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Purpose Hydralazine, doxazosin, and verapamil are currently recommended by the Endocrine Society as acceptable bridging treatment in those in whom full cessation of antihypertensive medication is infeasible during screening for primary aldosteronism (PA). This is under the assumption that they cause minimal to no effect on the aldosterone-to-renin ratio, the most widely used screening test for PA. However, limited evidence is available regarding the effects of these particular drugs on said ratio. Methods In the present study, we retrospectively assessed the changes in aldosterone, renin, and aldosterone-to-renin values in essential hypertensive participants before and after treatment with either hydralazine (n = 26) or doxazosin (n = 20) or verapamil (n = 15). All samples were taken under highly standardized conditions. Results Hydralazine resulted in a borderline significant rise in active plasma renin concentration (19 vs 25 mIU/L, p = 0.067) and a significant fall in the aldosterone-to-renin ratio (38 vs 24, p = 0.017). Doxazosin caused declines in both plasma aldosterone concentration (470 vs 330 pmol/L, p = 0.028) and the aldosterone-to-renin ratio (30 vs 20, p = 0.020). With respect to verapamil, we found no statistically significant effect on any of these outcome variables. Conclusion We conclude that the assumption that these drugs can be used with little consequence to the aldosterone-to-renin cannot be substantiated. While it is possible that they are indeed the best option when full antihypertensive drug cessation is infeasible, the potential effects of these drugs must still be taken into account when interpreting the aldosterone-to-renin ratio.

Background Mortality for infants on the heart transplant wait list remains unacceptably high, and available mechanical circulatory support is suboptimal. Our goal is to demonstrate the feasibility of utilizing genetically engineered pig (GEP) heart as a bridge to allotransplantation by transplantation of a GEP heart in a baboon. Methods Four baboons underwent orthotopic cardiac transplantation from GEP donors. All donor pigs had galactosyl-1,3-galactose knocked out. Two donor pigs had human complement regulatory CD55 transgene and the other 2 had human complement regulatory CD46 and thrombomodulin. Induction immunosuppression included thymoglobulin, and Anti-CD20. Maintenance immunosuppression was Rapamycin, AntiCD-40 and methylprednisolone. One donor heart was preserved with University of Wisconsin (UW) solution and the other three with del Nido solution. Results All baboons weaned from cardiopulmonary bypass. B217 received a donor heart preserved with UW. Ventricular arrhythmias and depressed cardiac function resulted in early death. All recipients of del Nido preserved hearts easily weaned from cardiopulmonary bypass with minimal inotropic support. B15416 and B1917 survived for 90 days and 241 days respectively. Histopathology in B15416 revealed no significant myocardial rejection but cellular infiltrate around Purkinje fibers. Histopathology in B1917 was consistent with severe rejection. B37367 had uneventful transplant but developed significant respiratory distress with a cardiac arrest. Conclusions Survival of B15416 and B1917 demonstrates the feasibility of pursuing additional research to document the ability to bridge an infant to cardiac allotransplant with a GEP heart.

IMPORTANCE: This study identifies the diagnostic errors leading to misdiagnosis of 3(rd) nerve palsy in order to aid clinicians in making this diagnosis. OBJECTIVE: To determine the incidence of misdiagnosis of third cranial nerve palsy (3(rd) nerve palsy) amongst providers referring to a tertiary care neuro-ophthalmology clinic and to characterize diagnostic errors that led to an incorrect diagnosis. DESIGN: Retrospective clinic-based cross-sectional study of office encounters at two institutions from 1/2014 to 1/2017. All encounters with scheduling comments containing variations of “3(rd) nerve palsy” were reviewed. Patients with a documented referral diagnosis of new 3(rd) neve palsy were included in the study. Examination findings including extraocular movement exam, external lid exam, and pupil exam were collected. The final diagnosis was determined by a neuro-ophthalmologist. The Diagnosis Error Evaluation and Research (DEER) taxonomy tool was used to categorize the causes of misdiagnosis. SETTING: Multicenter study describing patients at two neuro-ophthalmology referral centers. PARTICIPANTS: 78 patients referred for a new diagnosis of 3(rd) nerve palsy. MAIN OUTCOMES AND MEASURES: The main outcome measure was the type of diagnostic error that led to incorrect diagnoses using the DEER criteria as determined by two independent reviewers. Secondary outcomes were rates of misdiagnosis, misdiagnosis rate by referring specialty, and examination findings associated with incorrect diagnoses. RESULTS: Out of 78 patients referred with a suspected diagnosis of 3(rd) nerve palsy, 21.8% were determined to have an alternate diagnosis. The most common error in misdiagnosed cases was failure to correctly interpret the physical exam. Ophthalmologists were the most common referring provider for third nerve palsy, and optometrists had the highest overdiagnosis rate of 3(rd) nerve palsy. CONCLUSIONS: Misdiagnosis of 3(rd) nerve palsy was common. Performance and interpretation of the physical exam were the most common factors leading to misdiagnosis of 3(rd) nerve palsy.

Background Hybrid Closed Loop (HCL) systems aid individuals with type 1 diabetes in improving glycemic control, however, sustained use over time has not been consistent for all users. This study developed and validated prognostic models for successful 12-month use of the first commercial HCL system based on baseline and 1-month or 3-month data. Methods and materials Data from participants at the Barbara Davis Center (N=85) who began use of the MiniMed 670G HCL were used to develop prognostic models using logistic regression and Lasso model selection. Candidate factors included sex, age, duration of diabetes, baseline HbA1c, race, ethnicity, insurance status, history of insulin pump and continuous glucose monitor use, 1-month or 3-month Auto Mode use, boluses per day, and time in range (70-180 mg/dL; TIR), and scores on behavioral questionnaires. Successful use of HCL was predefined as Auto Mode use ≥60%. The 3-month model was then externally validated against a sample from Stanford University (N=55). Results Factors in the final model included baseline HbA1c, sex, ethnicity, 1-month or 3-month Auto Mode use, Boluses per Day, and TIR. The 1-month and 3-month prognostic models had very good predictive ability with area under the curve values of 0.894 and 0.900, respectively. External validity was acceptable with an area under the curve of 0.717. Conclusions Our prognostic models use clinically accessible baseline and early device-use factors to identify risk for failure to succeed with 670G HCL technology. These models may be useful to develop targeted interventions to promote success with new technologies.

The transition from inpatient to outpatient shoulder arthroplasty critically depends on appropriate patient selection, both to ensure safety and to counsel patients preoperatively regarding individualized risk. Cost and patient demand for same-day discharge have encouraged this transition, and a validated predictive tool may help decrease surgeon liability for complications and help select patients appropriate for same-day discharge. We hypothesized that an accurate predictive model could be created for short inpatient length of stay (discharge at least by postoperative day 1), potentially serving as a useful proxy for identifying patients appropriate for true outpatient shoulder arthroplasty.A multicenter cohort of 5410 shoulder arthroplasties (2805 anatomic and 2605 reverse shoulder arthroplasties) from 2 geographically diverse, high-volume health systems was reviewed. Short inpatient stay was the primary outcome, defined as discharge on either postoperative day 0 or 1, and 49 patient outcomes and factors including the Elixhauser Comorbidity Index, sociodemographic factors, and intraoperative parameters were examined as candidate predictors for a short stay. Factors surviving parameter selection were incorporated into a multivariable logistic regression model, which underwent internal validation using 10,000 bootstrapped samples.In total, 2238 patients (41.4%) were discharged at least by postoperative day 1, with no difference in rates of 90-day readmission (3.5% vs. 3.3%, P = .774) between cohorts with a short length of stay and an extended length of stay (discharge after postoperative day 1). A multivariable logistic regression model demonstrated high accuracy (area under the receiver operator characteristic curve, 0.762) for discharge by postoperative day 1 and was composed of 13 variables: surgery duration, age, sex, electrolyte disorder, marital status, American Society of Anesthesiologists score, paralysis, diabetes, neurologic disease, peripheral vascular disease, pulmonary circulation disease, cardiac arrhythmia, and coagulation deficiency. The percentage cutoff maximizing sensitivity and specificity was calculated to be 47%. Internal validation showed minimal loss of accuracy after bias correction for overfitting, and the predictive model was incorporated into a freely available online tool to facilitate easy clinical use.A risk prediction tool for short inpatient length of stay after shoulder arthroplasty reaches very good accuracy despite requiring only 13 variables and was derived from an underlying database with broad geographic diversity in the largest institutional shoulder arthroplasty cohort published to date. Short inpatient length of stay may serve as a proxy for identifying patients appropriate for same-day discharge, although perioperative care decisions should always be made on an individualized and holistic basis.

