences of related SAEs, including mortality (n = 4), transfusion-associated circulatory overload (n = 7), transfusion-related acute lung injury (n = 11), and severe allergic transfusion reactions (n = 3). However, only 2 of 36 SAEs were judged as definitely related to the convalescent plasma transfusion by the treating physician. The 7-day mortality rate was 14.9%.CONCLUSIONGiven the deadly nature of COVID-19 and the large population of critically ill patients included in these analyses, the mortality rate does not appear excessive. These early indicators suggest that transfusion of convalescent plasma is safe in hospitalized patients with COVID-19.TRIAL REGISTRATIONClinicalTrials.gov NCT04338360.FUNDINGMayo Clinic, Biomedical Advanced Research and Development Authority (75A50120C00096), National Center for Advancing Translational Sciences (UL1TR002377), National Heart, Lung, and Blood Institute (5R35HL139854 and R01 HL059842), National Institute of Diabetes and Digestive and Kidney Diseases (5T32DK07352), Natural Sciences and Engineering Research Council of Canada (PDF-532926-2019), National Institute of Allergy and Infectious Disease (R21 AI145356, R21 AI152318, and AI152078), Schwab Charitable Fund, United Health Group, National Basketball Association, Millennium Pharmaceuticals, and Octapharma USA Inc.

Background: Inpatient status has been shown to be a predictor of poor bowel preparation for colonoscopy; however, the optimal bowel preparation regimen for hospitalized patients is unknown. Our aim was to compare the efficacy of bowel preparation volume size in hospitalized patients undergoing inpatient colonoscopy., Methods: This prospective, single blinded (endoscopist), randomized controlled trial was conducted as a pilot study at a tertiary referral medical center. Hospitalized patients undergoing inpatient colonoscopy were assigned randomly to receive a high, medium, or low-volume preparation. Data collection included colon preparation quality, based on the Boston Bowel Preparation Scale, and a questionnaire given to all subjects evaluating the ability to completely finish bowel preparation and adverse effects (unpleasant taste, nausea, and vomiting)., Results: Twenty-five colonoscopies were performed in 25 subjects. Patients who received low-volume preparation averaged a higher mean total BBPS (7.4, SD 1.62), in comparison to patients who received high-volume (7.0, SD 1.41) and medium-volume prep (6.9, SD 1.55), P = 0.77. When evaluating taste a higher score meant worse taste. The low-volume group scored unpleasant taste as 0.6 (0.74), while the high-volume group gave unpleasant taste a score of 2.2 (0.97) and the medium-volume group gave a score of 2.1 (1.36), P < 0.01., Conclusion: In this pilot study we found that low-volume colon preparation may be preferred in the inpatient setting due its better rate of tolerability and comparable bowel cleanliness when compared to larger volume preparation, although we cannot overreach any definitive conclusion. Further more robust studies are required to confirm these findings., Trial Registration: The Affect of Low-Volume Bowel Preparation for Hospitalized Patients Colonoscopies., Trial Registration: NCT01978509 (terminated). Retrospectively registered on November 07, 2013.

Introduction: Access to dermatologic care is a major issue in the United States, especially within the un- and underinsured populations; technology, including teledermatology, will pay a role in improving access to care. Methods: We performed a prospective study between November 2016 and September 2017. We leveraged a partnership between Mayo Clinic and Mountain Park Health Clinic, a community clinic that primarily serves un- and underinsured populations. We implemented a mobile phone-based store and forward (SAF) teledermatology service, which integrated an external community health clinic to an existing electronic health record (EHR) using standardized data capture forms, real-time support, and simple workflows. Results: Thirty-seven patients were enrolled in the study, 65% female and 35% male with an average age of 47.9 (SD = 15.9). The ethnic breakdown was: 81.1% Hispanic, 13.5% Caucasian, and 5.4% African American. The majority, 62.2%, did not have a high school education, 45.9% were unemployed, and 51.4% were uninsured. 64.9% earned less than $25,000 for annual household income. Teledermatology consultation increased the absolute diagnostic and management concordance by 36.6% (p  = 0.01, 95% CI 12.2%-61.0%) and 34.2% ( p < 0.01, 95% CI 11%-57%), respectively. Primary care providers had a significant increase in mean confidence in the diagnosis and management of dermatology conditions pre and poststudy (3.60 vs. 3.70 and 3.21 vs. 3.60, respectively; p < 0.01). Ninety-six percent of the primary care providers agreed (52.0%) and strongly agreed (44.0%) that they would send another patient for teleconsultation. Conclusion: We successfully implemented a SAF teledermatology consultative service in a community health clinic outside our EHR. A similar approach can be used by other large health care organizations to provide integrated, high-quality consultation to clinics with rural, un- and underinsured populations.

