bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost-Effectiveness of Transtibial Bone-Anchored Prostheses Using Osseointegrated Fixation: From Challenges to Preliminary Data
Authors: Frossard Laurent , Ferrada Luciann , Quincey Tanya , Berg Debra
Published: May 2021

Introduction

This initial cost-effectiveness evaluation compared the provision of transtibial bone-anchored prostheses (TTA-BAPs) with socket-suspended prostheses (TTA-SSPs) over a 6-year time horizon from a governmental prosthetic care perspective. The purposes were to present ways we dealt with barriers encountered during the cost-effectiveness analysis. The objectives were to detail the extraction of baseline and incremental costs and utilities required to provide preliminary incremental cost-effectiveness ratios (ICERs) per quality-adjusted life-year (QALY).

Materials and Methods

This retrospective case-series study involved six participants fitted consecutively with TTA-SSP and TTA-BAP. Total costs combined actual and typical costs extracted from financial records and a schedule of allowable expenses, respectively. Baseline utilities were extracted from the literature, whereas incremental utilities were assumed.

Results

ICERs ranged between −$25,065 and $41,929 per QALY. Indicative ICER was approximately $11,400 per QALY. Provision of TTA-BAP was cost-effective and cost saving for 83% and 33% of cases, respectively.

Discussion

Educated choices were required to overcome unavailability of individual costs (e.g., creation of schedule of allowable expenses, blending of actual and typical costs) and utilities (e.g., extraction of baseline from literature, assumptions for incremental gain). Indicative ICER might lead to adoption of TTA-BAP, at least from an Australian governmental prosthetic care perspective.
Exclusive Endoscopic Laser-Stapedotomy: Feasibility of an Ovine Training Model
Authors: Beckmann Sven , Yacoub Abraam , Fernandez Ignacio Javier , Niederhauser Laura , Fermi Matteo , Caversaccio Marco , Bonali Marco , Anschuetz Lukas
Published: May 2021

Objective:

Stapedotomy is an effective treatment for conductive hearing loss associated with otosclerosis. However, the procedure, especially using the endoscopic technique requires extensive training and experience for optimal results. Due to limited training options in endoscopic stapes surgery, we aim to develop an ovine stapedotomy model and assess its feasibility for surgeons at different training levels.

Methods:

A fully endoscopic ovine laser-stapedotomy model was developed and described. During repetitive dissections, surgical time required for the different steps to assess the training curve and associated intraoperative complications were recorded in three surgeons of different training level. Additionally, subjective feedback was assessed.

Results:

Successful endoscopic laser-stapedotomy was performed in 25 cases in the ovine model. Assessment of surgical time revealed a stable curve for the experienced surgeon (mean 15:01 min) for the whole training with no intraoperative complications. The fellow showed a gradual reduction of surgical time from 27:21 (first five cases) to 24:10 minutes (last five cases) and the resident a reduction from 42:38 to 21:08 minutes respectively. The assessed learning curve for the trainees revealed a significant association between the operative time and observed intraoperative complications.

Discussion:

In this study, an ex-vivo model for exclusively endoscopic laser-stapedotomy was developed and tested for feasibility. We suggest the ovine model as a cost-effective, easily available, and realistic training model for future otologic surgeons. The surgeons were able to improve their performance with satisfactory results despite the small number of cases.
Trends in Health Care Utilization and Expenditures in the United States Across 5 Decades
Authors: Mortensen Karoline , Dean Emma Boswell , French Michael T. , Wang Nianyang , Chen Jie
Published: May 2021

Background:

Health care expenditures in the United States are high and rising, with significant increases over the decades. The delivery, organization, and financing of the health care system has evolved over time due to technological innovation, policy changes, patient preferences, altering payment mechanisms, shifting demographics, and other factors.

Objective:

The objective of this study was to examine trends over time in health care utilization and expenditures in the United States.

Research Design:

This analysis employs descriptive statistics to examine 5 decades of health care utilization and expenditure data from the Agency for Healthcare Research and Quality (AHRQ) for 1977–2017.