Anatomic total shoulder arthroplasty (TSA) and reverse TSA are the standard of care for end-stage shoulder arthritis. Advancements in implant design, perioperative management, and patient selection have allowed shorter inpatient admissions. Unplanned readmissions remain a significant complication. Identification of risk factors for readmission is prudent as physicians and payers prepare for the adoption of bundled care reimbursement models. The purpose of this study was to identify characteristics and risk factors associated with readmission following shoulder arthroplasty using a large, bi-institutional cohort.A total of 2805 anatomic TSAs and 2605 reverse TSAs drawn from 2 geographically diverse, tertiary health systems were examined for unplanned inpatient readmissions within 90 days following the index operation (primary outcome). Forty preoperative patient sociodemographic and comorbidity factors were tested for their significance using both univariable and multivariable logistic regression models, and backward stepwise elimination selected for the most important associations for 90-day readmission. Readmissions were characterized as either medical or surgical, and subgroup analysis was performed. A short length of stay (discharge by postoperative day 1) and discharge to a rehabilitation or skilled nursing facility were also examined as secondary outcomes. Parameters associated with increased readmission risk were included in a predictive model.Within 90 days of surgery, 175 patients (3.2%) experienced an unanticipated readmission, with no significant difference between institutions (P = .447). There were more readmissions for surgical complications than for medical complications (62.9% vs. 37.1%, P.001). Patients discharged to a rehabilitation or skilled nursing facility were significantly more likely to be readmitted (13.1% vs. 8.8%, P = .049), but a short inpatient length of stay was not associated with an increased rate of 90-day readmission (42.9% vs. 41.3%, P = .684). Parameter selection based on predictive ability resulted in a multivariable logistic regression model composed of 16 preoperative patient factors, including reverse TSA, revision surgery, right-sided surgery, and various comorbidities. The area under the receiver operator characteristic curve for this multivariable logistic regression model was 0.716.Risk factors for unplanned 90-day readmission following shoulder arthroplasty include reverse shoulder arthroplasty, surgery for revision and fracture, and right-sided surgery. Additionally, there are several modifiable and nonmodifiable risk factors that can be used to ascertain a patient's readmission probability. A shorter inpatient stay is not associated with an increased risk of readmission, whereas discharge to post-acute care facilities does impose a greater risk of readmission. As scrutiny around health care cost increases, identifying and addressing risk factors for readmission following shoulder arthroplasty will become increasingly important.

Objective: To describe real-world outcomes for youth using the Tandem t:slim X2 insulin pump with Control-IQ technology (“Control-IQ”) for 6 months at a large pediatric clinic. Methods: Youth with type 1 diabetes, who started Control-IQ for routine care, were prospectively followed. Data on system use and glycemic control were collected before Control-IQ start, and at 1, 3, and 6 months after start. Mixed models assessed change across time; interactions with baseline hemoglobin A1c (HbA1c) and age were tested. Results: In 191 youth (median age 14, 47% female, and median HbA1c 7.6%), percent time with glucose levels 70–180 mg/dL (time-in-range [TIR]) improved from 57% at baseline to 66% at 6 months (P 70%) doubled from 23.5% at baseline to 47.8% at 3 months, sustaining at 46.7% at 6 months (P

Objective To evaluate if decreasing postop abx prophylaxis affects UTI and wound infection rates in patients following urethroplasty. Methods A retrospective review of patients who underwent urethroplasty from 9/2017 - 3/2020 by a single surgeon was performed. All patients received urine culture specific perioperative IV abx prior to urethroplasty and kept a urethral catheter for 3 weeks postop. Patients undergoing a urethroplasty from 9/2017 to 12/2018 received extended postop abx prophylaxis for 3 weeks until catheter removal (Group 1). Patients from 12/2018 to 3/2020 received abx for 3 days around catheter removal (Group 2). UTIs, abx complications, and wound infections between groups were evaluated. UTIs were defined as a positive urine culture or reported lower urinary tract symptoms/fevers treated with empiric abx. Results 120 patients underwent urethroplasty. Group 1 consisted of 60 patients with mean age of 51.9 years and mean stricture length of 3.6 cm. Group 2 had 60 patients with mean age of 53.1 years and mean stricture length of 3.8 cm. 10 patients had UTIs after urethroplasty. There was no significant difference in UTI (6.7% vs 11.7%; P = 0.529) or wound infection rates (3.3% vs 1.7%;’ P = 1.000) between the two groups. Conclusion Extended postoperative antibiotic prophylaxis does not appear to significantly affect UTI or wound infection rates following urethroplasty. The retrospective nature of the study has limitations, however, this is the first comparison of two different antibiotic administration protocols to our knowledge.

Purpose To establish an infection rate following primary arthroscopic rotator cuff repair (ARCR) from a single institutional database and to ascertain whether there is a relationship between the use of preoperative corticosteroid injection (CSI) and the risk of postoperative infection. Methods All medical records at a single institution were retrospectively reviewed to identify patients who had undergone arthroscopic repair from January 2016 to December 2018. Patient charts were reviewed for CSI treatment within 6 months of surgery, superficial or deep infection within 2 months postoperatively, and specific treatment of the infection. Patient characteristics were summarized by descriptive statistics using means with standard deviations for continuous variables and frequencies with percentages for categorical variables. A χ2 correlation analysis was performed to determine the association between receiving an injection and having an infection. Results A total of 1773 patients were included for analysis with an average age of 59.24 ± 9.4 years. The overall infection rate was 0.11% (2/1773 patients). Both patients were treated with oral antibiotics. Of the included patients, 616 had a preoperative CSI within 6 months of their surgery, and 102 injections were administered within 1 month of surgery. None of these patients had a postoperative infection. A χ2 correlation analysis showed a negligible relationship between preoperative injections and postoperative infection (φ = 0.02, χ2 = 0.84). Conclusions Through this single-institution, large cohort retrospective review, we found an overall 0.11% rate of postoperative infection following primary arthroscopic RCR. In addition, we found no correlation between the use of preoperative CSI ahead of elective ARCR at any time point and risk of developing a postoperative infection. Infection is uncommon following ARCR, and preoperative steroid injection did not increase infection risk in our study population. Level of Evidence Level IV, therapeutic case series.

OBJECTIVE To evaluate the safety of 3 Tesla (T) magnetic resonance imaging (MRI) in patients with auditory brainstem implants (ABI) with the magnet removed at implantation and report incidence of complications. STUDY DESIGN Retrospective chart review. SETTING Tertiary neurotology ambulatory practice. PATIENTS Patients with diagnosis of Neurofibromatosis, type 2 (NF2) with functional ABIs. INTERVENTIONS Observational recordings. MAIN OUTCOME MEASURES Of the 89 patients meeting inclusion criteria, 7 patients underwent 3T MRI, with a total of 39 scans done. Three patients had 1 scan each, one patient had 4 scans, one patient had 5 scans, one patient had 6 scans, and one patient had 21 scans. The mean time between ABI placement and first 3 T scan was 118 ± 73 months. The most common indication for imaging was surveillance of NF2 lesions. The most frequent scans were MRI brain (25.6%), followed by MRI of cervical (15%), thoracic (15%) and lumbar (15%) spine, and MRI IAC (8%). There were no reported complications for any of the scans. No scans were interrupted due to patient discomfort. There were no device malfunctions. CONCLUSIONS 3 T MRIs are safe in patients with ABIs as long as the magnet is removed. It is recommended that the magnet be removed at the time of implantation in all NF2 patients, who require frequent surveillance.

