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Joseph L Reno,1 Michael Kushelev,2 Julie H Coffman,3 Mona R Prasad,4 Avery M Meyer,5 Kristen M Carpenter,5 Marilly S Palettas,6 John C Coffman2 1Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA; 2Department of Anesthesiology, The Ohio State University Medical Center, Columbus, OH, USA; 3Department of Internal Medicine, Riverside Methodist Hospital, Columbus, OH, USA; 4Department of OBGYN, OhioHealth, Columbus, OH, USA; 5Department of Psychiatry and Behavioral Health, The Ohio State University Wexner Medical Center, Columbus, OH, USA; 6Center for Biostatistics, The Ohio State University, Columbus, OH, USACorrespondence: Joseph L Reno Tel +1 206 543 2673Fax +1 206 543 2958Email renoj@uw.eduBackground: Despite the increasing prevalence of opioid use disorder (OUD) in pregnant women, there are limited studies on their anesthesia care and analgesic outcomes after cesarean delivery (CD).Methods: Patients with OUD on either buprenorphine or methadone maintenance therapy who underwent CD at our institution from 2011 to 2018 were identified. Anesthetic details and analgesic outcomes, including daily opioid consumption and pain scores, were compared between patients maintained on buprenorphine and methadone. Analgesic outcomes were also evaluated according to anesthetic type (neuraxial or general anesthesia) and daily buprenorphine/methadone dose to determine if these factors impacted pain after delivery.Results: A total of 146 patients were included (buprenorphine n=99 (67.8%), methadone n=47 (32.2%)). Among all patients: 74% had spinal/CSE, 15% epidural, and 11% general anesthesia. Anesthesia types were similar among buprenorphine and methadone patients. For spinal anesthetics, intrathecal fentanyl (median 15 μg) and morphine (median 100 μg) were commonly given (97.2% and 96.3%, respectively), and dosed similarly between groups. Among epidural anesthetics, epidural morphine (median 2 mg) was commonly administered (90.9%), while fentanyl (median 100 μg) was less common (54.5%). Buprenorphine and methadone groups consumed similar amounts of oxycodone equivalents per 24 hours of hospitalization (80.6 vs 76.3 mg; p=0.694) and had similar peak pain scores (8.3 vs 8.0; p=0.518). Daily methadone dose correlated weakly with opioid consumption (R=0.3; p=0.03), although buprenorphine dose did not correlate with opioid consumption or pain scores. General anesthesia correlated with greater oxycodone consumption in the first 24 hours (median 156.1 vs 91.7 mg; p=0.004) and greater IV PCA use (63% vs 7%; p< 0.001) compared to neuraxial anesthesia.Conclusion: Patients on buprenorphine and methadone had similar high opioid consumption and pain scores after CD. The anesthetic details and analgesic outcomes reported in this investigation may serve as a useful reference for future prospective investigations and aid in the clinical care of these patients.Keywords: opioid use disorder, methadone, buprenorphine, cesarean analgesia, outcomes, enhanced recovery

Purpose: Neoadjuvant therapy (NT) is increasingly used for gastrointestinal (GI) and hepatopancreatobiliary (HPB) cancers. Risk factors for surgical attrition during NT are poorly understood. A planned secondary analysis of patient-reported outcomes (PROs) from a prospective cohort study of patients undergoing NT was performed to identify factors associated with surgical attrition., Methods: Adult patients with GI/HPB cancer receiving NT were provided a mobile phone application administering QOL assessments every 30 days and measuring mood/symptoms until NT completion. Univariate and multivariate logistic regression were performed to determine the association between demographic, clinical characteristics, and PROs with surgical attrition (no surgery (NS) versus surgery or watchful waiting (SWW)). Mixed-effects regression models evaluated trends of QOL and symptoms between the cohorts., Results: Among 104 enrolled patients, mean age was 60.5 ± 11.5 years, 57 (55%) were male, and 95 (91%) were Caucasian. After a mean duration of 3.4 months of NT, 76 (73%) patients underwent SWW, while 28 (27%) did not (NS). Cancer type (HPB vs GI, OR 7.0, CI 2.7-19.3, p < 0.001), comorbidities (OR 1.72, CI 1.0-2.99, p = 0.05), and severe complications during NT (OR 4.2, CI 1.2-15.3, p = 0.03) were associated with NS. There were no differences between longitudinal QOL scores or PROs among patients who underwent SWW versus NS except for the lack of appetite, which was associated with NS (OR 3.6, CI 1.0-12.2, p = 0.04)., Conclusions: Among patients undergoing NT for GI/HPB malignancies, type of cancer, comorbidities, and severe complications during NT were associated with failure to undergo surgery, whereas QOL and PROs were largely not., Competing Interests: Declarations. Ethics Approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the clinical scientific review committee and institutional review board of The Ohio State University (#2020C0071). Consent to Participate: Informed consent was obtained from all individual participants included in the study. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Shortening analgesic onset has been researched and it has been documented that prewarming epidural medications to body temperature (37°C) prior to administration increases medication efficacy. Our double-blind randomized controlled trial was designed to investigate if a lower degree of prewarming in providers' pockets could achieve similar results without the need of a bedside incubator. A total of 136 parturients were randomized into either the pocket-warmed group or the room temperature group to receive 10 mL of 0.125% bupivacaine with 2 μg/mL fentanyl epidural bolus at either the 27.8 ±1.7°C or 22.1 ±1.0°C temperatures, respectively. Primary outcome, time to analgesic onset (verbal rating scale pain score ≤ 3) was recorded in 0-, 5-, 10-, 15-, 20-, 30-, and 60-minutes intervals. It was observed that the pocket-warming group (n = 64) and room temperature group (n = 72) had no significant difference of analgesic onset time (median 8 vs. 6.2 minutes; p = 0.322). The incidence of adverse events such as hypotension, fever (≥ 38°C), nausea, vomiting, and number of top-off epidural boluses, as well as patient satisfaction rates and mode of delivery, were not significantly different between the groups as well. Further research is warranted to confirm these findings and explore the impact of different temperatures on analgesic onset time as well as the logistical issues associated with their clinical implementations., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Balon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Peripheral nerve stimulation (PNS) is an emerging neuromodulation modality, yet there remains limited data highlighting its long-term effectiveness. The objective of this study was to report real-world data on pain intensity and opioid consumption after temporary and permanent PNS for chronic pain up to 24 months postimplantation., Methods: A retrospective study was conducted on all patients who received PNS implants at a multi-centered enterprise between January 1, 2014 and February 24, 2022. The two co-primary outcomes were: (1) change in pain intensity (11-point Numerical Rating Scale) from baseline to 12 months postimplant; and (2) comparison of the change in pain intensity between temporary and permanent PNS cohorts 12 months postimplant., Results: 126 patients were included in this analysis. Pain intensity significantly decreased 12 months postimplant in the overall cohort (mean difference (MD) -3.0 (95% CI -3.5 to -2.4), p<0.0001). No significant difference in this reduction was identified between temporary and permanent PNS cohorts (MD 0.0 (95% CI -1.1 to 1.0), p=1.00) 12 months postimplantation. Pain intensity significantly decreased in the overall, temporary, and permanent cohorts at all secondary time points (3, 6, and 24 months). No change in daily opioid consumption was observed at 6 and 12 months postimplant in the overall cohort., Conclusion: This study found that both temporary and permanent PNS may be effective for reducing pain intensity in patients with chronic pain up to 24 months postimplantation, although no changes in opioid consumption were observed. The decrease in pain intensity was comparable between patients receiving temporary versus permanent implants, highlighting that temporary PNS may achieve long-lasting clinical benefits. However, given the substantial loss to follow-up, further large-scale studies are needed to solidify conclusions about the efficacy of PNS., Competing Interests: Competing interests: AB has received consultancy fees from Medtronic and Bioventus. His institution has also received funding for studies to track outcomes of neuromodulation therapies from Medtronic. RSD has received investigator-initiated grant funding paid to his institution from Nevro Corp and Saol Therapeutics., (© American Society of Regional Anesthesia & Pain Medicine 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Purpose: Effective cancer care coordination (CCC) is an integral component of health care delivery and critical to achieving optimal oncologic outcomes. Neoadjuvant therapy (NT), the delivery of multimodality therapy prior to surgery, is inherently complex and multidisciplinary, but CCC during NT is poorly understood. The objective of this study was to characterize patient perceptions of CCC during NT using a mixed methods approach., Methods: This study is a cross-sectional analysis of patients with gastrointestinal cancers receiving NT who participated in a prospective longitudinal cohort study evaluating their real-time experience using a customized smartphone application. Patients completed the Cancer Care Coordination Questionnaire for Patients (CCCQ-P), a 20-item validated measure of care coordination quality, six weeks after initiating NT. Items were scored on a 5-point Likert scale, and subsections on communication (13 questions) and navigation (7 questions) were calculated with higher scores signifying better CCC. Univariate linear regression was used to calculate the impact of fragmented care and other factors on perceived CCC. Semi-structured interviews were conducted among a convenience sample of patients (n = 5); transcribed interviews were then coded using an inductive approach., Results: Among 82 participants, mean age was 61 years old, 68% were male, and mean number of comorbidities was 1.68. Overall (mean 76.6 out of 100), communication subsection (48.6 out of 65), and navigation subsection (28.0 out of 35) CCCQ-P scores suggested overall positive perceptions of care coordination. Qualitative analysis of patient interviews highlighted the need for coordination among physicians before communicating the plan to patients as well as the importance of providers communicating plans in verbal and written form., Conclusions: Successful completion of NT requires significant care coordination between patients and healthcare professionals. Yet, in this cross-sectional analysis of patients on a prospective cohort study, patient perceptions of CCC during NT were overall positive. Future research should focus on optimizing other aspects of care delivery in order to improve outcomes of NT., (© 2024. The Author(s).)