Measures:

Measures include utilization and expenditures (not charges) for inpatient, emergency department, outpatient physician, outpatient nonphysician, office-based physician, dental, and out-of-pocket retail prescription drugs.

Results:

We demonstrate that while health care expenditures have increased significantly overall and by type of care, utilization trends are less pronounced. The population of the United States grew 53% between 1977 and 2017, while annual total expenditures on health care increased by 208%. Amidst attention to out-of-pocket exposure for unexpected medical care bills, out-of-pocket payments for care have declined from 32% in 1977 to 12% in 2017 but increased in amount.

Conclusions:

This article provides the first extended snapshot of the dynamics of health care utilization and expenditures in the United States. Aspects of health care are much different today than in previous decades, yet the inpatient setting still dominates the expenditures.
Comparison of Nausea and Vomiting Associated With Amino Acid Formulations Coinfused With Peptide Receptor Radionuclide Therapy
Authors: Al-Toubah Taymeyah , Sikaria Dhiraj , Jesurajan Jose , Bottiglieri Salvatore , Smith Johnna , Pellé Eleonora , Hutchinson Tai , Strosberg Jonathan , El-Haddad Ghassan
Published: May 2021

Objectives

Positively charged amino acids (AA) such as arginine/lysine are coinfused with radiolabeled somatostatin analogs to reduce rates of nephrotoxicity. In the phase 3 NETTER-1 trial, commercial AA formulations were used in association with 177Lu–DOTA-0-Tyr3-Octreotate (DOTATATE). These formulations were also used in an early-access program (EAP) before regulatory approval of 177Lu-DOTATATE. Our program transitioned to compounded l-arginine 2.5%/l-lysine 2.5% in 0.9% NaCl after commercial approval of 177Lu-DOTATATE. We sought to compare rates of nausea/vomiting with arginine/lysine versus commercial parenteral AA formulations.

Methods

Rates of nausea/vomiting of all 20 EAP patients who received commercial AAs (15% Clinisol) were compared with the first 29 patients to receive 177Lu-DOTATATE after commercial approval and coinfused with arginine/lysine. Other parameters reviewed included infusion rates, need for PRN nausea medications, and other toxicities.

Results

Seventeen percent of patients who received compounded arginine/lysine experienced nausea, compared with 100% of patients in the EAP group (P < 0.0001). Infusion-related reactions occurred in 3% of the arginine/lysine cohort versus 35% in the EAP group. Infusion durations were substantially shorter in the arginine/lysine cohort (reduced by 61%).

Conclusions

Coinfusions of arginine/lysine with radiolabeled somatostatin analogs result in substantially lower rates of nausea/vomiting compared with commercial AA formulations designed for parenteral nutrition.
Quality Gaps in Management of Acute Pancreatitis
Authors: Mohy-ud-din Nabeeha , Deyl Ivana , Umar Shifa , Abdul-Baki Heitham , Morrissey Suzanne
Published: May 2021

Objectives

Acute pancreatitis (AP) is a leading cause of inpatient care among gastrointestinal conditions. Our study compares the management of AP and adherence to guidelines among teaching medicine, nonteaching medicine, and surgical services within the same center.

Methods

We performed a retrospective chart review of AP patients admitted to our center between January 2016 and January 2017 and analyzed the clinical and epidemiological data.

Results

Of 115 patients, 65% were admitted to medicine (IM), and 35% were admitted to surgery. Mean age was 53.9 (standard deviation [SD], 15) years, and 52% were males; 38.6% (n = 29) of IM patients were prescribed lactated Ringer's solution for fluid resuscitation (mean rate of 153 [SD, 44.98] mL/h on teaching and 113 [SD, 43.56] mL/h on the nonteaching service). Antibiotics were prescribed to 22.6% (n = 17) of IM patients. On the surgical service, 77.5% of patients were prescribed lactated Ringer's solution for fluid resuscitation (mean rate of 108.25 [SD, 1.19] mL/h); 52.5% of patients received antibiotics.