Patients admitted to a medical-surgical unit infrequently require early transfer to higher level care, although how their inpatient length of stay compares to untransferred patients, or those directly admitted to intermediate care, is unknown. We sought to compare the inpatient length of stay of these groups., Design: Single-site retrospective analysis., Setting: An academic hospital specializing in complex care., Patients: We evaluated 23,694 patients admitted to the Hospital Internal Medicine service over a 4-year period (January 1, 2013, to December 31, 2016)., Interventions: None., Measurements and Main Results: Using 6- and 24-hour definitions of early transfer, we categorized patients as admitted to medical-surgical unit without early transfer (medical-surgical unit), transferred (TX) early to higher level care, or initially admitted to an intermediate care unit. We report patient characteristics and inpatient length of stay adjusted for patient demographics (age and sex) and initial acuity (measured by Emergency Severity Index). There were significant increases in both unadjusted inpatient length of stay (6 hr: medical-surgical unit = 73.4 hr, TX = 137.9 hr, intermediate care unit = 101.1 hr; 24 hr: medical-surgical unit = 72.4 hr, TX = 141.9 hr, intermediate care unit = 98.2 hr; p < 0.01 for all groups) and adjusted inpatient length of stay (6-hr definition: medical-surgical unit = 50.9 hr [95% CI, 50.3-51.6 hr], TX = 100.4 hr [90.4-112.0 hr], intermediate care unit = 72.3 hr [70.6-74.0 hr]; 24-hr definition: medical-surgical unit = 50.3 hr [49.7-50.9 hr], TX = 108.3 hr [101.5-116.0 hr], intermediate care unit = 70.7 hr [69.0-72.3 hr]; p < 0.0001 for comparison of TX to medical-surgical unit and intermediate care unit in both groups). The increases in inpatient length of stay for the TX groups were not explained by differences in demographics or acuity., Conclusions: In a single facility study, patients admitted to a medical/surgical unit who require early transfer to intermediate care unit have a significant and unexplained increase in inpatient length of stay. This unexplained increased inpatient length of stay suggests that triage to the appropriate inpatient unit significantly affects inpatient length of stay., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background: The King-Devick test is a timed rapid number naming task that involves complex cerebral functions. The objective of this pilot exploratory study is to determine whether there is a difference in the King-Devick test during a migraine attack compared to the interictal phase., Methods: We evaluated 29 adult subjects with migraine with aura or migraine without aura. For each participant, we performed King-Devick tests during migraine attacks and interictal phases. Subjects served as their own controls., Results: The King-Devick test was slower during the migraine attack compared to the interictal baseline (median 4.6 sec slower, p  < 0.001). The slowing of the King-Devick test during migraine attack was more prominent in those with migraine with aura compared to subjects with migraine without aura (median 7.5 vs. 2.8 sec, p  = 0.028)., Conclusions: This exploratory, observational study shows changes in the King-Devick test during migraine compared to the interictal phase. Future studies are required to determine if the King-Devick test may be used as a rapid and simple tool to objectively characterize migraine-associated disability.

Background: The main factor that limits wider utilization of capsule endoscopy (CE) in Crohn's disease (CD) is the potential risk of retention. The aim of this systematic review was to evaluate capsule retention rates in adult and pediatric CD and determine if retention risk is reduced in established CD (ECD) with patency capsule (PC) or magnetic resonance/computed tomography (MR/CT) enterography., Methods: Studies of CD patients undergoing CE that reported retention were identified. Pooled estimates for retention rates and relative risk in ECD to suspected CD (SCD) were calculated. All hypothesis tests were 2-sided; statistical significance was set at a P value of <0.05., Results: In the overall CD cohort, retention rates were 3.32% (95% confidence interval [CI], 2.62%-4.2%): 4.63% (95% CI, 3.42%-6.25%) and 2.35% (95% CI, 1.31%-4.19%) in ECD and SCD, respectively. Retention rates were 3.49% (95% CI, 2.73%-4.46%) and 1.64% (95% CI, 0.68%-3.89%) in adult and pediatric CD, respectively. Retention risk in adult ECD was 3.4 times higher than SCD, but there was no difference in retention risk in pediatric ECD compared with SCD. Retention rates in ECD were decreased after patency capsule (2.88%; 95% CI, 1.74%-4.74%) and MR/CT enterography (2.32%; 95% CI, 0.87%-6.03%)., Conclusions: In comparison with older literature, this meta-analysis demonstrates lower CE retention rates in SCD and ECD. Retention rates in pediatric CD were lower than in adult CD. Retention rates in adult ECD were higher than SCD, but there were no differences between pediatric ECD and SCD. Retention rates in ECD were lower after negative PC or MR/CT enterography., (© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Little research has been done in teledermatology to examine the effects of standardized templates and subject-specific learning modules., Methods: We performed a prospective study examining the effects of standardized templates and standardized cutaneous oncology learning modules on teledermatology referrals at Mayo Clinic. This data was then compared to previous teledermatology referrals before standardized templates were adopted., Results: A total of 42 teledermatology consultations were performed during the 4-month study period. The use of standardized templates resulted in an absolute reduction in face-to-face referrals. Teledermatology consultation increased the absolute diagnostic and management concordance by 26.2% (P = 0.02) and 33.3% (P < 0.01), respectively, and decreased the absolute diagnostic and management discordance by 19.1% (P = 0.03) and 31.0% (P < 0.01), respectively. The largest knowledge gaps were identified in cutaneous oncology. Educational intervention improved theoretical referral rates and confidence in diagnosis and management overall., Conclusion: The implementation of standardized intake templates reduces the rate of face-to-face referrals. Teledermatology improves primary care-based dermatological care and reduces theoretical referral rates., (© 2019 The International Society of Dermatology.)