Objective: To use a customized smartphone application to prospectively measure QOL and the real-time patient experience during neoadjuvant therapy (NT)., Background: NT is increasingly used for patients with localized gastrointestinal (GI) cancers. There is little data assessing patient experience and quality of life (QOL) during NT for GI cancers., Methods: Patients with GI cancers receiving NT were instructed on using a customized smartphone application through which the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire, a validated measure of health-related QOL, was administered at baseline, every 30 days, and at the completion of NT. Participants also tracked their moods and symptoms and used free-text journaling functionalities in the application. Mean overall and subsection health-related QOL scores were calculated during NT., Results: Among 104 enrolled patients, the mean age was 60.5 ± 11.5 years and 55% were males. Common cancer diagnoses were colorectal (40%), pancreatic (37%), and esophageal (15%). Mean overall FACT-G scores did not change during NT ( P = 0.987). While functional well-being scores were consistently the lowest and social well-being scores the highest, FACT subscores similarly did not change during NT (all P > 0.01). The most common symptoms reported during NT were fatigue, insomnia, and anxiety (39.3%, 34.5%, and 28.3% of patient entries, respectively). Qualitative analysis of free-text journaling entries identified anxiety, fear, and frustration as the most common themes, but also the importance of social support systems and confidence in health care providers., Conclusions: While patient symptom burden remains high, results of this prospective cohort study suggest QOL is maintained during NT for localized GI cancers., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Venous thromboembolism (VTE) is a dangerous postoperative complication after abdominal wall reconstruction (AWR). Intraoperative core body temperature has been associated with thrombotic events in other surgical contexts. This study examines the effects of intraoperative temperature on VTE rate after AWR., Methods: A retrospective study was performed on AWR patients. Cohorts were defined by postoperative 30-day VTE. Intraoperative core body temperature was recorded as the minimum, maximum, and mean intraoperative temperatures. Study variables were analyzed with logistic regression and cutoff analysis to assess for association with VTE., Results: In total, 344 patients met inclusion criteria. Fourteen patients were diagnosed with 30-day VTE for an incidence of 4.1%. The VTE cohort had a longer median inpatient stay (8 days versus 5 days, P < 0.001) and greater intraoperative change in peak inspiratory pressure (3 mm H 2 O versus 1 mm H 2 O, P = 0.01) than the non-VTE cohort. Operative duration [odds ratio (OR) = 1.32, P = 0.01], length of stay (OR = 1.07, P = 0.001), and intraoperative PIP difference (OR = 1.18, P = 0.045) were significantly associated with 30-day VTE on univariable regression. Immunocompromised status (OR = 4.1, P = 0.023; OR = 4.0, P = 0.025) and length of stay (OR = 1.1, P < 0.001; OR = 1.1, P < 0.001) were significant predictors of 30-day VTE on two multivariable regression models. No significant associations were found between temperature metrics and 30-day VTE on cutoff point or regression analysis., Conclusions: Intraoperative core body temperature did not associate with 30-day VTE after AWR, though operative duration, length of stay, immunocompromised status, and intraoperative PIP difference did. Surgeons should remain mindful of VTE risk after AWR, and future research is warranted to elucidate all contributing factors., Competing Interests: Dr. Janis receives royalties from Thieme and Springer Publishing. The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Background: The 2021 Surviving Sepsis Campaign Guidelines recommend the use of hydrocortisone in patients who remain hemodynamically unstable despite adequate fluid resuscitation and vasopressor therapy. Fludrocortisone has been used concomitantly with hydrocortisone in some studies without a clearly defined role or known clinical benefit. The purpose of this study was to assess the impact of fludrocortisone added to hydrocortisone on shock-free days for septic shock., Methods: A single-center, retrospective propensity score-weighted study was conducted to compare hydrocortisone versus hydrocortisone plus fludrocortisone for septic shock. Adults admitted to the medical intensive care unit (ICU) from 2015 to 2020 were included in the study. All patients received ≥200 mg/day hydrocortisone for at least 24 h ± fludrocortisone initiated within 72 h of vasopressors. The primary outcome was shock-free days by day 14. The secondary outcomes included duration of shock, change in Sequential Organ Failure Assessment (SOFA) score, hospital and ICU length of stay, and all-cause inhospital mortality., Results: A total of 228 patients met inclusion criteria with 212 patients retained after propensity score weighting. There was no difference between groups in 14-day shock-free days (6.3 vs. 6.1 days; P = 0.781). Furthermore, no significant differences were observed for the secondary outcomes of ICU/hospital length of stay, duration of shock, change in SOFA score, and all-cause inhospital mortality., Conclusion: The addition of fludrocortisone to hydrocortisone in septic shock did not increase shock-free days by day 14. These results suggest that the use of hydrocortisone alone may be an adequate adjunctive therapy in septic shock. A prospective randomized controlled trial is needed to confirm results., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 International Journal of Critical Illness and Injury Science.)