Conclusions

Adherence to guidelines for management of AP is inadequate, and nonuniformity exists across different services within the same institution. There is a need for quality improvement initiatives.
Cardiac Telemetry Downtime and Contingency Plan Development
Authors: Morrish Wendy , Soncrant Christina , Walsh-Irwin Colleen , Kulju Stephen , Gunnar William
Published: May 2021

Background:

Cardiac telemetry downtime may be planned or unplanned, causing a disruption in telemetry services with a potential to impact patient safety.

Problem:

Many cardiac telemetry units in the Veterans Health Administration (VHA) have contingency plans that do not adequately address telemetry downtime.

Approach:

This is a retrospective quality improvement analysis of VHA-reported cardiac telemetry downtime events from October 1, 2014, to Mar 31, 2020.

Outcomes:

Of 98 events, no patient harm was reported; 13% (n = 13) were planned downtime, 82% (n = 80) were unplanned downtime, 18% (n = 18) reported contingency plan use, 78% (n = 76) did not specify contingency plan use, and 32% (n = 31) reported events lasting 31 minutes to 6 hours in duration.

Conclusions:

The majority of reported cardiac telemetry downtime events were unplanned and without documented contingency plans. A robust contingency plan with defined staff roles and responsibilities will serve to lessen anxiety during downtimes and mitigate potential risk of patient harm.
Incidence and Clearance of Penile High-Risk Human Papillomavirus Infection and Their Determinants Among HIV-Negative Men Who Have Sex With Men
Authors: Nadar Hema J. , van Bilsen Ward P.H. , Marra Elske , Bruisten Sylvia , Heideman Daniëlle A.M. , Schim van der Loeff Maarten F.
Published: May 2021

Background

Men who have sex with men (MSM) are at increased risk of anogenital human papillomavirus (HPV) infections. We aimed to assess the incidence and clearance of penile high-risk HPV (hrHPV) infections and their determinants among HIV-negative MSM living in the Netherlands.

Methods

Between 2010 and 2015, HIV-negative MSM were semiannually tested for penile HPV and completed detailed questionnaires on health and sexual behavior. Self-collected penile swabs were tested for HPV DNA using SPF10-PCR DEIA/LiPA25 system. Type-specific hrHPV incidence (IR) and clearance rates (CR) were calculated for 12 hrHPV types (HPV-16, HPV-18, HPV-31, HPV-33, HPV-35, HPV-39, HPV-45, HPV-51, HPV-52, HPV-56, HPV-58, and HPV-59). Determinants of incidence and clearance of HPV-16 and HPV-18, separately, and combined 7 hrHPV types covered by the nonavalent vaccine were assessed by Poisson regression using generalized estimating equations for combined hrHPV types.

Results

We included 638 HIV-negative MSM, with a median age of 38 (interquartile range, 33–43) years. HPV-16 had an IR of 4.9/1000 person-months of observation at risk (PMO; 95% confidence interval [95% CI], 3.8–6.3) and CR of 90.6/1000 PMO (95% CI, 60.7–135.1). The IR and CR of HPV-18 were 3.4/1000 PMO (95% CI, 2.5–4.5) and 119.2/1000 PMO (95% CI, 76.9–184.8), respectively. Age and condom use during insertive anal sex were not associated with hrHPV incidence, whereas high number of recent sex partners was.

Conclusions

The relatively high IR and low CR of penile HPV-16 and HPV-18 among HIV-negative MSM correlates with their high prevalence and oncogenic potential. Incident HPV infections were associated with recent sexual risk behavior.
Endometrial Mesonephric-like Adenocarcinoma Presenting as an Ocular Lesion: A Case Report
Authors: Al Nabhani Safia , Doyle Aoife , Kennedy Susan , McVey Ruaidhri , Crown John , Gibbons David
Published: May 2021