Objective To investigate the utility of the so-called "second window" of indocyanine green (ICG) as a near-infrared fluorescent dye for intraoperative visualization. Patients Three patients who underwent surgical resection of vestibular schwannoma (two retrosigmoid and one middle fossa approach). Interventions Patients underwent intravenous infusion of ICG at a mean dose of 4.8 mg/kg at a mean of 15.3 hours before surgical incision. Once tumor dissection began, near-infrared fluorescence was used alongside conventional operative microscopy to visualize tumor tissue. Main outcome measures Ability to distinguish tumor tissue from adjacent nerves. Results Intraoperative fluorescence allowed for enhanced visualization of the tumor-nerve plane in all patients. However, the effect varied among patients, and the effect faded with increasing surgical time. Conclusions ICG, a well-tolerated cyanine dye, demonstrates late fluorescence hours after administration secondary to diffusion into tumor as well as normal tissues (the so-called "second window" of fluorescence). Its fluorescence in the near-infrared spectrum is a promising adjunct for enhancing visualization of tumor planes during vestibular schwannoma surgery.

Numerous studies have demonstrated the clinical value and safety of insulin pump therapy in type 1 diabetes and type 2 diabetes populations. However, the eligibility criteria for insulin pump coverage required by the Centers for Medicare & Medicaid Services (CMS) discount conclusive evidence that supports insulin pump use in diabetes populations that are currently deemed ineligible. This article discusses the limitations and inconsistencies of the insulin pump eligibility criteria relative to current scientific evidence and proposes workable solutions to address this issue and improve the safety and care of all individuals with diabetes.

Since its introduction, the Patient-Reported Outcomes Measurement Information System Upper Extremity (PROMIS UE) assessment has been increasingly used in shoulder arthroplasty outcome measurement. However, determination of clinically significant outcomes using the PROMIS UE has yet to be investigated following reverse total shoulder arthroplasty (RTSA). We hypothesized that we could establish clinically significant outcomes of the PROMIS UE outcome assessment in patients undergoing primary RTSA and identify significant baseline patient factors associated with achievement of these measures.Consecutive patients undergoing primary RTSA between 2018 and 2019 who received preoperative baseline and follow-up PROMIS UE assessments at 12 months after surgery were retrospectively reviewed. Domain-specific anchor questions pertaining to pain and function assessed at 12 months after surgery were used to determine minimal clinically important difference (MCID), substantial clinical benefit (SCB), and patient acceptable symptomatic state (PASS) values for the PROMIS UE using receiver operating characteristic curve and area-under-the-curve (AUC) analysis. Univariate logistic regression analysis was then performed to identify significant patient factors associated with achieving the MCID, SCB, or PASS.A total of 95 patients met all inclusion criteria and were included in the analysis. By use of an anchor-based method, the PASS value was 36.68 (sensitivity, 0.795; specificity, 0.765; AUC, 0.793) and the SCB value was 11.62 (sensitivity, 0.597; specificity, 1.00; AUC, 0.806). By use of a distribution-based method, the MCID value was calculated to be 4.27. Higher preoperative PROMIS UE scores were a positive predictor in achievement of the PASS (odds ratio [OR], 1.107; P = .05), whereas lower preoperative PROMIS UE scores were associated with obtaining SCB (OR, 0.787; P.001). Greater baseline forward flexion was negatively associated with achievement of the PASS (OR, 0.986; P = .033) and MCID (OR, 0.976, P = .013). Of the patients, 83.2%, 69.5%, and 47.4% achieved the MCID, PASS, and SCB, respectively.This study defines the MCID, SCB, and PASS for the PROMIS UE outcome assessment in patients undergoing primary RTSA, of whom the majority achieved meaningful outcome improvement at 12 months after surgery. These values may be used in assessing the outcomes and extent of functional improvement following RTSA.

Purpose: Typical doses of 45–50.4 Gy used to treat regional nodes have demonstrated inadequate control of gross nodal disease (GND) in gynecologic cancer, and accelerated repopulation may limit the efficacy of a sequential boost. We reviewed outcomes of patients treated with a simultaneous integrated boost (SIB) at 2.25 Gy per fraction to positron emission tomography (PET) avid GND to evaluate toxicity and tumor control using this dose-escalated regimen.Materials and Methods: A total of 83 patients with gynecologic cancer and PET avid inguinal, pelvic, or para-aortic lymphadenopathy were treated using intensity-modulated radiation therapy (IMRT) with SIB. Primary cancers were mostly cervical (51%) and endometrial (34%), and included patients who received concurrent chemotherapy (59%) and/or brachytherapy boost (78%).Results: Median follow-up from radiation completion was 12.6 months (range, 2.7 to 92.9 months). Median dose to elective lymphatics was 50.4 Gy (range, 45 to 50.4 Gy) at 1.8 Gy/fraction. Median SIB dose and volume were 63 Gy (range, 56.3 to 63 Gy) and 72.8 mL (range, 6.8 to 1,134 mL) at 2–2.25 Gy/fraction. Nodal control was 97.6% in the SIB area while 90.4% in the low dose area (p = 0.013). SIB radiotherapy (RT) field failure-free, non-SIB RT field failure-free, and out of RT field failure-free survival at 4 years were 98%, 86%, and 51%, respectively. Acute and late grade ≥3 genitourinary toxicity rates were 0%. Acute and late grade ≥3 gastrointestinal toxicity rates were 7.2% and 12.0%, respectively.Conclusion: Dose escalated SIB to PET avid adenopathy results in excellent local control with acceptable toxicity.

Background Neurologic injury after shoulder arthroplasty has been reported in previous outcome studies. However, the incidence and development of distal peripheral neuropathy (DPN) after shoulder arthroplasty requiring surgical intervention has not been previously described. Hypothesis The authors report on the incidence of DPN requiring surgical intervention following shoulder arthroplasty. Methods A retrospective review was conducted of a prospectively collected shoulder arthroplasty registry at a single institution from a single surgeon from April 2006 to April 2017. Patients were included in the series if they had primary surgical intervention for ipsilateral or contralateral peripheral neuropathy following primary shoulder arthroplasty. Patients were excluded if they had known peripheral neuropathy or cervical radiculopathy prior to surgery. DPN was defined for the study as symptoms or diagnostic testing consistent with cubital tunnel or carpal tunnel syndrome. Demographics, patient reported outcome measures, and preoperative and postoperative shoulder range of motion were collected and analyzed with paired t-tests and multivariate regression models. Results One thousand three hundred eighty-seven total shoulder arthroplasties were performed in this period. During the study period, 16 patients (1.2%) underwent surgery for ipsilateral DPN while 6 patients (0.4%) underwent surgery for contralateral DPN. ASES scores, SANE scores, and shoulder flexion improved significantly from pre- to postoperatively for both groups. There was no significant difference in postoperative scores between groups. Finally, the multivariate linear analysis did not yield any statistically significant regression equations for ASES, SANE VAS, AFE, and AER. Conclusion Shoulder arthroplasty resulted in increased ipsilateral distal peripheral neuropathy. Emergence of DPN symptoms following arthroplasty is multifactorial and may be related to a form of the double crush syndrome. Level of evidence Level IV; Case series

Background Primary small cell carcinoma of the pancreas (SCCP) is a rare malignant neuroendocrine carcinoma (NEC). Typically, it presents with lymphovascular invasion as well as metastasis at the time of diagnosis which portends a dismal prognosis. Treatment is typically based on therapy used for other aggressive NECs such as small cell lung cancer. Although multimodal surgery, radiation and chemotherapy may improve prognosis, the outcome generally remains poor. Case presentation Here we present a primary SCCP managed with neoadjuvant multi-agent chemotherapy combined with radiotherapy and surgery Conclusions Multi-disciplinary therapy resulted in an ongoing 28 + month radiographic complete response and overall survival.

Arthrodesis of the hindfoot is typically used for the correction of severe and arthritic progressive collapsing foot deformity. Concomitant bony or soft tissue procedures may be helpful in patients with congenital abnormalities including the ball-and-socket ankle or congenital vertical talus. Dysplasia of the hindfoot bones may be more common than previously recognized, and corrective procedures or alterations in technique may need to be performed during hindfoot arthrodesis to account for bony deformity. Intraarticular osteotomies, extraarticular osteotomies, tendon lengthening, and tendon transfer procedures may be used in specific instances to aid in deformity correction and improve overall function.