Background: Trigger point deactivation surgery is a safe and effective treatment for properly selected patients experiencing migraine, with 68.3%-100% experiencing symptom improvement postoperatively. However, it is still unknown why certain patients do not respond. Obesity has been shown to be associated with worsened migraine symptoms and a decreased response to select pharmacotherapies. This study aimed to determine whether obesity may also be associated with an attenuated response to surgery., Methods: A retrospective chart review was conducted to identify patients who had undergone trigger point deactivation surgery for migraine. Patients were split into obese and nonobese cohorts. Obesity was classified as a body mass index of 30 or higher per Centers for Disease Control and Prevention guidelines. Outcomes and follow-up periods were determined with respect to individual operations. Outcomes included migraine attack frequency, intensity, duration, and the migraine headache index. Differences in demographics, operative characteristics, and operative outcomes were compared., Results: A total of 62 patients were included in the study. The obese cohort comprised 31 patients who underwent 45 total operations, and the nonobese cohort comprised 31 patients who underwent 34 operations. Results from multivariable analysis showed no impact of obesity on the odds of achieving a more than 90% reduction in any individual outcome. The overall rates of improvement (≥50% reduction in any outcome) and elimination (100% reduction in all symptoms) across both cohorts were 89.9% and 65.8%, respectively., Conclusion: Obese patients have outcomes comparable to a nonobese cohort after trigger point deactivation surgery for migraine., Competing Interests: Dr. Janis receives royalties from Thieme and Springer Publishing. All of the other authors have no financial interest to declare in relation to the content of this article., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Background: Malignant pleural effusions (MPE) can cause severe dyspnoea leading to greater than 125 000 hospitalisations per year and cost greater than US$5 billion per year in the USA. Timely insertion of tunnelled pleural catheters (TPCs) is associated with fewer inpatient days and emergency department visits. We conducted a quality improvement study to reduce hospital admissions of patients with MPE., Methods: Key stakeholders were surveyed, including thoracic and breast oncology teams, general pulmonary and interventional pulmonology (IP) to help identify the underlying causes and solutions. Our preintervention group consisted of 51 patients who underwent TPC placement by our IP service. In our first intervention, we reviewed referrals for MPE with the scheduling team and triaged them based on urgency. In the second intervention, we added a follow-up phone call 1 week after the initial thoracentesis performed by IP to assess for the recurrence of symptoms., Results: Demographic and clinical characteristics were summarised across the three groups. We evaluated the rate ratio (RR) of admissions in the intervention groups with the multivariable Poisson regression and adjusted for race, gender and cancer. Compared with the preintervention group, intervention I showed trends towards a 41% lower hospital admission rate (RR 0.59 (0.33-1.07), p=0.11). Compared with the preintervention group, intervention II showed trends towards a 40% lower hospital admission rate (RR 0.6 (0.36-0.99), p=0.07). The results did not reach statistical significance. Exploratory comparisons in readmission rates between interventions I and II showed no difference (RR 0.89 (0.43-1.79), p=0.75)., Conclusions: Both interventions showed trends toward fewer hospital readmissions although they were not statistically significant. Larger-size prospective studies would be needed to demonstrate the continued effectiveness of these interventions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Migraine headaches and obesity are both prevalent disorders, resulting in a high socioeconomic burden. To better understand the relationship between obesity and migraine, the aim of this study was to investigate the association between migraine severity, metabolic syndrome and estrogen-associated variables. A retrospective analysis of adult patients with refractory migraine seen by our senior author (J.E.J.) was performed. Patient demographics and migraine characteristics, including migraine intensity, duration, and number of headaches per month were collected from medical records. Migraine headache index (MHI) was calculated by multiplying frequency, intensity and duration of headaches. Weight and height were used to calculate body mass index (BMI) and these were divided per Center for Disease Control (CDC) classifications. Univariate linear regression models were used to evaluate associations. Patients (n = 223) were predominantly female (78%) with a mean age of 44 years at presentation. Patients with a BMI higher than 40 (class 3 obesity) had a higher MHI (p = 0.01) and experienced a higher number of migraines per month (p = 0.007), compared to patients with a healthy BMI, respectively. Migraine frequency was found to be significantly higher in post-menopausal women compared to pre-menopausal women (p = 0.02). No other significant associations were found. This study found that severe obesity (BMI > 40) is associated with increased migraine severity and frequency. Post-menopausal patients are also found to have increased migraine frequency, which could be explained by the estrogen-withdrawal hypothesis. Future studies are needed to evaluate the outcomes of individuals with obesity after nerve deactivation surgery., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Neoadjuvant therapy (NT) is increasingly used before surgery for patients with gastrointestinal (GI) cancers. Treatment burden is a patient-centered measure defined as the work of being a patient and characterizes the impact of medical treatment on one's functioning and well-being. While treatment burden has previously been studied in chronic diseases and cancer survivorship, the treatment burden of undergoing NT is unknown., Methods: All patients enrolled in a prospective cohort study evaluating the real-time experience of NT for GI cancers completed either the Patient Experience with Treatment and Self-management (PETS) survey, a 46-item validated measure of treatment burden, or the mini-PETS questionnaire. PETS subsections were scored on a 5-point Likert scale and then standardized on a 100-point scale (a higher number means more treatment burden). Semistructured interviews were conducted among a convenience sample of patients (n = 5); qualitative data were coded and then analyzed using an integrated approach., Results: Among 126 participants, the mean age was 59 years old, 61% were male, and the mean number of comorbidities was 1.57. The most common cancers were colorectal (46%) and pancreatic (28%). The mean length of NT treatment was 3.7 months and 80.2% of patients underwent surgical resection following NT. The highest standardized treatment burden scores were observed in healthcare services (44 ± 15), social limitations (44 ± 26), exhaustion (41 ± 23), and medical expenses (40 ± 18) whereas the lowest scores were reported in medication use (19 ± 16) and interpersonal challenges (19 ± 17). Commonly experienced emotional symptoms were feeling worn out (43%) or frustrated (32%). No significant differences were observed in mean treatment burden subscores between patients who underwent surgery versus those who did not. Qualitative analysis of treatment burden during NT identified common themes of impact on normal life activities, challenges with healthcare access, impact on relationships, and significant physical and emotional symptoms., Conclusions: NT is associated with a significant treatment burden, particularly in the domains of accessing healthcare services, social limitations, and exhaustion. Given the increasing use of NT for GI cancers, novel patient-centered approaches are needed to improve quality of life and ensure the completion of multimodality therapy., (© 2023 The Authors. Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Background: Falls of inpatients are common in hospitals. Existing fall prevention measures do not work consistently., Purpose: To determine whether Smart Socks reduce fall rates in fall risk patients at a major academic health center's neurological and neurosurgical based units., Methods: A prospective study was conducted that provided fall risk patients with Smart Socks and no other fall prevention system. Data collected included duration of Smart Socks wearing, number of alarms, response times, and patient-days., Results: A total of 569 fall risk patients were included for 2211.6 patient-days. There were 4999 Smart Socks alarms, but none of the patients fell. We observed a lower fall rate, of 0 per 1000 patient-days, for patients wearing Smart Socks than the historical fall rate of 4 per 1000 patient-days. The median nurse response time was 24 seconds., Conclusions: The Smart Socks reduced fall rates of fall risk patients included in the study., Competing Interests: The authors declare they have no financial or any other relationship with Palarum LLC. The authors declare no other conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Acalabrutinib, a next-generation Bruton's tyrosine kinase inhibitor (BTKi), associates with dramatic efficacy against B-cell malignancies. Recently, unexplained ventricular arrhythmias (VAs) with next-generation BTKi-therapy have been reported. Yet, whether acalabrutinib associates with VAs in long-term follow-up is unknown. Leveraging a large-cohort of 290 consecutive B-cell malignancy patients treated with acalabrutinib from 2014 to 2020, we assessed the incidence of VAs. The primary-endpoint was incident VA development (ventricular fibrillation, ventricular tachycardia, and symptomatic premature ventricular contractions). Probability-scores were assessed to determine likelihood of acalabrutinib-association. Incident rates as function of time-on-therapy were calculated. Weighted average observed incidence rates were compared with expected population rates using relative-risks. Absolute excess risk (AER) for acalabrutinib-associated VAs was estimated. Over 1063 person-years of follow-up, there were 8 cases of incident-VAs, including 6 in those without coronary disease (CAD) or heart failure (HF) and 1 sudden-death; median time-to-event 14.9 months. Among those without prior ibrutinib-use, CAD, or HF, the weighted average incidence was 394 per 100 000 person years compared with a reported incidence of 48.1 among similar-aged non-BTKi-treated subjects (relative risk, 8.2; P < .001; AER, 346). Outside of age, no cardiac or electrocardiographic variables associated with VA development. Collectively, these data suggest VAs may be a class-effect of BTKi therapies., (© 2022 by The American Society of Hematology.)