Endometrial mesonephric-like carcinoma (ML-CA) is a recently recognized subtype of aggressive endometrial adenocarcinoma that is morphologically and immunophenotypically similar to mesonephric carcinoma but not typically associated with mesonephric remnants. Here, we report a case of 58-yr-old female who had a past medical history of fibroids and of irregular menstrual bleeding for ~20 yr who presented with visual disturbance. On further investigation, she was found to have a large choroidal peri-papillary tumor of the right eye. A presumptive diagnosis of choroidal melanoma was made. Right eye enucleation was performed, and microscopy revealed moderately differentiated metastatic adenocarcinoma. Further work up was advised. A uterine mass was identified on imaging followed by endometrial biopsy that showed a morphologically and immunohistochemically similar tumor to that in the eye. A hysterectomy was carried out and a malignant neoplasm with varying morphologic patterns including gland formation, solid sheets of tumor cells, cribriform, glomeruloid, spindled and papillary areas was seen. The immunohistochemical profile showed diffuse strong positivity for AE1/AE3, TTF1, P16, and vimentin. CD56, GATA3, Napsin A, and CD10 were focally positive. The neoplastic cells were negative for the following markers ER, PR, WT1, calretinin, and synaptophysin. PDL-1 was negative and mismatch repair protein was proficient. An identical KRAS mutation was detected in both the uterine corpus and ocular tumors. The findings are in keeping with a uterine mesonephric-like adenocarcinoma with an ocular metastasis. An Oncomine Focus—Mutation profile, Thermo-Fisher Scientific Inc., a 60 gene oncologic panel, performed on the ocular tumor, revealed no further mutations.
Leveraging Social and Structural Determinants of Health at the Centers for Disease Control and Prevention: A Systems-Level Opportunity to Improve Public Health
Authors: Lipshutz Judith A. , Hall Jeffrey E. , Penman-Aguilar Ana , Skillen Elizabeth , Naoom Sandra , Irune Ikovwa
Published: May 2021

Context:

Social and structural determinants of health (SDOH) have become part of the public health and health care landscape. The need to address SDOH is reinforced by morbidity and mortality trends, including a recent multiyear decrease in life expectancy and persistent health disparities. Leadership on SDOH-related efforts has come from public health, health care, private philanthropy, and nongovernmental entities.

Strategy:

The Centers for Disease Control and Prevention (CDC) has been addressing SDOH through both disease- or condition-specific programs and crosscutting offices. Guidance from public health partners in the field has led the CDC to consider more strategic approaches to incorporating SDOH into public health activities.

Implementation:

The CDC's crosscutting SDOH Workgroup responded to external recommendations to develop a specific vision and plan that aims to integrate SDOH into the agency's infrastructure. The group also sponsors CDC forums for sharing research and trainings on embedding SDOH in programs. The group created a Web site to centralize CDC SDOH research, data sources, practice tools, programs, and policies.

Progress:

The CDC has shown strong leadership in prioritizing SDOH in recent years. Individual programs and crosscutting offices have developed various models aimed at ensuring that public health research and practice address SDOH.

Discussion:

Building sustainable SDOH infrastructures in public health institutions that reach across multiple health topics and non–health organizations could increase chances of meeting public health morbidity and mortality reduction goals, including decreasing health disparities. Although public health priorities and socioeconomic trends will change over time, experience suggests that social and structural factors will continue to influence the public's health. The CDC and state, tribal, local, and territorial public health institutions have played important leadership roles in the system of community and service organizations that interface with communities they mutually serve to address SDOH. Continued capacity-building could help grow and sustain an SDOH infrastructure that advances this work.
Diagnosed Concussion and Undiagnosed Head Trauma Is Associated With Long-Term Concussion-Related Symptoms in Former College Football Players
Authors: Jacks Dean E. , Tereshko William D. , Moore Justin B.
Published: May 2021

Objective

Head trauma experienced in contact football is a growing health concern, but limited research has been conducted to assess associations between head trauma exposure and long-term concussion-related symptoms among former college football players.

Design

We surveyed 275 former college football players who were at least 10 yrs after competition to determine the association between head trauma exposure and concussion-related symptoms later in life. Respondents provided data on their youth, high school and college playing experience, undiagnosed head injury, diagnosed concussions, and eight concussion-related symptoms. A Poisson regression was conducted to examine the association between playing experience and reported head trauma with reported symptom count, and significance was set at P ≤ 0.05.