Objective Suicide is a leading cause of death in children and adolescents, and healthcare encounters relating to suicidal ideation (SI) and suicide attempt (SA) are steadily increasing. Studies examining healthcare utilization by adolescents prior to emergency department (ED) evaluation for SI/SA are lacking and may guide risk assessment. Methods We performed a descriptive study of patients 10 to 18 years evaluated for SI/SA in either of our 2 academic, pediatric EDs between January 1 and December 31, 2016. We quantified and characterized healthcare encounters in the year preceding ED evaluation for SI/SA by obtaining data from the electronic health record. Results We identified 599 patients with an index ED visit for evaluation of SI/SA. Mean age was 14.1 years (SD 2.0 years); 69.8% female, 61.9% White, 55.4% publicly insured. Fifty-six percent (336/599) had at least one previous encounter within our healthcare system in the year preceding their index ED visit (median 3, maximum 40, IQR: 2, 7), most commonly among Black/African American and Hispanic adolescents. Among all patients we identified 1409 previous encounters, and 55.4% (780/1409) occurred within 6 months of the index ED visit. Sixty-two percent (880/1409) of previous encounters were to an outpatient clinic, primarily nonmental health, subspecialty clinics. Conclusions Adolescent healthcare encounters in the year preceding ED evaluation for SI/SA occur in a variety of settings. A broad approach to suicide risk screening may improve opportunities for early identification and intervention.

BACKGROUND Isolated third nerve palsy may indicate an expanding posterior communicating artery aneurysm, thus necessitating urgent arterial imaging. This study aims to assess the rate and duration of delays in arterial imaging for new isolated third nerve palsies, identify potential causes of delay, and evaluate instances of delay-related patient harm. METHODS In this cross-sectional study, we retrospectively reviewed 110 patient charts (aged 18 years and older) seen between November 2012 and June 2020 at the neuro-ophthalmology clinic and by the inpatient ophthalmology consultation service at a tertiary institution. All patients were referred for suspicion of or had a final diagnosis of third nerve palsy. Demographics, referral encounter details, physical examination findings, final diagnoses, timing of arterial imaging, etiologies of third nerve palsy, and details of patient harm were collected. RESULTS Of the 110 included patients, 62 (56.4%) were women, 88 (80%) were white, and the mean age was 61.8 ± 14.6 years. Forty (36.4%) patients received arterial imaging urgently. Patients suspected of third nerve palsy were not more likely to be sent for urgent evaluation (P = 0.29) or arterial imaging (P = 0.082) than patients in whom the referring doctor did not suspect palsy. Seventy-eight of 95 (82%) patients with a final diagnosis of third nerve palsy were correctly identified by referring providers. Of the 20 patients without any arterial imaging before neuro-ophthalmology consultation, there was a median delay of 24 days from symptom onset to imaging, and a median delay of 12.5 days between first medical contact for their symptoms and imaging. One patient was harmed as a result of delayed imaging. CONCLUSIONS Third nerve palsies were typically identified correctly, but referring providers failed to recognize the urgency of arterial imaging to rule out an aneurysmal etiology. Raising awareness of the urgency of arterial imaging may improve patient safety.

COVID-19 has led to a great deal of general suffering and an increased prevalence of psychiatric illness worldwide. Within the area of psychosis-risk syndromes, a highly heterogeneous clinical population, the picture is quite nuanced as the social restrictions resulting from the pandemic have reduced stress for some and increased it for others. Further, a number of pandemic-related societal and cultural changes have obfuscated the diagnostic and treatment landscape in this area as well. In this opinion article, we describe several prototypical cases, representative of presentations seen in our clinical high-risk (CHR) research programs. The cases highlight considerable clinical variability and, in addition, speak to the current complexities faced by diagnosticians and treatment providers. In addition to discussing these issues, this piece introduces potential solutions highlighting the promise of incorporating data-driven strategies to identify more homogenous CHR subtypes and employ precision medicine.

OBJECTIVE Advances in diabetes technology have transformed the treatment paradigm for type 1 diabetes, yet the burden of disease is significant. We report on a pivotal safety study of the first tubeless, on-body automated insulin delivery system with customizable glycemic targets. RESEARCH DESIGN AND METHODS This single-arm, multicenter, prospective study enrolled 112 children (age 6–13.9 years) and 129 adults (age 14–70 years). A 2-week standard therapy phase (usual insulin regimen) was followed by 3 months of automated insulin delivery. Primary safety outcomes were incidence of severe hypoglycemia and diabetic ketoacidosis. Primary effectiveness outcomes were change in HbA1c and percent time in sensor glucose range 70–180 mg/dL (“time in range”). RESULTS A total of 235 participants (98% of enrolled, including 111 children and 124 adults) completed the study. HbA1c was significantly reduced in children by 0.71% (7.8 mmol/mol) (mean ± SD: 7.67 ± 0.95% to 6.99 ± 0.63% [60 ± 10.4 mmol/mol to 53 ± 6.9 mmol/mol], P < 0.0001) and in adults by 0.38% (4.2 mmol/mol) (7.16 ± 0.86% to 6.78 ± 0.68% [55 ± 9.4 mmol/mol to 51 ± 7.4 mmol/mol], P < 0.0001). Time in range was improved from standard therapy by 15.6 ± 11.5% or 3.7 h/day in children and 9.3 ± 11.8% or 2.2 h/day in adults (both P < 0.0001). This was accomplished with a reduction in time in hypoglycemia CONCLUSIONS This tubeless automated insulin delivery system was safe and allowed participants to significantly improve HbA1c levels and time in target glucose range with a very low occurrence of hypoglycemia.

Background : Previous research has investigated the percentage of maximal outcome improvement (MOI) for the American Shoulder and Elbow Surgeons (ASES) and Simple Shoulder Test (SST) scores after reverse total shoulder arthroplasty (rTSA); however, few other outcome scores have been validated. The purpose of this study was to establish thresholds of MOI percentage for the Single Assessment Numeric Evaluation (SANE) and subjective Constant-Murley (Constant) scores associated with patient satisfaction at two-years following rTSA. Methods : A retrospective review of institutional registry data for all patients who underwent primary rTSA between 09/2016 and 02/2018 was performed. All patients completed the ASES, SANE, and Constant outcome measures preoperatively and at a minimum of two-years postoperatively. Changes were assessed with Wilcoxon signed-rank tests. MOI percentage was defined as the score improvement from baseline divided by the highest possible improvement from baseline based on the maximum value of the outcome score used. Receiver operating characteristic (ROC) analyses were used to determine optimal MOI percentage thresholds associated with postoperative satisfaction. Stepwise multivariate logistic regression was performed to identify variables associated with achieving the MOI. Results : A total of 105 patients were included in the final analysis, with a mean (±standard deviation) age of 70.0±7.5 years and BMI of 28.9±5.6 kg/m2. The majority of patients were satisfied postoperatively (81.0%). Statistically significant increases were observed from baseline to two-years postoperatively for the outcome measures assessed (P Conclusion : Achieving 66.9%, 71.0%, and 37.5% of the MOI for the ASES, SANE, and Constant scores is associated with postoperative satisfaction following rTSA. Comorbid diabetes and diagnosis of rotator cuff arthropathy were significantly associated with a decreased likelihood of MOI achievement. Level of Evidence : Level III; Retrospective Case Series (Prognostic)

Background and Aims: Expert endoscopists previously reported ERCP outcomes for the first commercialized single-use duodenoscope. We aimed to document usability of this device by endoscopists with different levels of ERCP experience. Methods: Fourteen “expert” (>2000 lifetime ERCPs) and 5 “less-expert” endoscopists performed consecutive ERCPs in patients without altered pancreaticobiliary anatomy. Outcomes included ERCP completion for the intended indication, rate of crossover to another endoscope, device performance ratings, and serious adverse events. Results: Two hundred ERCPs including 81 (40.5%) with high complexity (American Society for Gastrointestinal Endoscopy grades 3-4) were performed. Crossover rate (11.3% vs 2.5%, P =.131), ERCP completion rate (regardless of crossovers) (96.3% vs 97.5%, P =.999), median ERCP completion time (25.0 vs 28.5 minutes, P =.130), mean cannulation attempts (2.8 vs 2.8, P =.954), and median overall satisfaction with the single-use duodenoscope (8.0 vs 8.0 [range, 1.0-10.0], P =.840) were similar for expert versus less-expert endoscopists, respectively. The same metrics were similar by procedural complexity except for shorter median completion time for grades 1 to 2 versus grades 3 to 4 (P Conclusions: In consecutive ERCPs including high complexity procedures, endoscopists with varying ERCP experience had good procedural success and reported high device performance ratings. (Clinical trial registration number: NCT04223830.)