Background: Clinical pharmacists are often used to make recommendations regarding tacrolimus therapy in the post transplant setting.Therapeutic drug monitoring (TDM) of tacrolimus after transplant is based on trough levels in the setting of predetermined institutional immunosuppression goals. To evaluate time within therapeutic range (TTR) of tacrolimus the Rosendaal method can be utilized., Objective: Our study aimed to compare objective therapeutic drug monitoring outcomes after the implementation of a pharmacist driven tacrolimus management protocol (postprotocol initiation) with previous management by providers (preprotocol initiation)., Practice Description: The Ohio State University Wexner Medical Center (OSUWMC) is a 700-bed academic medical center in Columbus, OH. On average, OSUWMC completes more than 300 kidney transplants each year. There are 6 abdominal transplant pharmacists (including one postgraduate year 2 transplant pharmacy resident) that rotate through the inpatient and outpatient setting., Practice Innovation: A pharmacist-led tacrolimus management protocol in kidney transplant recipients was initiated in October 2018 at our institution, which enabled pharmacists to dose and adjust tacrolimus in the outpatient setting in accordance with prespecified goals., Evaluation Methods: This single-center retrospective analysis included adult kidney transplant recipients on de novo tacrolimus. Patient's tacrolimus levels were evaluated for 6 months after transplant. The mean tacrolimus percent TTR and the median coefficient of variation (CV) were calculated and compared in postprotocol initiation group (n = 85) with preprotocol initiation group (n = 39). TTR was calculated using the Rosendaal method., Results: There was no statistically significant difference between the preprotocol initiation and postprotocol initiation group mean TTR (59.6% vs. 60.5%, P = 0.723), mean CV from 0-3 months after transplant (36.3 vs. 36.0, P = 0.900), and mean CV from at least 3-6 months after transplant (24.5 vs. 22.7, P = 0.351). Rejection rates, development of donor-specific antibodies, and renal function were similar between groups., Conclusion: Based on our findings, transplant pharmacists were equally as effective at maintaining tacrolimus percent TTR and CV in the designated kidney transplant recipients included in the management protocol compared with primary management by other transplant providers. The delegation of tacrolimus management to clinical pharmacists is a viable alternative to primary management by outpatient practitioners., (Copyright © 2022 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Background: Pectoralis nerve blocks (PECS) have been shown in numerous studies to be a safe and effective method to treat postoperative pain and reduce postoperative opioid consumption after breast surgery. However, there are few publications evaluating the PECS block effectiveness in conjunction with multimodal analgesia (MMA) in outpatient breast surgery. This retrospective study aims to evaluate the efficacy of PECS's blocks on perioperative pain management and opioid consumption., Methods: We conducted a retrospective study to assess the efficacy of preoperative PECS block in addition to preoperative MMA (oral acetaminophen and/or gabapentin) in reducing opioid consumption in adult female subjects undergoing outpatient elective breast surgery between 2015 and 2020. A total of 228 subjects were included in the study and divided in two groups: PECS block group (received PECS block + MMA) and control Group (received only MMA). The primary outcome was to compare postoperative opioid consumption between both groups. The secondary outcome was intergroup comparisons of the following: postoperative nausea and vomiting (PONV), incidence of rescue antiemetic medication, PACU non-opioid analgesic medication required, length of PACU stay and the incidence of 30-day postoperative complications between both groups., Results: Two hundred and twenty-eight subjects ( n = 228) were included in the study. A total of 174 subjects were allocated in the control group and 54 subjects were allocated in the PECS block group. Breast reduction and mastectomy/lumpectomy surgeries were the most commonly performed procedures (48% and 28%, respectively). The total amount of perioperative (intraoperative and PACU) MME was 27 [19, 38] in the control group and 28.5 [22, 38] in the PECS groups ( p = 0.21). PACU opioid consumption was 14.3 [7, 24.5] MME for the control group and 17 [8, 23] MME (p = 0.732) for the PECS group. Lastly, the mean overall incidence of postsurgical complications at 30 days was 3% ( N = 5), being wound infection, the only complication observed in the PECS groups ( N = 2), and hematoma ( N = 2) and wound dehiscence ( N = 1) in the control group., Conclusion: PECS block combined with MMA may not reduce intraoperative and/or PACU opioid consumption in patients undergoing outpatient elective breast surgery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Uribe, Weaver, Echeverria-Villalobos, Periel, Pasek, Fiorda-Diaz, Palettas, Skoracki, Poteet and Heard.)

Background: Post-market analyses revealed unanticipated links between first-generation Bruton's tyrosine kinase inhibitor (BTKi) therapy, ibrutinib, and profound early hypertension. Yet, whether this is seen with novel selective second (next)-generation BTKi therapy, acalabrutinib, is unknown., Methods: Leveraging a large cohort of consecutive B cell cancer patients treated with acalabrutinib from 2014 to 2020, we assessed the incidence and ramifications of new or worsened hypertension [systolic blood pressure (SBP) ≥ 130 mmHg] after acalabrutinib initiation. Secondary endpoints were major cardiovascular events (MACE: arrhythmias, myocardial infarction, stroke, heart failure, cardiac death) and disease progression. Observed incident hypertension rates were compared to Framingham heart-predicted and ibrutinib-related rates. Multivariable regression and survival analysis were used to define factors associated with new/worsened hypertension and MACE, and the relationship between early SBP increase and MACE risk. Further, the effect of standard antihypertensive classes on the prevention of acalabrutinib-related hypertension was assessed., Results: Overall, from 280 acalabrutinib-treated patients, 48.9% developed new/worsened hypertension over a median of 41 months. The cumulative incidence of new hypertension by 1 year was 53.9%, including 1.7% with high-grade (≥ 3) hypertension. Applying the JNC 8 cutoff BP of ≥ 140/90 mmHg, the observed new hypertension rate was 20.5% at 1 year, > eightfold higher than the Framingham-predicted rate of 2.4% (RR 8.5, P < 0.001), yet 34.1% lower than ibrutinib (12.9 observed-to-expected ratio, P < 0.001). In multivariable regression, prior arrhythmias and Black ancestry were associated with new hypertension (HR 1.63, HR 4.35, P < 0.05). The degree of SBP rise within 1 year of treatment initiation predicted MACE risk (42% HR increase for each + 5 mmHg SBP rise, P < 0.001). No single antihypertensive class prevented worsened acalabrutinib-related hypertension., Conclusions: Collectively, these data suggest that hypertension may be a class effect of BTKi therapies and precedes major cardiotoxic events., (© 2022. The Author(s).)