Results

Few participants reported diagnosed concussions in college (17.5%), but a large number reported undiagnosed football-related head injuries (68.8%) that might have resulted in a concussion. A few participants (40.7%) reported concussion-related symptoms. After controlling for age, high school football participation, and nonfootball concussions (lifetime), diagnosed concussions in high school or college did not significantly predict concussion symptoms later in life. However, undiagnosed football head injury (range = 1–8 injuries) reported 350%–855% greater concussion-related symptoms later in life.

Conclusions

Undiagnosed head injuries, which are less likely to be managed by a healthcare professional, were significantly associated with concussion-related symptoms later in life. These findings suggest that proper identification and management of concussions may prevent later symptoms, but more research is needed to test this conclusion.
Evolving Bilateral Hypermetabolic Axillary Lymphadenopathy on FDG PET/CT Following 2-Dose COVID-19 Vaccination
Authors: Weeks Joanna K. , O’Brien Sophia R. , Rosenspire Karen C. , Dubroff Jacob G. , Pantel Austin R.
Published: May 2021

A 50-year-old woman with stage IV sigmoid adenocarcinoma presented for restaging FDG PET/CT status post neoadjuvant chemotherapy/immunotherapy and diverting sigmoid colostomy. FDG PET/CT demonstrated FDG uptake in the known sigmoid mass and in abdominopelvic lymph node metastases. Bilateral, asymmetric, hypermetabolic axillary lymphadenopathy was also observed, an atypical pattern of spread for colon cancer. Further investigation revealed the patient had received both doses of COVID-19 vaccine in the 2 months prior to presentation. The authors discuss immunogenic nodal hypermetabolism following vaccination against COVID-19 and incorporating vaccination history to aid in PET/CT interpretation, especially in malignancies involving the axillae.
Late PET/CT Findings of COVID-19 Pneumonia With 2 Different Radiopharmaceuticals in a Patient
Authors: Şahin Özlem , Kaya Buğra , Aydın Zeynep , Karaağaç Mustafa , Kanyılmaz Gül
Published: May 2021

We present the 68Ga-PSMA and 18F-FDG PET/CT findings comparatively of a 67-year-old prostate cancer and malignant melanoma patient who had COVID-19 pneumonia 3 months ago. In 68Ga-PSMA PET/CT, ground-glass opacities showing markedly increased PSMA uptake were observed in the patient’s lungs. It was learned that the patient had COVID-19 pneumonia 3 months ago and was treated in the intensive care unit for 13 days. In 18F-FDG PET/CT, FDG uptake was minimal in the same areas. In the midterm period after COVID-19 pneumonia, lung PSMA uptake is more intense than FDG, which may help better understand the disease’s healing phase.
Orbital Lateral Cantal Distance Can Predict the Cephalometric Characteristic of Mandible in Iranian Population
Authors: Solhjoo Somayeh , Sayadi Mahtab , Navid Shadan , Toolee Heidar
Published: May 2021

Orbitofacial anthropometrics have become an important tool used in reconstructive surgery. The authors attempt to evaluate the relation between orbital lateral canthal distance and the cephalometric characteristic of mandible in Iranian population.

In a cross-sectional study, anthropometric parameters of face in 200 subjects (100 males and 100 females) with mean age of 34.39 ± 18.83 were evaluated by three-dimensional computed tomography imaging.

In this study, there was not a significant difference in the age of sex groups (P = 0.183). Also, there was no significant difference in the left and right mandible angle in different sex groups (P = 0.25, P 
= 
0.124, respectively). There were significant differences in the anterior mandible distance, inferior mandible angle distance (P = 0.0001) and lateral cantus distance of sex groups (P = 0.0001). There was a significant correlation between lateral contuse distance and left mandible angle (r = 0.226, P = 0.001), right mandible angle (r = 0.283, P = 0.00), mandible angle (r = -0.266, P = 0.00), anterior mandible angle distance (r = 0.655, P = 0.00), and inferior mandible angle distance (r = 0.582, P = 0.00).