OBJECTIVE The facial recess approach during translabyrinthine surgery has been used to expose the eustachian tube (ET) for packing. We sought to determine the effect of this technique on the development of postoperative nasopharyngeal cerebrospinal fluid (CSF) leaks. PATIENTS Cohorts of patients with cerebellopontine angle schwannomas who underwent a facial recess approach or no facial recess approach were matched based on tumor size. INTERVENTIONS Translabyrinthine surgery for tumor resection. MAIN OUTCOME MEASURES Postoperative CSF leaks were recorded and nasopharyngeal CSF leaks were utilized as the primary outcome measure. RESULTS Using an exact matching protocol based on tumor size, 102 patients were included in each group (204 total, 111 female, 93 male). Overall, 9 patients (4.4%) demonstrated a postoperative nasopharyngeal CSF leak. Postoperative CSF rhinorrhea was noted in 3.9% of the group who underwent a facial recess approach for packing of the ET and 4.9% of the group who did not undergo a facial recess approach. This rate was not significantly different between groups (p = 0.99, Odds ratio: 0.79, 95% CI: 0.15-3.8). Secondary variables including age, tumor size, a diagnosis of NF2, and the packing material used were not significant predictors of nasopharyngeal CSF leaks. CONCLUSIONS CSF rhinorrhea is infrequent after translabyrinthine surgery. The incidence of this complication is not affected by whether or not a facial recess approach is performed during surgery to pack the ET. Based on these data, use of this technique should be based on surgeon comfort and preference.

Pelvic fractures and sacroiliac joint (SI) diastasis are debilitating injuries which can drastically decrease an individual's functional capacity, and lead to significant morbidity and mortality. In younger, healthier populations, pelvic fractures are usually the result of sudden traumatic forces, such as a motor vehicle collision. Atraumatic pelvic fractures can also occur, and are most commonly due to age related changes and osteoporosis. Even with prompt surgical management, pelvic fractures often result in a host of challenging complications such as disruption of the SI joint with subsequent limitations in mobility and chronic pain. In this case report, we present a novel treatment of SI diastasis, secondary to corticosteroid induced osteoporosis and pelvic fractures. We performed percutaneous bilateral poly-methyl-methacrylate (PMMA) SI joint fusions under CT-guidance. Here we describe a case of bilateral SI joint CT guided percutaneous arthroplasty for osteoporotic SI joint diastasis and pelvic fractures, resulting in a rapid resolution of SI joint pain and restoration of the ability to ambulate in a previously wheelchair-bound patient. This may be of particular benefit in patients who are poor surgical candidates who experience osteoporotic fractures and would be otherwise unable to receive definitive operative management of their pathologic fractures.

Background Shocks near defibrillation threshold (nDFT) strength commonly extinguish all ventricular fibrillation (VF) wavefronts, but a train of rapid, well-organized postshock activations (PAs) typically appears before sinus rhythm ensues. If one of the PA waves undergoes partial propagation block (wavebreak), reentry may be induced, causing VF to reinitiate and the shock to fail. Objective The purpose of this study was to determine whether wavebreak leading to VF reinititation following nDFT shocks occurs preferentially at the right ventricular insertion (RVI), which previous studies have identified as a key site for wavebreak. Methods We used panoramic optical mapping to image the ventricular epicardium of 6 isolated swine hearts during nDFT defibrillation episodes. After each experiment, the hearts were fixed and their geometry scanned with magnetic resonance imaging (MRI). The MRI and mapping datasets were spatially coregistered. For failed shocks, we identified the site of the first wavebreak of a PA wave during VF reinitiation. Results We recorded 59 nDFT failures. In 31 of these, the first wavebreak event occurred within 1 cm of the RVI centerline, most commonly on the anterior side of the right ventricular insertion (aRVI) (23/31). The aRVI region occupies 16.8% ± 2.5% of the epicardial surface and would be expected to account for only 10 wavebreaks if they were uniformly distributed. By χ2 analysis, aRVI wavebreaks were significantly overrepresented. Conclusion The anterior RVI is a key site in promoting nDFT failure. Targeting this site to prevent wavebreak could convert defibrillation failure to success and improve defibrillation efficacy.

Background: The objective of this study was to assess the safety and effectiveness of the first commercial configuration of a tubeless automated insulin delivery system, Omnipod® 5, in children (6–13.9 years) and adults (14–70 years) with type 1 diabetes (T1D) in an outpatient setting. Materials and Methods: This was a single-arm, multicenter, prospective clinical study. Data were collected over a 14-day standard therapy (ST) phase followed by a 14-day hybrid closed-loop (HCL) phase, where participants (n = 36) spent 72 h at each of three prespecified glucose targets (130, 140, and 150 mg/dL, 9 days total) then 5 days with free choice of glucose targets (110–150 mg/dL) using the Omnipod 5. Remote safety monitoring alerts were enabled during the HCL phase. Primary endpoints were difference in time in range (TIR) (70–180 mg/dL) between ST and HCL phases and proportion of participants reporting serious device-related adverse events. Results: Mean TIR was significantly higher among children in the free-choice period overall (64.9% ± 12.2%, P

This article presents a comprehensive review of the use of quantitative measurements based on breast images to assess fat retention, breast aesthetics, and fat necrosis after autologous fat grafting. Breast volume measured from MRI and 3-dimensional surface images is widely used as a measure of fat retention. Breast aesthetics are assessed from a combination of anthropometric (distance and contour) measurements on breast surface images. Examination of radiologic images (ultrasonography, mammography, and MRI) is utilized to assess fat necrosis. The article discusses implementation guidelines for objective outcome assessment to support robust quantification and enable investigations of fat grafting efficacy. Level of Evidence: 4

Background: Extracorporeal cardiopulmonary resuscitation (ECPR) for refractory cardiac arrest has improved mortality in post-cardiac surgery patients; however, loss of neurologic function remains one of the main and devastating complications. We reviewed our experience with ECPR and investigated the effect of cannulation strategy on neurologic outcome in adult patients who experienced cardiac arrest following cardiac surgery that was managed with ECPR. Methods: Patients were categorized by central versus percutaneous peripheral VA-extracorporeal membrane oxygenation (ECMO) cannulation strategy. We reviewed patient records and evaluated in-hospital mortality, cause of death, and neurologic status 72 hours after cannulation. Results: From January 2010 to September 2019, 44 patients underwent post-cardiac surgery ECPR for cardiac arrest. Twenty-six patients received central cannulation; 18 patients received peripheral cannulation. Mean post-operative day of the cardiac arrest was 3 and 9 days (p = 0.006), and mean time between initiation of CPR and ECMO was 40 ± 24 and 28 ± 22 minutes for central and peripheral cannulation, respectively. After 72 hours of VA-ECMO support, 30% of centrally cannulated patients versus 72% of peripherally cannulated patients attained cerebral performance status 1–2 (p = 0.01). Anoxic brain injury was the cause of death in 26.9% of centrally cannulated and 11.1% of peripherally cannulated patients. Survival to discharge was 31% and 39% for central and peripheral cannulation, respectively. Conclusions: Peripheral VA-ECMO allows for continuous CPR and systemic perfusion while obtaining vascular access. Compared to central cannulation, a peripheral cannulation strategy is associated with improved neurologic outcomes and decreased likelihood of anoxic brain death.