Objective: To evaluate the impact of bladder management method, specifically chronic indwelling catheter (IndC), on survival in patients with spinal cord injury (SCI) in Spinal Cord Injury Model System database., Methods: Spinal Cord Injury Model System is a multicenter longitudinal database since 1970 with >40,000 patients with SCI. Adult patients (>18 at the time of injury) were screened. Patients who died within 1 year of injury and had 2 or more changes in method of bladder management, or reported normal volitional void were excluded. Outcome of interest was death from nonpulmonary, nonwound related sepsis (NPNWS). Left truncation cox regression method using age as the time-scale was used to calculate hazard ratios., Results: A total of 13,616 patients were included. Comparison was performed between "IndC" group (n = 4872; 36.1%) vs "Other" (n = 8744; 63.9%). After adjusting for age and change in bladder management method, "IndC" is associated with elevated NPNWS mortality (2.10; 95% confidence interval 1.72-2.56, P < .001). Multivariable analysis, adjusting for age at injury, gender, race, education, insurance status, etiology of SCI, injury level, neurologic impairment level, and change in bladder management method, showed IndC was associated with significantly higher risk of death from NPNWS compared to other methods of bladder management., Conclusion: In a large cohort of SCI patients, bladder management with IndC is predictive of significantly propagated NPNWS related mortality compared to other methods of bladder management. While identifying IndC is an independent mortality risk factor, a better understanding of the underlying mechanisms could inform strategies to improve neurourological care and survival after SCI., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Optimal aminoglycoside dosing in critically ill patients represents a challenge for practitioners, especially in the medical intensive care unit (MICU). MICU patients exhibit altered pharmacokinetics due to pathophysiological changes the body undergoes in critical illness, leading to possible treatment failure. The literature surrounding optimal dosing and therapeutic drug monitoring strategies of aminoglycosides in MICU patients is scarce and conflicting. Additionally, only a few studies have investigated risk factors for suboptimal pharmacokinetic target obtainment. Currently, no definitive risk factors have been identified to predict suboptimal aminoglycoside target obtainment in MICU patients., Objective: The objective of this study was to determine risk factors for suboptimal pharmacokinetic target obtainment in patients receiving tobramycin in the MICU., Methods: This single-center, retrospective cohort study included patients 18-89 years old who received at least one 7 mg/kg tobramycin dose in the MICU from January, 1 2015 to September, 30 2020. Patients also had to have at least two detectable drug levels obtained at least one half-life apart following the first tobramycin dose. The primary outcome was to determine the incidence of optimal pharmacokinetic target obtainment, defined as a tobramycin maximum concentration (C max ) ≥ 10 mcg/ml, and to identify the risk factors for suboptimal (C max < 10 mcg/mL) pharmacokinetic target obtainment, in MICU patients. Secondary outcomes were compared between suboptimal and optimal target obtainment in patients with culture confirmed gram-negative infection susceptible to tobramycin. These secondary outcomes included all-cause in-hospital mortality, ICU length of stay (LOS), hospital LOS, and vasopressor duration in those with shock., Results: A total of 230 patients were included in this retrospective study. For the primary outcome, 187 (81.3%) patients achieved optimal target obtainment. Through multivariate logistic regression, female sex and serum albumin < 2.5 g/dL were identified as independent risk factors for suboptimal target obtainment; [OR = 2.14; 95% CI (1.05-4.37), p = 0.037], [OR = 2.50; 95% CI (1.21-5.19), p = 0.014], respectively. Fifty-four (23%) patients had culture-confirmed gram-negative infections susceptible to tobramycin and were included in the subgroup analysis. Of these 54 patients, 11 (20.4%) did not achieve optimal target concentrations. In patients with culture-confirmed gram-negative infection, there was no difference between patients with optimal target obtainment and suboptimal target obtainment in ICU LOS, hospital LOS, all-cause mortality, or vasopressor duration in those with shock., Conclusions: Among patients receiving their first dose of tobramycin in the MICU, 81.3% obtained an optimal serum concentration. Female sex and serum albumin < 2.5 g/dL were identified as risk factors for suboptimal target obtainment; however, further research is warranted to assess the utility of using these two covariates as risk factors for more aggressive dosing in critically ill MICU patients., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Neoadjuvant chemotherapy is the cornerstone treatment for locally advanced breast cancer. Balancing toxicity and efficacy are a common concern of patients treated with chemotherapy., Objective: The objective of this study was to determine the impact of dose intensity on pathologic complete response (pCR) at the time of surgery in patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer., Patients and Methods: A retrospective, single-center review was conducted on patients with HER2+ breast cancer who received neoadjuvant docetaxel, carboplatin, trastuzumab and pertuzumab (TCHP) followed by definitive surgery., Results: A total of 159 patients were included in the analysis; pCR was obtained in 66 patients (42%). There was no statistically significant difference between the mean dose intensity of each of the individual agents in TCHP and pCR rates. The mean overall dose intensity of docetaxel, carboplatin, trastuzumab and pertuzumab was 90.5%, 90.9%, 97.5%, and 93.9%, respectively. Although higher chemotherapy dose intensity (> 85%) was associated with higher pCR rates, no statistically significant difference was found compared with chemotherapy dose intensity < 85%. The TCHP regimen was difficult to tolerate; 104 patients (65%) required a dose reduction or dose delay during treatment due to toxicity., Conclusion: The TCHP regimen, which combines chemotherapy and HER2-directed therapy is effective at obtaining pCR in patients with locally advanced HER2+ breast cancer. These results suggest that the dose intensity of the individual agents did not have a significant impact on pCR rates. Given these findings, providers may be more comfortable allowing dose reductions for greater patient tolerability without sacrificing efficacy., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Cancer related pain is prevalent among patients with a cancer diagnosis, occurring from the tumor itself or as a result of treatment. Many patients require opioid therapy to manage pain and providers must balance efficacy with side effects. Transdermal buprenorphine (TDB) has shown promise for pain management, however, the maximum dose available in the US is considered low, resulting in doubts of efficacy. This study set out to assess if the patch strengths available in the US (5-20 mcg/hour) are able to provide analgesia for patients with cancer in a palliative medicine clinic. This retrospective chart review analyzed patient charts for outpatient TDB use within a palliative medicine clinic in the United States. Patients had to have a follow up visit with the clinic in order to be included. Sixty-eight patients were included for analysis with 54 (79%) continuing at least 28 days and 37 (54%) continuing for at least 84 days. The median change in pain score was 0, though 25 (46%) of patients reported a decrease of 1 or more points at the first follow up. TDB is a viable option for cancer related pain for select patients, demonstrated by duration of use and stable reporting of pain.

Background: Well-differentiated liposarcoma (WDLPS) is a low-grade soft tissue sarcoma with a propensity for local recurrence. The necessity of obtaining microscopically free surgical margins (R0) to minimize local recurrence is not clear. This study evaluates recurrence-free survival (RFS) of extremity WDLPS in relation to resection margin status., Methods: A retrospective review of adult patients with primary extremity WDLPS at seven US institutions from 2000 to 2016 was performed. Patients with recurrent tumors or incomplete resection (R2) were excluded. Clinicopathologic factors were analyzed to assess impact on local RFS., Results: 97 patients with primary extremity WDLPS were identified. The majority of patients had deep, lower extremity tumors. Mean tumor size was 18.2±8.9cm. Patients were treated with either radical (76.3%) or excisional (23.7%) resections; 64% had R0 and 36% had microscopically positive (R1) resection margins. Ten patients received radiation therapy with no difference in receipt of radiation between R0 vs R1 groups. Thirteen patients (13%) developed a local recurrence with no difference in RFS between R0 vs R1 resection. Five-year RFS was 59.5% for R0 vs 85.2% for R1. Only one patient died of disease after developing dedifferentiation and distant metastasis despite originally having an R0 resection., Discussion: In this large multi-institutional study of surgical resection of extremity WDLPS, microscopically positive margins were not associated with an increased risk of recurrence. Positive microscopic margin resection for extremity WDLPS may yield similar rates of local control while avoiding a radical approach to obtain microscopically negative margins.

Purpose: Adjuvant ovarian function suppression (OFS) in premenopausal hormone receptor (HR) positive breast cancer (BC) improves survival. Adherence to adjuvant gonadotropin-releasing hormone analogs (GnRHa) remains a challenge and is associated with toxicities and inconvenient parenteral administration. The goal of this study was to describe real-world adherence patterns and patient preferences surrounding adjuvant GnRHa., Methods: We analyzed the medical records of premenopausal women with non-metastatic HR positive BC from January 2000 to December 2017; participants received adjuvant monthly goserelin or leuprolide at The Ohio State University. Data collected included demographics, clinicopathologic characteristics, and OFS adherence/side effects. We defined non-adherence as discontinuation of GnRHa within 3 years for a reason other than switching to an alternate OFS, delay > 7 days from a dose, or a missed dose. Chi-square tests assessed associations between clinical characteristics and outcomes., Results: A total of 325 patients met eligibility. Of these, 119 (37%) patients were non-adherent to GnRHa; 137 (42%) underwent elective bilateral salpingo-oophorectomy after initial GnRHa. Those opting for surgery reported significantly more hot flashes (74% vs 48%, p < 0.001), arthralgias (46% vs 30%, p = 0.003), and vaginal dryness (37% vs 21%, p = 0.001) compared with patients remaining on GnRHa., Conclusion: Non-adherence to adjuvant GnRHa occurred in over a third of patients and almost half the patients initiating GnRHa underwent subsequent surgical ablation. These high frequencies highlight real-world patterns of OFS. Additionally, treatment toxicities may impact personal preference of OFS modality. Personalized practices to target predictors of adjuvant GnRHa non-adherence are critical to optimize symptoms, adherence, and survivorship., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Leptomeningeal carcinomatosis (LMC), a common complication of advanced malignancies, is associated with high morbidity and mortality, yet diagnosis and treatment decisions remain challenging. This study describes the diagnostic and treatment modalities for LMC and identifies factors associated with overall survival (OS)., Materials and Methods: We performed a single-institution retrospective study (registration #: OSU2016C0053) of 153 patients diagnosed with LMC treated at The Ohio State University, Comprehensive Cancer Center, (OSUCCC)-James between January 1, 2010 and December 31, 2015., Results: Median age at diagnosis was 55.7 years, and 61% had Eastern Cooperative Oncology Group baseline performance status ≤1. Most common primary tumors were breast (43%), lung (26%), and cutaneous melanoma (10%). At presentation, most patients were stage III-IV (71%) with higher grade tumors (grade III: 46%). Metastases to bone (36%), brain (33%), and lung (12%) were the most common sites with a median of 0.5 years (range, 0-14.9 years) between the diagnosis of first metastasis and of LMC. 153 (100%) patients had MRI evidence of LMC. Of the 67 (44%) who underwent lumbar puncture (LP), 33 (22%) had positive cerebrospinal fluid (CSF) cytology. Most patients received radiotherapy for LMC (60%) and chemotherapy (93%) for either the primary disease or LMC. 28 patients received intrathecal chemotherapy, 22 of whom had a primary diagnosis of breast cancer. 98% died with median OS of all patients was 1.9 months (95% CI: 1.3-2.5 months)., Conclusion: Despite improved treatments and targeted therapies, outcomes of LMC remain extremely poor. Positive CSF cytology was associated with lower OS in patients who had cytology assessed and specifically in patients with breast cancer. CSF cytology serves as an important indicator for prognosis and helps aid in developing individualized therapeutic strategies for patients with LMC., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (©Copyright 2021 by Turkish Federation of Breast Diseases Associations.)