Here, we conclude that orbital lateral canthal distance can predict the cephalometric characteristic of mandible in Iranian population.
Simultaneous Orthognathic Surgery With Asian Double Eyelid Suture Blepharoplasty
Authors: Khoo Lee Seng , Hsiao Yen-Chang , Huang Jung-Ju , Chang Frank Chun-Shin , Wang Yi-Chin , Liao Yu-Fang , Chen Zung-Chung , Lo Lun-Jou , Chen Jyh-Ping , Chen Yu-Ray
Published: May 2021

Background:

The main objective of contemporary orthognathic surgery is to correct dentofacial deformities. Nonetheless, many adjunct procedures to enhance the esthetic outcome in orthognathic surgical cases have been successfully incorporated to improve patient satisfaction. The authors report our preliminary experience of performing simultaneous orthognathic surgery with Asian double eyelid suture method blepharoplasty in the same surgical setting.

Method:

This case series report includes all 19 consecutive cases presenting to the Chang Gung Craniofacial Center for combined orthognathic surgery with Asian double eyelid suture method blepharoplasty. The double eyelid crease height was measured as the vertical line between the upper eyelid margin (eyelid lash) and the upper eyelid crease, observed at the mid-pupillary line with the eyes in primary gaze.

Results:

There were no complications or relapse reported within this time period. There was significant improvement in the left and right mid-pupillary double eyelid crease height postsurgery. There were no statistically significant differences between the left and right mid-pupillary double eyelid crease heights after surgery indicating good eyelid crease height symmetry bilaterally was obtained.

Conclusions:

Orthognathic surgery combined with suture method blepharoplasty can be safely performed in the same surgical setting without inappropriate rise in costs or operating room time. This case series demonstrates that excellent esthetic results can be obtained in simultaneous bimaxillary orthognathic surgery with suture method Asian blepharoplasty.
Simultaneous Use of Bioabsorbable and Nonbioabsorbable Packing Materials During Closed Reduction of a Nasal Bone Fractures
Authors: Han Song Hyun , Kim Soon Heum , Jo Dong In
Published: May 2021

The nasal packing material after closed reduction of nasal bone fracture may be bioabsorbable or nonbioabsorbable. To investigate the usefulness of the packing method using bioabsorbable and nonbioabsorbable materials simultaneously, a chart review was retrospectively performed involving 255 patients. Group A (n = 119), Nasopore (bioabsorbable) was cut appropriately and packed, and subsequently, supportive packing with Merocel (nonbioabsorbable) was performed. Group B (n = 78), nasal packing was performed with Vaseline roll gauze. Group C (n = 49), packed only Merocel. Pain and rhinorrhea were significantly lower in Merocel + Nasopore group (P < 0.05). It is thought that rhinorrhea is reduced by less mucosal irritation and maximizing the discharge absorption capacity by using Merocel and Nasopore simultaneously. By packing Nasopore first, pain is thought to be reduced by reducing the contact surface between Merocel and the injured mucosa and preventing a direct force to the fracture site. Therefore, our packing method, which uses Merocel and Nasopore simultaneously, can be recommended because it can provide sufficient support for the reduced fracture site, cause less pain, and maximize discharge absorption.
Surgical Management of Facial Fractures in Geriatric Patients
Authors: Yovev Tsanko , Burnic Aida , Kniha Kristian , Knobe Matthias , Hölzle Frank , Modabber Ali
Published: May 2021

Facial fractures comprise a substantial part of traumatology. Due to aging of the population, over the last 20 years, there has been a pattern of redistribution of these fractures with a higher incidence at an older age. The aim of this study was to retrospectively analyze the epidemiology, pattern, and surgical management of facial fractures in geriatric patients presenting at a single tertiary trauma center.

This study included patients aged ≥70 years who presented with facial bone fractures between 2008 and 2017 and were treated with surgical interventions. Parameters such as age, sex, American Society of Anesthesiologists classification, Glasgow Coma Scale score, fracture type, fracture mechanism, concomitant injuries, duration of hospitalization, and postoperative complications were evaluated.