Background The patient acceptable symptomatic state (PASS) represents clinical improvement following surgery that patients deem as satisfactory; however, thresholds for achieving this clinical benchmark have not yet been established beyond 1 year following primary and reverse shoulder arthroplasty. Methods A prospectively maintained registry was retrospectively queried for patients undergoing either a primary TSA or RTSA at a single institution between November, 2015 and October, 2017. All patients completed the ASES, SANE, and Constant patient-reported outcome (PRO) scores at the 2-year time point. PASS threshold scores were calculated using anchor-based methodology with subsequent calculation of achievement rates. Multivariate logistic regression was used to identify demographic and clinical variables associated with the likelihood of PASS achievement. Results A total of 93 TSA (mean age 61.4 ± 8.5 years, 32.3% female) and 111 RTSA (mean age 70.0 ± 8.1 years, 51.4% female) patients met final inclusion criteria. One-hundred sixty-five patients (80.8%) responded to the binary anchor question as “satisfied” regarding their surgical outcome. The PASS cutoffs for ASES, SANE, and Constant were 81.7, 85.7, and 24.0, respectively (AUC > 80%), with PASS achievement rates ranging from 50.7% to 59.9% for the entire study population and 66.7% to 83.3% for a risk-stratified subgroup. Patients undergoing TSA had a significantly higher PASS achievement rate relative to RTSA (P = .010) for ASES. Independent risk factors for decreased PASS achievement included lower preoperative PRO score, prior shoulder surgery, sedentary lifestyle, smoking, workers’ compensation status, and diabetes mellitus (DM). Conclusion The majority of patients reach the PASS benchmark by 2 years after shoulder arthroplasty, with an optimal subgroup of risk-stratified patients achieving PASS at a rate greater than 80% for ASES. Patients undergoing TSA have a higher likelihood of reaching the PASS than patients undergoing RTSA, independent of other variables. Lower baseline outcome scores, prior shoulder surgery, smoking, and sedentary lifestyle are associated with lower PASS rates after TSA. Worker's compensation status and comorbid DM are predictive of reduced PASS rates after RTSA. Primary diagnosis and glenoid morphology did not have a significant impact on the rate of achieving the PASS. This information is valuable for patient selection and counseling prior to shoulder arthroplasty. Level of Evidence Level III; Prognostic Study; Retrospective Case Series.

Hypothesis The purpose of this study was to perform a systematic review to identify cost-analysis studies pertaining to shoulder arthroplasty, provide a comprehensive review of published studies, and critically evaluate the quality of the available literature using the Quality of Health Economic Studies (QHES) instrument. Methods A systematic review of the literature was performed to identify cost analyses examining shoulder arthroplasty. The inclusion criteria included studies pertaining to either shoulder hemiarthroplasty (HA), total shoulder arthroplasty (TSA), or reverse TSA. Articles were excluded based on the following: nonoperative studies, nonclinical studies, studies not based in the United States, and studies in which no cost analysis was performed. The quality of studies was assessed using the QHES instrument. One-sided Fisher exact testing was performed to identify predictors of both low-quality (ie, QHES score 75th percentile) cost analyses based on items within the QHES checklist. Results Of the 196 studies screened, 9 were included. Seven studies conducted cost analyses comparing reverse TSA vs. arthroscopic rotator cuff repair, HA, or total hip arthroplasty, and 2 studies examined TSA vs. HA for primary glenohumeral arthritis. The average QHES score among all studies was 86.22 ± 13.39 points. Failure to include an annual cost discounting rate was associated with a low-quality QHES score (P = .03). In addition, including a discussion of the magnitude and direction of potential biases was associated with a high-quality score (P = .03). Conclusions Shoulder arthroplasty is a cost-effective procedure when used to treat a multitude of shoulder pathologies. The overall quality of cost analysis in shoulder arthroplasty is relatively good, with an average QHES score of 86.22 points. Studies failing to include an annual cost discounting rate are more likely to score below the 25th percentile, whereas those including a discussion of the magnitude and direction of potential biases are more likely to achieve a score in excess of the 75th percentile.

Background Negative symptoms are a core aspect of psychopathology in schizophrenia. Currently available pharmacological agents have proven minimally efficacious for remediating negative symptoms. A promising treatment avenue is the intranasal administration of the neuropeptide oxytocin. However, there have been inconsistencies in effects of oxytocin on negative symptoms throughout the literature, and factors leading to inconsistent effects are unclear. Methods We conducted a systematic review and meta-analysis of randomized clinical trials to compare the effectiveness of oxytocin with placebo for the treatment of negative symptoms and determine moderators of treatment effect. Random effects meta-analyses and dose-response meta-analysis were performed on mean changes in negative symptoms. Results In an initial analysis of all 9 identified randomized clinical trials, intranasal oxytocin showed no significant effect on negative symptoms. For higher doses (>40–80 IU), a beneficial effect on negative symptoms was found with a moderate effect size, but this effect disappeared after exclusion of 1 outlier study. The dose-response meta-analysis predicted that higher doses of oxytocin may be more efficacious for negative symptoms. For positive symptoms, no beneficial effect of oxytocin was found in the main meta-analysis, but the dose-response meta-analysis suggested a potential advantage of higher doses. Conclusions The present results show no consistent beneficial effect of intranasal oxytocin for the treatment of negative and positive symptoms. The dose-response meta-analysis does not allow drawing any firm conclusions but suggests that high doses of intranasal oxytocin may be more efficacious. If future studies are conducted, an effort to reach adequate CNS concentrations for a sufficient duration is required.

Objective To describe a conservative approach to care of an adult patient presenting with chronic abdominal wall pain persisting two years following abdominal surgery. Clinical features A 62-year-old female presented to a chiropractic neurologist with abdominal wall pain and sensation deficits. Her prior surgical history and a positive Carnett's sign indicated anterior cutaneous nerve entrapment syndrome (ACNES). Intervention and outcome Treatments, including manual therapy, rehabilitation, and desensitization techniques, significantly reduced the frequency and severity of the ACNES symptoms. Conclusion ACNES can be effectively managed via nonsurgical and non-pharmacological treatment methods.

Background: Data are limited on the need for and benefits of pump setting optimization with automated insulin delivery. We examined clinical management of a closed-loop control (CLC) system and its relationship to glycemic outcomes. Materials and Methods: We analyzed personal parameter adjustments in 168 participants in a 6-month multicenter trial of CLC with Control-IQ versus sensor-augmented pump (SAP) therapy. Preset parameters (BR = basal rates, CF = correction factors, CR = carbohydrate ratios) were optimized at randomization, 2 and 13 weeks, for safety issues, participant concerns, or initiation by participants' usual diabetes care team. Time in range (TIR 70–180 mg/dL) was compared in the week before and after parameter changes. Results: In 607 encounters for parameter changes, there were fewer adjustments for CLC than SAP (3.4 vs. 4.1/participant). Adjustments involved BR (CLC 69%, SAP 80%), CR (CLC 68%, SAP 50%), CF (CLC 44%, SAP 41%), and overnight parameters (CLC 62%, SAP 75%). TIR before and after adjustments was 71.2% and 71.3% for CLC and 61.0% and 62.9% for SAP. The highest baseline HbA(1c) CLC subgroup had the largest TIR improvement (51.2% vs. 57.7%). When a CR was made more aggressive in the CLC group, postprandial time >180 mg/dL was 43.1% before the change and 36.0% after the change. The median postprandial time

Background Management of patients with interstitial lung disease (ILD) requires subspecialized, comprehensive, multidisciplinary care. The Pulmonary Fibrosis Foundation established the Care Center Network (CCN) in 2013 with identified criteria to become a designated CCN site. Despite these criteria, the essential components of an ILD clinic remain unknown. Research Questions How are ILD clinics within the CCN structured? What are the essential components of an ILD clinic according to ILD physician experts, patients, and caregivers? Study Design and Methods This study had three components. First, all 68 CCN sites were surveyed to determine the characteristics of their current ILD clinics. Second, an online, three-round modified Delphi survey was conducted between October and December 2019 with 48 ILD experts participating in total. Items for round 1 were generated using expert interviews. During rounds 1 and 2, experts rated the importance of each item on a 5-point Likert scale. The a priori threshold for consensus was more than 75% of experts rating an item as important or very important. In round 3, experts graded items that met consensus and ranked items deemed essential for an ILD clinic. Third, ILD patient and caregiver focus groups were conducted and analyzed for content to determine their perspectives of an ideal ILD clinic. Results Forty items across four categories (members, infrastructure, resources, and multidisciplinary conference) achieved consensus as essential to an ILD clinic. Patient and caregiver focus groups identified three major themes: comprehensive, patient-centered medical care; expanded access to care; and comprehensive support for living and coping with ILD. Interpretation The essential components of an ILD clinic are well-aligned between physician experts and patients. Future research can use these findings to evaluate the impact of these components on patient outcomes and to inform best practices for ILD clinics throughout the world.