Objective: To report the frequency of amyotrophic lateral sclerosis (ALS) genetic variants in a nationwide cohort of clinic-based patients with ALS with a family history of ALS (fALS), dementia (dALS), or both ALS and dementia (fALS/dALS)., Methods: A multicenter, prospective cohort of 573 patients with fALS, dALS, or fALS/dALS, underwent genetic testing in the ALS Genetic Access Program (ALS GAP), a clinical program for clinics of the Northeast ALS Consortium. Patients with dALS underwent C9orf72 hexanucleotide repeat expansion (HRE) testing; those with fALS or fALS/dALS underwent C9orf72 HRE testing, followed by sequencing of SOD1 , FUS , TARDBP , TBK1 , and VCP ., Results: A pathogenic (P) or likely pathogenic (LP) variant was identified in 171/573 (30%) of program participants. About half of patients with fALS or fALS/dALS (138/301, 45.8%) had either a C9orf72 HRE or a P or LP variant identified in SOD1 , FUS , TARDBP , TBK1 , or VCP . The use of a targeted, 5-gene sequencing panel resulted in far fewer uncertain test outcomes in familial cases compared with larger panels used in other in clinic-based cohorts. Among dALS cases 11.8% (32/270) were found to have the C9orf72 HRE. Patients of non-Caucasian geoancestry were less likely to test positive for the C9orf72 HRE, but were more likely to test positive on panel testing, compared with those of Caucasian ancestry., Conclusions: The ALS GAP program provided a genetic diagnosis to ∼1 in 3 participants and may serve as a model for clinical genetic testing in ALS., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Abstract: Anesthesiologists and surgeons have demonstrated a lack of familiarity with professional guidelines when providing care for surgical patients with a do-not-resuscitate (DNR) order. This substantially infringes on patient's self-autonomy; therefore, leading to substandard care particularly for palliative surgical procedures. The interventional nature of surgical procedures may create a different mentality of surgical "buy-in," that may unintentionally prioritize survivability over maintaining patient self-autonomy. While previous literature has demonstrated gains in communication skills with simulation training, no specific educational curriculum has been proposed to specifically address perioperative code status discussions. We designed a simulated standardized patient actor (SPA) encounter at the beginning of post-graduate year (PGY) 2, corresponding to the initiation of anesthesiology specific training, allowing residents to focus on the perioperative discussion in relation to the SPA's DNR order.Forty four anesthesiology residents volunteered to participate in the study. PGY-2 group (n = 17) completed an immediate post-intervention assessment, while PGY-3 group (n = 13) completed the assessment approximately 1 year after the educational initiative to ascertain retention. PGY-4 residents (n = 14) did not undergo any specific educational intervention on the topic, but were given the same assessment. The assessment consisted of an anonymized survey that examined familiarity with professional guidelines and hospital policies in relation to perioperative DNR orders. Subsequently, survey responses were compared between classes.Study participants that had not participated in the educational intervention reported a lack of prior formalized instruction on caring for intraoperative DNR patients. Second and third year residents outperformed senior residents in being aware of the professional guidelines that detail perioperative code status decision-making (47%, 62% vs 21%, P = .004). PGY-3 residents outperformed PGY-4 residents in correctly identifying a commonly held misconception that institutional policies allow for automatic perioperative DNR suspensions (85% vs 43%; P = .02). Residents from the PGY-3 class, who were 1 year removed the educational intervention while gaining 1 additional year of clinical anesthesiology training, consistently outperformed more senior residents who never received the intervention.Our training model for code-status training with anesthesiology residents showed significant gains. The best results were achieved when combining clinical experience with focused educational training., Competing Interests: The authors have no funding and conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Cataract surgery is the most common ambulatory surgery at our outpatient surgery center. Several studies have shown that patients with bilateral cataracts may experience different levels of anxiety, pain, and awareness during the first and second cataract extraction.A prospective observational cohort study was conducted at The Ohio State University Wexner Medical Center Eye and Ear Institute in order to compare anxiety, general comfort, awareness, and pain levels in patients undergoing sequential cataract surgeries. Likert and numerical rating scale were used to assess the outcomes. Patients receiving monitored anesthesia care and topical anesthesia were included.A total of 198 patients were enrolled in this study, 116 patients (59%) were female and 157 patients (78%) were Caucasians with a median age of 67 years among participants. Patients with rating "no anxiety" or feeling "somewhat anxious" were significantly higher during surgery 2 (P =< .001). Most of the patients felt "extremely comfortable" during surgery 1 when compared to surgery 2 (54% vs 42.9%; P = .08). No significant differences were found between surgeries regarding intraoperative awareness (P = .16). Overall, patients experienced mild pain during both procedures (92.4% in surgery 1 compared to 90.4% in surgery 2; P = .55). During the postoperative visit, 54% of the patients associated surgery 2 with less anxiety levels, 53% with no differences in general comfort, 60% felt more aware, and 59% had no differences in pain levels.Previous exposure to surgery could have been associated with a significant reduction in anxiety levels reported during surgery 2. Non-pharmacological strategies aiming to reduce perioperative anxiety may be considered an alternative or additional approach to premedication in patients undergoing consecutive cataract surgeries.

Objective: The use of endoscope-integrated indocyanine green (E-ICG) has recently been introduced in skull base surgery. The quantitative correlation between E-ICG and T1-weighted gadolinium-enhanced (T1WGd) images for skull base tumors has not been previously assessed, to the authors' knowledge. In this study, the authors investigated the indications for use and the limitations of E-ICG and sought to correlate the endoscopic fluorescence pattern with MRI contrast enhancement., Methods: Following IRB approval, 20 patients undergoing endoscopic endonasal skull base surgery between June 2017 and August 2018 were enrolled in the study. Tumor fluorescence was measured using a blue color value and blood fluorescence as a control. Signal intensities (SIs) of tumor T1WGd images were measured and the internal carotid artery (ICA) SI was used as a control. For pituitary adenoma, the pituitary gland fluorescence was also measured. The relationships between ICG fluorescence and MRI enhancement measurements were analyzed., Results: Data showed that in pituitary adenoma there was a strong correlation between the ratios of gland/blood fluorescence to gland/ICA SI (n = 8; r = 0.92; p = 0.001) and tumor/blood fluorescence to tumor/ICA SI (n = 9; r = 0.82; p = 0.006). In other pathologies there was a strong correlation between the ratios of tumor/blood fluorescence and tumor/ICA SI (n = 9; r = 0.74; p = 0.022). The ICG fluorescence allowed perfusion assessment of the pituitary gland as well as of the nasoseptal flaps. Visualization of the surrounding vasculature was also feasible., Conclusions: Defining the indications and understanding the limitations are critical for the effective use of E-ICG. Tumor fluorescence seems to correlate with preoperative MRI contrast enhancement.

Background: Simulation-based education (SBE) with high-fidelity simulation (HFS) offers medical students early exposure to the clinical environment, allowing development of clinical scenarios and management. We hypothesized that supplementation of standard pulmonary physiology curriculum with HFS would improve the performance of first-year medical students on written tests of pulmonary physiology., Methods: This observational pilot study included SBE with three HFS scenarios of patient care that highlighted basic pulmonary physiology. First-year medical students' test scores of their cardio-pulmonary curriculum were compared between students who participated in SBE versus only lecture-based education (LBE). A survey was administered to the SBE group to assess their perception of the HFS., Results: From a class of 188 first-year medical students, 89 (47%) participated in the SBE and the remaining 99 were considered as the LBE group. On their cardio-pulmonary curriculum test, the SBE group had a median score of 106 [IQR: 97,110] and LBE group of 99 [IQR: 89,105] (p < 0.001). For the pulmonary physiology subsection, scores were also significantly different between groups (p < 0.001)., Conclusions: Implementation of supplemental SBE could be an adequate technique to improve learning enhancement and overall satisfaction in preclinical medical students.