A total of 300 patients were included: 118 men (39.3%) and 182 women (60.7%). The mean age was 78.8 years. An orbital floor fracture was the most common injury (35.1%). The most common cause of fracture was a fall at home (67%). A total of 113 patients (37.7%) had 162 concomitant injuries, 35 patients (11.7%) suffered from polytrauma, and 7 patients developed postoperative complications. The average length of stay was 1.67 days in the intensive care unit and 5.50 days in the standard ward. Polytrauma, pre-existing medical conditions, and oral anticoagulation had a significant impact on the duration of hospitalization.

Facial fractures are common in combination with other injuries. Women are more often affected than men, and falling at home is the most common cause of facial injuries. Postoperative complications are rare.
A Quantitative Analysis of Surgical Smoke Exposure as an Occupational Hazard
Authors: Stewart Camille L. , Raoof Mustafa , Lingeman Robert , Malkas Linda , Flores Viviana , Caldwell Kerry , Fong Yuman , Melstrom Kurt
Published: May 2021

Objective:

We hypothesized that OR airborne PM was different in quantity and mutagenic potential than office air and cigarette smoke.

Summary of Background Data:

Exposure to surgical smoke has been equated to cigarette smoking and thought to be hazardous to health care workers despite limited data.

Methods:

PM was measured during 15 operations in ORs with 24.8 ± 2.0 air changes/h, and in controls (cigarettes, office air with 1.9–2.9 air changes/h). Mutagenic potential was assessed by gamma Histone 2A family member X staining of DNA damage in small airway epithelial cells co-cultured with PM.

Results:

Average PM concentration during surgery was 0.002 ± 0.002 mg/m3 with maximum values at 1.08 ± 1.30 mg/m3. Greater PM correlated with more diathermy (ρ = 0.69, P = 0.006). Values were most often near zero, resulting in OR average values similar to office air (0.002 ± 0.001 mg/m3) (P = 0.32). Cigarette smoke average PM concentration was significantly higher, 4.8 ± 5.6 mg/m3 (P < 0.001). PM collected from 14 days of OR air caused DNA damage to 1.6% ± 2.7% of cultured cells, significantly less than that from office air (27.7% ± 11.7%, P = 0.02), and cigarette smoke (61.3% ± 14.3%, P < 0.001).

Conclusions:

The air we breathe during surgery has negligible quantities of PM and mutagenic potential, likely due to low frequency of diathermy use coupled with high airflow. This suggests that exposure to surgical smoke is associated with minimal occupational risk.
Synthetic blood and blood products for combat casualty care and beyond
Authors: Cap Andrew P. , Cannon Jeremy W. , Reade Michael C.
Published: May 2021

Synthetic biology adopts an engineering design approach to create innovative treatments that are reliable, scalable, and customizable to individual patients. Interest in substitutes for allogenic blood components, primarily red blood cells and platelets, increased in the 1980s because of concerns over infectious disease transmission. However, only now, with emerging synthetic approaches, are such substitutes showing genuine promise. Affordable alternatives to donated blood would be of enormous benefit worldwide. Several approaches to replacing the oxygen-carrying function of red cells are under advanced investigation. Hemoglobin-based oxygen carriers incorporate modifications to reduce the renal toxicity and nitric oxide scavenging of free hemoglobin. While use of earlier-generation hemoglobin-based oxygen carriers may be limited to circumstances in which blood transfusion is not an option, recent advances in chemical modification of hemoglobin may eventually overcome such problems. Another approach encases hemoglobin molecules in biocompatible synthetic nanoparticles. An alternative is the ex vivo production of red cells in bioreactors, with or without genetic manipulation, that offers the potential of a universal donor product. Various strategies to manufacture synthetic platelets are also underway, ranging from simple phospholipid liposomes encapsulating adenosine diphosphate and decorated with fibrinogen fragments, to more complex capsules with multiple receptor peptide sequences. Ex vivo production of platelets in bioreactors is also possible including, for example, platelets derived from induced pluripotent stem cells that are differentiated into a megakaryocytic lineage. Prior to clinical use, trials assessing synthetic blood components must evaluate meaningful safety and effectiveness outcomes in relatively large numbers of critically ill patients. Overcoming these challenges may be as much a hurdle as product design. This article reviews the state of the science of the synthetic biology approach to developing blood component substitutes.
Injury characteristics, initial clinical status, and severe injuries associated with spinal fractures in a retrospective cohort of 506 trauma patients
Authors: Weber Hugues , Breton Arnaud , Cyteval Catherine , Millet Ingrid , Girard Mehdi , Lonjon Nicolas , Capdevila Xavier , Charbit Jonathan
Published: May 2021

BACKGROUND

Our aim was to describe the characteristics of vertebral fractures, the presence of associated injuries, and clinical status within the first days in a severe trauma population.