Aims The aim of this study is to characterize healthcare resource utilization and costs in patients with heart failure with reduced ejection fraction (HFrEF) following a worsening heart failure event. Methods and results This was a retrospective observational cohort analysis. Patients with HFrEF were identified from the PINNACLE Registry and linked to a nationwide pharmacy and medical claims database. Worsening heart failure was defined as stable heart failure with a subsequent hospitalization and/or intravenous diuretic therapy. Healthcare resource use and costs in 2015 US dollars were analysed for dispensed prescriptions, outpatient encounters, and hospital encounters. Among 11 064 patients with HFrEF, 3087 (27.9%) experienced a worsening heart failure event during an average follow‐up of 973 days. During the first 30 days after the worsening event, 19.8% of patients had hospital readmissions with heart failure as the primary or secondary diagnosis. During that same time period, mean per patient heart failure‐related healthcare resource use included 1.3 prescriptions, 0.5 practitioner visits, and 0.5 hospital encounters (admissions, observations, or emergency care), for an average total medical cost of $8779 per patient including $5359 in heart failure‐related costs. During the first year following worsening heart failure onset, mean per patient total and heart failure‐related costs were $62 615 and $35 329, respectively. Conclusions The economic burden following a worsening heart failure event calls for further review of methods to prevent progressive disease, improve adherence to guideline‐directed therapy, and develop novel treatments and care strategies to moderate further progression.

The clinical research we do to improve our understanding of disease and to develop new therapies has temporarily been delayed as the global health-care enterprise has focused its attention on those impacted by coronavirus disease 2019 (COVID-19). Although rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are decreasing in many areas, many locations continue to have a high prevalence of infection. Nonetheless, research must continue and institutions are considering approaches to restarting non-COVID-related clinical investigation. Those restarting respiratory research must navigate the added planning challenges that take into account outcome measures that require aerosol-generating procedures. Such procedures potentially increase risk of transmission of SARS-CoV-2 to research staff, use limited personal protective equipment, and require conduct in negative-pressure rooms. One must also be prepared to address the potential for COVID-19 resurgence. With research subject and staff safety and maintenance of clinical trial data integrity as the guiding principles, here we review key considerations and suggest a step-wise approach for resuming respiratory clinical research.

Aortic injury is a frequently encountered condition that can present as a life-threatening emergency. When this injury occurs in the retroperitoneal portion of the aorta, it can be difficult to diagnose and treat because of the location. Although surgical repair remains the mainstay of treatment, surgery might not be an option for some patients. We have presented a case of a 54-year-old nonoperative candidate who had experienced iatrogenic retroperitoneal abdominal aortic rupture with pseudoaneurysm formation. The patient was successfully treated with the novel use of a proven technique: direct percutaneous embolization of the pseudoaneurysm sac via a translumbar approach under image guidance.

INTRODUCTION Breast reconstruction surgery is an integral part of breast cancer treatment that aims to restore breast appearance after mastectomy. We assessed breast symmetry following breast reconstruction using measures of distance and volume. MATERIAL AND METHODS Patients undergoing breast reconstruction surgery were enrolled in an IRB approved study from 2011 to 2014 at The University of Texas MD Anderson Cancer Center. We utilized pre- and post-operative 3D surface images (3dMDtorso, 3dMD LLC, Atlanta, GA) from 53 women who had completed the breast reconstruction process (83% at 18 months (M), 9.4% at 12M and 7.6% at 9M). Patients provided approved consent. Thirty-six women had bilateral and 17 had unilateral surgery. Eleven patients in the unilateral group had symmetry surgery on the contralateral breast (5 had mastopexy, 4 had reduction, 1 had augmentation, and 1 had augmentation and mastopexy). Within the bilateral group, 9 patients underwent autologous reconstruction, 21 received implants, and 6 had mixed (autologous and implant) procedures. Within the unilateral group, there were 10 implant and 7 autologous reconstructions. We measured the sternal notch (SN) to lowest visible point (LVP) distance and volume for each breast. Breast symmetry was assessed using 1) Difference between the left and right breasts for the SN-LVP distance and volume measures, 2) SN-LVP distance ratio and volume ratio computed using values for the left and right breast. The smaller value was divided by the larger, so that a ratio of 1.0 indicated perfect symmetry [1]. Differences < 5 mm for SN-LVP distance and < 50 cc for breast volume were used as indicators of symmetry [1]. RESULTS Overall, pre-operatively 50.9% patients showed a SN-LVP difference < 5 mm compared to 35.9% post-operatively, whereas 43.4% showed a breast volume difference < 50 cc pre-operatively compared to 62.3% post-operatively. Mean pre- and post-operative SN-LVP distance ratios were found to be 0.97 ± 0.03 and 0.96 ± 0.03, respectively, whereas the breast volume ratios were 0.91 ± 0.06 and 0.92 ± 0.08, respectively. Shapiro-Wilk tests showed non-normal distribution for both ratios; thus, non-parametric analysis was performed using Mann-Whitney U-test and, for matched pairs, the Wilcoxon Matched Pairs Sign-Ranked test. For both distance and volume ratios, we failed to reject the null hypothesis that the median of the paired differences between the pre- and post-operative values was zero. Also, no significant differences were found for both ratios when comparing autologous and implant-based surgeries. Bilateral reconstructions were compared to unilateral procedures that included a contralateral symmetry procedure. Significantly higher distance ratios (0.97 ± 0.03, median of 0.98, p = 0.005) were found for bilateral reconstructions compared to unilateral (0.94 ± 0.04, median of 0.94), but no differences in volume ratios were noted. Significant differences were noted for both distance (p = 0.033) and volume (p = 0.009) ratios when comparing bilateral (distance: 0.96 ± 0.02, median of 0.97 and volume: 0.96 ± 0.03, median of 0.97) to unilateral implant-based reconstructions (distance: 0.93 ± 0.04, median of 0.94 and volume: 0.91 ± 0.05, median of 0.90), but no difference in symmetry was found between unilateral and bilateral autologous reconstructions. CONCLUSION Distance symmetry was noted in a higher percentage of the pre-operative population compared to post-operative, whereas a larger proportion of the post-operative patients showed volume symmetry compared to the pre-operative group. Implant-based bilateral procedures showed improved symmetry compared to the unilateral procedures. REFERENCES 1.Cheong AL, Liu J, Reece GP, Nicklaus KM, Bordes MC, Hanson SE, Markey MK, Merchant, FA “Natural Breast Symmetry in Preoperative Breast Cancer Patients”, Plastic and Reconstructive Surgery - Global Open: 2019;7(7):e2297. Citation Format: Thao Bui, Urmila Sampathkumar, Zhale Nowroozilarki, Jun Liu, Mary Catherine Borders, Summer E Hanson, Gregory P Reece, Mia K Markey, Fatima A Merchant. Symmetry of breasts following reconstructive surgery [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-24.