Background: Trastuzumab-induced cardiotoxicity (TIC) can lead to early discontinuation of adjuvant therapy, however there is limited evidence on long-term survival outcomes in patients with operable human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) experiencing treatment interruption or discontinuation., Methods: The primary objective of the study was to evaluate disease-free survival (DFS) in non-metastatic, HER2-positive, female BC patients who experienced treatment interruption or early discontinuation of trastuzumab therapy. Clinical and histopathological data were collected on 400 patients at The Ohio State University, an NCI-designated comprehensive cancer center between January 2005 and December 2015. Treatment interruption was defined as any delay of ≥2 weeks during trastuzumab therapy, including permanent cessation prior to completing planned therapy. TIC was defined as LVEF < 50% or > 15 points decline from baseline as evaluated by 2D echocardiogram after initiation of (neo) adjuvant therapy. DFS was defined as the time from diagnosis to first recurrence (loco-regional or distant recurrence) including second primary BC or death. Overall survival (OS) was defined as the time from diagnosis to death or last known follow up. OS/DFS estimates were generated using Kaplan-Meier methods and compared using Log-rank tests. Cox proportional hazard models were used to calculate adjusted hazard ratios (aHR) for OS/DFS., Results: A total of 369 patients received trastuzumab therapy; 106 (29%) patients experienced treatment interruption at least once and 42 (11%) permanently discontinued trastuzumab prior to completing planned therapy. TIC was the most common reason for interruption (66 patients, 62%). The median duration of trastuzumab in patients with treatment interruption was 11.3 months (range: 0.5-16.9) with 24 (23%) patients receiving ≤6 months of therapy. This duration includes the time delay related to treatment interruption. Patients with any treatment interruption had worse DFS (aHR: 4.4, p = 0.001) and OS (aHR: 4.8, p < 0.001) after adjusting for age, stage, grade, ER, node status and TIC., Conclusions: Treatment interruption or early discontinuation of trastuzumab therapy in early HER2-positive BC, most often from TIC, is an independent prognostic marker for worse DFS and OS in operable HER2-positive BC. Future prospective studies should consider targeting at-risk populations and optimizing cardiac function to avoid interruption in trastuzumab therapy.

Introduction: Renal colic secondary to kidney stone disease is a common reason for emergency department (ED) visits and often leads to patients receiving narcotic medications. The objective of this study was to describe longitudinal analgesia prescribing patterns for kidney stone patients acutely managed in the ED. Methods: This was a retrospective chart review of patients who presented to the ED between 2013 and 2018 and were subsequently diagnosed with a kidney stone. Encounters during which opioids and nonopioids were administered in the ED and prescribed at discharge were stratified by year, race, ethnicity, insurance status, gender, and location of ED (main academic campus and community-based campus). Patients were excluded if they required hospital admission or a stone-related procedure related to the ED encounter. Results: We reviewed 1620 total encounters for 1376 unique patients. Frequency of patients receiving opioids in the ED decreased from 81% in 2013 to 57% in 2018 ( p  < 0.001). During the same time period, nonopioid administration in the ED remained relatively unchanged (64% vs 67%). The proportion of patients prescribed opioids at discharge decreased from 77% to 59% ( p  < 0.001), while nonopioid prescriptions at discharge increased from 32% to 41% ( p  = 0.010). Frequency of administering both a narcotic and non-narcotic during the same ED encounter decreased over the 5-year period from 27% to 8% ( p  < 0.001). Conclusion: Opioids are being given less both during the ED encounter and at discharge for acute renal colic, while nonopioid prescribing is increasing. These trends may be due to increasing physician awareness to opioid addiction, or as a result of stricter legislation prohibiting opioid prescribing.

Purpose Capecitabine is widely used as a single agent on a 21-day cycle in the management of metastatic breast cancer (MBC). Our primary objective was to compare the standard dosing of capecitabine (Arm A: days 1-14 on 21-day cycle) to biweekly dosing (Arm B: days 1-7 and 15-21 on 28-day cycle) using retrospective data analysis. Methods 166 patients with MBC treated with single agent capecitabine at The Ohio State University from 2002 to 2014 were considered eligible. Median time to treatment failure (TTF) and overall survival (OS) were estimated using Kaplan-Meier (KM) methods. KM curves were compared using log-rank tests with Holm's correction for multiplicity. Results Patients were grouped by dose schedule into one of three arms: Arm A (21-day cycle; capecitabine given at 1000 mg/m 2 orally, twice daily on days 1-14 of 21-day cycle); Arm B (28-day cycle; capecitabine given at 1000 mg/m 2 orally, twice daily on days 1-7 and 15-21 of 28-day cycle); and Arm C (changeover regimen where patients started on the 21-day cycle, but changed to a 28-day cycle for tolerability). No difference was found in TTF or OS for patients with MBC between those who received capecitabine on either standard dosing (Arm A) and those on a biweekly cycle (Arm B or C). Overall, 41% of patients required dose reduction. Conclusions Our single institution experience showed that alternate dosing of capecitabine (biweekly, 28-day cycle) may be a reasonable alternative to standard 21-day cycle with similar efficacy and fewer dose reductions.

Background: Variants in TTN are frequently identified in the genetic evaluation of skeletal myopathy or cardiomyopathy. However, due to the high frequency of TTN variants in the general population, incomplete penetrance, and limited understanding of the spectrum of disease, interpretation of TTN variants is often difficult for laboratories and clinicians. Currently, cardiomyopathy is associated with heterozygous A-band TTN variants, whereas skeletal myopathy is largely associated with homozygous or compound heterozygous TTN variants. Recent reports show pathogenic variants in TTN may result in a broader phenotypic spectrum than previously recognized., Methods: Here we report the results of a multisite study that characterized the phenotypes of probands with variants in TTN. We investigated TTN genotype-phenotype correlations in probands with skeletal myopathy and/or cardiomyopathy. Probands with TTN truncating variants (TTNtv) or pathogenic missense variants were ascertained from two academic medical centers. Variants were identified via clinical genetic testing and reviewed according to the American College of Medical Genetics criteria. Clinical and family history data were documented via retrospective chart review. Family studies were performed for probands with atypical phenotypes., Results: Forty-nine probands were identified with TTNtv or pathogenic missense variants. Probands were classified by clinical presentation: cardiac (n = 30), skeletal muscle (n = 12), or both (cardioskeletal, n = 7). Within the cardioskeletal group, 5/7 probands had heterozygous TTNtv predicted to affect the distal (3') end of the A-band. All cardioskeletal probands had onset of proximal-predominant muscle weakness before diagnosis of cardiovascular disease, five pedigrees support dominant transmission., Conclusion: Although heterozygous TTNtv in the A-band is known to cause dilated cardiomyopathy, we present evidence that these variants may in some cases cause a novel, dominant skeletal myopathy with a limb-girdle pattern of weakness. These findings emphasize the importance of multidisciplinary care for patients with A-band TTNtv who may be at risk for multisystem disease., (© 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Objective: The primary objective of this study was to delineate differences in management, overall and distant disease-free survival in males diagnosed with breast cancer and treated at The Ohio State University Comprehensive Cancer Center as compared to comprehensively matched female subjects. Secondary objectives included assessment of clinical and histopathologic features and recurrence score, as measured by Oncotype DX and the modified Magee equation #2., Materials and Methods: This single institution retrospective study compared male and comprehensively matched female patients (1:2) with stage I-III breast cancer between 1994 and 2014. Recurrence risk was estimated using a modified Magee equation. Overall survival and distant disease-free survival were estimated and compared using Kaplan-Meier and Log-rank methods., Results: Forty-five male breast cancer patients were included (stage I: 26.7%; stage II: 53.3%; stage III: 20.0%; hormone receptor positive: 97.8%; human epidermal growth factor receptor 2 negative: 84.4%) with a median age of 63.8 (43.0-79.4) years at diagnosis. Intermediate and low recurrence scores were most common in male and female patients respectively; mean score was similar between groups (20.3 vs. 19.8). The proportion of male breast cancer patients treated with adjuvant chemotherapy and post-mastectomy radiation was lower compared to female patients (42.2% vs. 65.3%, p=0.013; 22.7% vs. 44.4%, p=0.030, respectively). Overall survival and distant disease-free survival between male and female patients were similar., Conclusion: Male breast cancer patient outcomes were similar compared to well-matched female patients suggesting that breast cancer specific factors are more prognostic than gender., Competing Interests: Conflict of Interest: The authors have no conflicts of interest to declare., (Copyright © 2020 Turkish Federation of Breast Diseases Associations.)