Drug screening during pre-transplant evaluations can have major implications for patient care, particularly because drug abuse has been associated with poor transplant outcomes. Although urine drug screening is usually preferred, serum testing is available for situations such as anuria due to end stage renal disease. However, there are few studies evaluating serum drug screening in specific populations such as patients undergoing kidney transplant evaluation. All serum drug screens ordered between January 2015 and November 2017 on patients being evaluated for renal transplant were compared against a large population of serum drug screens ordered from other institutions. Cocaine screening and confirmation results were evaluated to determine false positives. Cocaine screens were positive in 23 of 537 (4.3%) pre-transplant samples, and 211 of 5,115 (4.1%) comparison samples. Confirmation testing demonstrated that 14 (60.9%) pre-transplant samples were false positives, which was significantly (P < 0.01) higher than the rate of false positives in the comparison group (47/211, 22.3%). No common medication or other cross-reacting substance could be identified in the pre-transplant cohort to explain the false-positive results. Although serum cocaine screening had a low overall false-positive rate, the proportion of false positives was significantly higher in pre-transplant patients. Given the poor transplant outcomes associated with drug abuse, failure to properly interpret screening results as being false positives could negatively affect patient care. All members of the transplant team should recognize the importance of confirmation testing in this setting, to avoid unintended consequences due to false-positive screening results., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: To report the outcomes of sinonasal tumors treated with proton beam therapy (PBT) on the Proton Collaborative Group registry study., Methods and Materials: Sixty-nine patients with sinonasal tumors underwent curative intent PBT between 2010 and 2016. Patients who received de novo irradiation (42 patients) were analyzed separately from those who received reirradiation (27 patients) (re-RT). Median age was 53.1 years (range, 15.7-82.1; de novo) and 57.4 years (range, 31.3-88.0; re-RT). The most common histology was squamous cell carcinoma in both groups. Median PBT dose was 58.5 Gy (RBE) (range, 12-78.3; de novo) and 60.0 Gy (RBE) (range 18.2-72.3; re-RT), and median dose per fraction was 2.0 Gy (RBE) for both cohorts. Survival estimates for patients who received de novo irradiation and those who received re-RT were calculated using the Kaplan-Meier method., Results: Median follow-up for surviving patients was 26.4 months (range, 3.5-220.5). The 3-year overall survival (OS), freedom from distant metastasis, freedom from disease progression, and freedom from locoregional recurrence (FFLR) for de novo irradiation were 100%, 84.0%, 77.3%, and 92.9%, respectively. With re-RT, the 3-year OS, freedom from distant metastasis, FFDP, and FFLR were 76.2%, 47.4%, 32.1%, and 33.8%, respectively. In addition, 12 patients (17.4%) experienced recurrent disease. Re-RT was associated with inferior FFLR ( P = . 04). On univariate analysis, squamous cell carcinoma was associated with inferior OS ( P < . 01) for patients receiving re-RT. There were 11 patients with acute grade 3 toxicities. Late toxicities occurred in 15% of patients, with no grade ≥3 toxicities. No patients developed vision loss or symptomatic brain necrosis., Conclusions: As one of the largest studies of sinonasal tumors treated with PBT, our findings suggest that PBT may be a safe and efficacious treatment option for patients with sinonasal tumors., (© 2019 The Authors.)