Daina B Esposito,1 Vibha CA Desai,1 Judith J Stephenson,1 M Soledad Cepeda,2 Jennifer G Lyons,1 Crystal N Holick,1 Gregory P Wedin,3 Stephan Lanes1 On behalf of members of the REMS Program Companies Metrics Subteam1HealthCore, Inc., Wilmington, DE, USA; 2Janssen Research and Development, Titusville, NJ, USA; 3Upsher-Smith Laboratories, LLC, Maple Grove, MN, USACorrespondence: Judith J StephensonHealthCore Inc, 123 Justison Street, Suite 200, Wilmington, DE, 19801, USATel +1 302-547-5770Email jstephenson@healthcore.comBackground/Rationale: The US Food and Drug Administration (FDA) approved a Risk Evaluation and Mitigation Strategy (REMS) for extended release/long-acting (ER/LA) opioids in 2012. The purpose of this study was to assess patient knowledge of the safe use of these products following implementation of the REMS and to determine possible effects of the REMS, including impact on medication access.Objective: To assess patient knowledge of safe use of ER/LA opioids and use of REMS patient education tools such as the Medication Guide (MG) and Patient Counseling Document (PCD).Methods: This was a cross-sectional survey of commercially insured (Commercial) and Medicare Advantage-insured (Medicare) adults with ≥ 1 pharmacy claim for an ER/LA opioid (10/01/2015 – 02/28/2017) in the HealthCore Integrated Research Database and Medicaid-insured (Medicaid) adult members of a research panel, about their knowledge of safe use of ER/LA opioids and receipt/comprehension of the MG and PCD.Results: Survey respondents consisted of 382 Commercial, 43 Medicare and 40 Medicaid adults. While ≥ 95% of respondents received and read the MG, fewer were aware of the PCD (Commercial: 47%, Medicare: 65%, Medicaid: 53%). Almost 75% of the knowledge questions were answered correctly by ≥ 80% of all respondents; fewer respondents recognized that use of opioids as directed can lead to death (Commercial: 73%, Medicare: 56%, Medicaid: 63%), the MG should be read at each dispensing (Commercial: 78%, Medicare: 53%, Medicaid: 75%), opioids should not be stored in the medicine cabinet (Commercial: 77%, Medicare: 79%, Medicaid: 58%), missed doses should not be taken as soon as possible (Commercial: 56%, Medicare: 51%, Medicaid: 50%), and pills should not be crushed (Commercial: 85%, Medicare: 67%, Medicaid: 52%).Conclusion: Although most respondents reported reading and understanding the MG and exhibited knowledge of safe use of ER/LA opioids, providers’ use of the PCD and increased understanding of safe use core messages need reinforcement.Keywords: Risk Evaluation and Mitigation Strategy, opioids, patient knowledge

The aldosterone‐to‐renin ratio (ARR) is a common screening test for primary aldosteronism in hypertensives. However, patients often use medications that could confound the ARR and, thereby, reduce the interpretability of the test. Since it is not always feasible to stop such medication, several drugs that are supposedly neutral with respect to the ARR have been recommended as alternative treatment. The objective of the present review is to explore whether sufficient evidence exists to justify the recommendations. To this end, we performed a systematic PubMed and Cochrane literature search regarding medications that may influence the ARR. Our review revealed that many commonly prescribed antihypertensives seem to have significant effects on renin, aldosterone, and resulting ARR values. However, the magnitude of these effects is poorly quantifiable with the present level of research. We conclude that several medications can affect the ARR. Not taking this into account could lead to misinterpretation of the ARR. Therefore, standardization of the medications used during ARR measurement is advisable for a reliable and accurate interpretation. Further research is needed to ascertain how to best optimize these medications.

Background Branch pulmonary artery (PA) stenosis (PAS) commonly occurs in patients with congenital heart disease (CHD). Prior studies have documented technical success and clinical outcomes of PA stent interventions for PAS but the impact of PA stent interventions on ventricular function is unknown. The objective of this study was to utilize 4D flow cardiovascular magnetic resonance (CMR) to better understand the impact of PAS and PA stenting on ventricular contraction and ventricular flow in a swine model of unilateral branch PA stenosis. Methods 18 swine (4 sham, 4 untreated left PAS, 10 PAS stent intervention) underwent right heart catheterization and CMR at 20 weeks age (55 kg). CMR included ventricular strain analysis and 4D flow CMR. Results 4D flow CMR measured inefficient right ventricular (RV) and left ventricular (LV) flow patterns in the PAS group (RV non-dimensional (n.d.) vorticity: sham 82 ± 47, PAS 120 ± 47; LV n.d. vorticity: sham 57 ± 5, PAS 78 ± 15 p p p Conclusion These results describe previously unknown consequences of PAS on ventricular function in an animal model of unilateral PA stenosis and show that PA stent interventions improve ventricular flow efficiency. This study also highlights the sensitivity of 4D flow CMR biomarkers to detect earlier ventricular dysfunction assisting in identification of patients who may benefit from PAS interventions.

Background The prevalence of burnout and depressive symptoms is high among physician trainees. Research Question What is the burden of burnout and depressive symptoms among fellows training in pulmonary and critical care medicine (PCCM) and what are associated individual fellow, program, and institutional characteristics? Study Design and Methods We conducted a cross-sectional electronic survey of fellows enrolled in pulmonary, PCCM, and critical care medicine training programs in the United States to assess burnout and depressive symptoms. Burnout symptoms were measured using the Maslach Burnout Index two-item measure. The two-item Primary Care Evaluation of Mental Disorders Procedure was used to screen for depressive symptoms. For each of the two outcomes (burnout and depressive symptoms), we constructed three multivariate logistic regression models to assess individual fellow characteristics, program structure, and institutional polices associated with either burnout or depressive symptoms. Results Five hundred two of the 976 fellows who received the survey completed it—including both outcome measures—giving a response rate of 51%. Fifty percent of fellows showed positive results for either burnout or depressive symptoms, with 41% showing positive results for depressive symptoms, 32% showing positive results for burnout, and 23% showing positive results for both. Reporting a coverage system in the case of personal illness or emergency (adjusted OR [aOR], 0.44; 95% CI, 0.26-0.73) and access to mental health services (aOR, 0.14; 95% CI, 0.04-0.47) were associated with lower odds of burnout. Financial concern was associated with higher odds of depressive symptoms (aOR, 1.13; 95% CI, 1.05-1.22). Working more than 70 hours in an average clinical week and the burdens of electronic health record (EHR) documentation were associated with a higher odds of both burnout and depressive symptoms. Interpretation Given the high prevalence of burnout and depressive symptoms among fellows training in PCCM, an urgent need exists to identify solutions that address this public health crisis. Strategies such as providing an easily accessible coverage system, access to mental health resources, reducing EHR burden, addressing work hours, and addressing financial concerns among trainees may help to reduce burnout or depressive symptoms and should be studied further by the graduate medical education community.

Background and importance Aneurysms of the posterior cerebral artery (PCA) are uncommon, estimated at less than 1% of all cerebral aneurysms, and less than half occur distal to the P1/2 junction. Unfortunately, the conventional bypass approach for PCA aneurysms-primarily occipital artery to distal PCA cortical branches-has a history of unsatisfying results. Clinical presentation A 42-yr-old female presented with Fisher 3 Hunt-Hess 2 subarachnoid hemorrhage secondary to ruptured distal PCA aneurysm. She was initially evaluated by the endovascular service, but due to recent subarachnoid hemorrhage, endovascular treatment with flow diversion and/or vessel sacrifice was felt to be relatively contraindicated and the patient was referred for surgical evaluation for possible bypass. The patient subsequently underwent surgery for trapping of aneurysm and concomitant superficial artery to distal PCA bypass. Conclusion A novel approach for the treatment of a ruptured distal PCA aneurysm is described, consisting of posterior transpetrosal exposure and division of the tentorium with superficial temporal artery to P3 bypass.

Objective To determine the utility of measuring free T4 index (FT4I) in patients with low free T4 (FT4) levels using immunoassay and normal thyroid-stimulating hormone for the evaluation of secondary hypothyroidism. Methods We performed a retrospective medical chart review of patients seen at a single institution as outpatients who had a simultaneously normal thyroid-stimulating hormone level, low FT4 level, and any FT4I measured between June 2014 and October 2016. Demographic, laboratory, and imaging data were collected. Using FT4I as the reference for diagnosis of hypothyroidism, the sensitivity and specificity of the FT4 immunoassay’s lower-limit thresholds were determined. Within each threshold group, available brain imaging and biochemical evaluation were categorized according to the presence or absence of pituitary disease. Results A total of 155 sets of result pairs (FT4 and FT4I) performed on 118 subjects were analyzed. The lower limit of a normal FT4 level by immunoassay at this institution was 0.93 ng/dL, though all pairs with FT4 ≥0.89 ng/dL had a normal FT4I. All pairs with FT4 ≤0.67 ng/dL had a low FT4I. No pituitary macroadenomas were identified in any subject, though the rates of pituitary imaging in this patient sample were low. Conclusion Patients with a borderline low FT4 level by immunoassay often have normal FT4I. In such patients at our center, significant structural and biochemical pituitary pathology was uncommon.