Background: Surgery on posterior cranial fossa (PCF) and pineal region (PR) carries the risks of intraoperative trauma to the brainstem structures, blood loss, venous air embolism (VAE), cardiovascular instability, and other complications. Success in surgery, among other factors, depends on selecting the optimal patient position. Our objective was to find associations between patient positioning, incidence of intraoperative complications, neurological recovery, and the extent of surgery. Methods: This observational study was conducted in two medical centers: The Ohio State University Wexner Medical Center (USA) and The Burdenko Neurosurgical Institute (Russian Federation). Patients were distributed in two groups based on the surgical position: sitting position (SP) or horizontal position (HP). The inclusion criteria were adult patients with space-occupying or vascular lesions requiring an open PCF or PR surgery. Perioperative variables were recorded and summarized using descriptive statistics. The post-treatment survival, functional outcome, and patient satisfaction were assessed at 3 months. Results: A total of 109 patients were included in the study: 53 in SP and 56 in HP. A higher proportion of patients in the HP patients had >300 mL intraoperative blood loss compared to the SP group (32 vs. 13%; p = 0.0250). Intraoperative VAE was diagnosed in 40% of SP patients vs. 0% in the HP group ( p < 0.0001). However, trans-esophageal echocardiographic (TEE) monitoring was more common in the SP group. Intraoperative hypotension was documented in 28% of SP patients compared to 9% in HP group ( p = 0.0126). A higher proportion of SP patients experienced a new neurological symptom compared to the HP group (49 vs. 29%; p = 0.0281). The extent of tumor resection, postoperative 3-months survival, functional outcome, and patient satisfaction were not different in the groups. Conclusions: The SP was associated with, less intraoperative bleeding, increased intraoperative hypotension, VAE, and postoperative neurological deficit. More HP patients experienced macroglossia and increased blood loss. At 3 months, there was no difference of parameters between the two groups. Clinical Trial Registration: ClinicalTrials.gov: registration number NCT03364283., (Copyright © 2020 Mavarez-Martinez, Israelyan, Soghomonyan, Fiorda-Diaz, Sandhu, Shimansky, Ammirati, Palettas, Lubnin and Bergese.)

Background: Metaplastic breast cancer remains poorly characterized given its rarity and heterogeneity. The majority of metaplastic breast cancers demonstrate a phenotype of triple-negative breast cancer; however, differences in clinical outcomes between metaplastic breast cancer and triple-negative breast cancer in the era of third-generation chemotherapy remain unclear., Methods: We compared the clinical outcomes between women with metaplastic breast cancer and women with triple-negative breast cancer diagnosed between 1994 and 2014. Metaplastic breast cancer patients were matched 1:3 to triple-negative breast cancer patients by stage and age at diagnosis. Distant disease-free survival (DDFS) and overall survival (OS) were estimated using Kaplan Meier methods and Cox proportional hazard regression models. Immune checkpoint markers were characterized by immunohistochemistry in a subset of samples., Results: Forty-four metaplastic breast cancer patients (stage I 14%; stage II 73%; stage III 11%; stage IV 2%) with an average age of 55.4 (± 13.9) years at diagnosis. Median follow-up for the included metaplastic breast cancer and triple-negative breast cancer patients (n = 174) was 2.8 (0.1-19.0) years. The DDFS and OS between matched metaplastic breast cancer and triple-negative breast cancer patients were similar, even when adjusting for clinical covariates (DDFS: HR = 1.64, p = 0.22; OS: HR = 1.64, p = 0.26). Metaplastic breast cancer samples (n = 27) demonstrated greater amount of CD163 in the stroma (p = 0.05) and PD-L1 in the tumor (p = 0.01) than triple-negative breast cancer samples (n = 119), although more triple-negative breast cancer samples were positive for CD8 in the tumor than metaplastic breast cancer samples (p = 0.02)., Conclusions: Patients with metaplastic breast cancer had similar outcomes to those with triple-negative breast cancer based on DDFS and OS. The immune checkpoint marker profile of metaplastic breast cancers in this study may prove useful in future studies attempting to demonstrate an association between immune profile and survival.

Objective: To determine the incidence of amyotrophic lateral sclerosis (ALS) genetic variants in a clinic-based population., Methods: A prospective cohort of patients with definite or probable ALS was offered genetic testing using a testing algorithm based on family history and age at onset., Results: The incidence of pathogenic (P) or likely pathogenic (LP) variants was 56.0% in familial ALS (fALS); 11.8% in patients with ALS with a family history of dementia, and 6.8% in sporadic ALS ( p < 0.001). C9orf72 expansions accounted for the majority (79%) of P or LP variants in fALS cases. Variants of uncertain significance were identified in 20.0% of fALS cases overall and in 35.7% of C9orf72 -negative cases. P or LP variants were detected in 18.5% of early-onset cases (onset age <50 years); the incidence of P or LP variants was not significantly different between family history types in this group., Conclusions: Our data suggest that the incidence of P and LP variants in genes other than C9orf72 is lower than expected in Midwestern fALS cases compared with research cohorts and highlights the challenge of variant interpretation in ALS. An accurate understanding of the incidence of pathogenic variants in clinic-based ALS populations is necessary to prioritize targets for therapeutic intervention and inform clinical trial design., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Perioperative hypertension is a common occurrence in the neurosurgical population, where 60% to 90% of the patients require treatment for blood pressure (BP) control. Nicardipine and clevidipine have been commonly used in neurocritical settings. This retrospective, observational study assessed the effectivity of the administration of clevidipine after nicardipine treatment failure in neurosurgical patients.We retrospectively reviewed the medical charts of adult patients who were admitted to our neurosurgical department and received clevidipine after nicardipine treatment failure for the control of BP. The primary effectivity outcome was the comparison of the percentage of time spent at targeted SBP goals during nicardipine and clevidipine administration, respectively.A total of 12 adult patients treated with clevidipine after nicardipine treatment failure and were included for data analysis. The median number of events that required dose-titration was 20.5 vs 17 during the administration of nicardipine and clevidipine, respectively (P = .534). The median percentage of time spent at targeted SBP goal was 76.2% during the administration of nicardipine and 93.4% during the administration of clevidipine (P = .123).Our study suggests that clevidipine could be an alternative effective drug with an acceptable benefit/risk ratio in the neurosurgical population that fails to achieve BP control with nicardipine treatment.

Background: Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia/lymphoma (ATL) and the neurological disorder HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The exact mechanism(s) through which latency and disease progression are regulated are not fully understood. CCCTC-binding factor (CTCF) is an 11-zinc finger, sequence-specific, DNA-binding protein with thousands of binding sites throughout mammalian genomes. CTCF has been shown to play a role in organization of higher-order chromatin structure, gene expression, genomic imprinting, and serve as a barrier to epigenetic modification. A viral CTCF-binding site (vCTCF-BS) was previously identified within the overlapping p12 (sense) and Hbz (antisense) genes of the HTLV-1 genome. Thus, upon integration, HTLV-1 randomly inserts a vCTCF-BS into the host genome. vCTCF-BS studies to date have focused primarily on HTLV-1 chronically infected or tumor-derived cell lines. In these studies, HTLV-1 was shown to alter the structure and transcription of the surrounding host chromatin through the newly inserted vCTCF-BS. However, the effects of CTCF binding in the early stages of HTLV-1 infection remains unexplored. This study examines the effects of the vCTCF-BS on HTLV-1-induced in vitro immortalization and in vivo viral persistence in infected rabbits., Results: HTLV-1 and HTLV-1∆CTCF LTR-transactivation, viral particle production, and immortalization capacity were comparable in vitro. The total lymphocyte count, proviral load, and Hbz gene expression were not significantly different between HTLV-1 and HTLV-1∆CTCF-infected rabbits throughout a 12 week study. However, HTLV-1∆CTCF-infected rabbits displayed a significantly decreased HTLV-1-specific antibody response compared to HTLV-1-infected rabbits., Conclusions: Mutation of the HTLV-1 vCTCF-BS does not significantly alter T-lymphocyte transformation capacity or early in vivo virus persistence, but results in a decreased HTLV-1-specific antibody response during early infection in rabbits. Ultimately, understanding epigenetic regulation of HTLV-1 gene expression and pathogenesis could provide meaningful insights into mechanisms of immune evasion and novel therapeutic targets.