METHODS

All patients with severe trauma admitted to our level 1 trauma center between January 2015 and December 2018 with a vertebral fracture were analyzed retrospectively. The fractures were determined by the AO Spine classification as stable (A0, A1, and A2 types) or unstable (A3, A4, B, and C types). Clinical status was defined as stable, intermediate, or unstable based on clinicobiological parameters and anatomic injuries. Severe extraspinal injuries and emergent procedures were studied. Three groups were compared: stable fracture, unstable fracture, and spinal cord injury (SCI) group.

RESULTS

A total of 425 patients were included (mean ± SD age, 43.8 ± 19.6 years; median Injury Severity Score, 22 [interquartile range, 17–34]; 72% male); 72 (17%) in the SCI group, 116 (27%) in the unstable fracture group, and 237 (56%) in the stable fracture group; 62% (95% confidence interval [CI], 57–67%) had not a stable clinical status on admission (unstable, 30%; intermediate, 32%), regardless of the group (p = 0.38). This decreased to 31% (95% CI, 27–35%) on day 3 and 23% (95% CI, 19–27%) on day 5, regardless of the group (p = 0.27 and p = 0.25). Progression toward stable clinical status between D1 and D5 was 63% (95% CI, 58–68%) overall but was statistically lower in the SCI group. Severe extraspinal injuries (85% [95% CI, 82–89%]) and extraspinal emergent procedures (56% [95% CI, 52–61%]) were comparable between the three groups. Only abdominal injuries and hemostatic procedures significantly differed significantly (p = 0.003 and p = 0.009).

CONCLUSION

More than the half of the patients with severe trauma had altered initial clinical status or severe extraspinal injuries that were not compatible with safe early surgical management for the vertebral fracture. These observations were independent of the stability of the fracture or the presence of an SCI.

LEVEL OF EVIDENCE

Prognostic and epidemiological, level III.
Dose-dependent association between blood transfusion and nosocomial infections in trauma patients: A secondary analysis of patients from the PAMPer trial
Authors: Ladhani Husayn A. , Ho Vanessa P. , Charbonnet C. Clare , Sperry Jason L. , Guyette Francis X. , Brown Joshua B. , Daley Brian J. , Miller Richard S. , Harbrecht Brian G. , Phelan Herb A. , Claridge Jeffrey A.
Published: May 2021

BACKGROUND

The Prehospital Air Medical Plasma (PAMPer) trial demonstrated a survival benefit to trauma patients who received thawed plasma as part of early resuscitation. The objective of our study was to examine the association between blood transfusion and nosocomial infections among trauma patients who participated in the PAMPer trial. We hypothesized that transfusion of blood products will be associated with the development of nosocomial infections in a dose-dependent fashion.

METHODS

We performed a secondary analysis of prospectively collected data of patients in the PAMPer trial with hospital length of stay of at least 3 days. Demographics, injury characteristics, and number of blood products transfused were obtained to evaluate outcomes. Bivariate analysis was performed to identify differences between patients with and without nosocomial infections. Two logistic regression models were created to evaluate the association between nosocomial infections and (1) any transfusion of blood products, and (2) quantity of blood products. Both models were adjusted for age, sex, and Injury Severity Score.

RESULTS

A total of 399 patients were included: age, 46 years (interquartile range, 29–59 years); Injury Severity Score, 22 (interquartile range, 12–29); 73% male; 80% blunt mechanism; and 40 (10%) deaths. Ninety-three (27%) developed nosocomial infections, including pneumonia (n = 67), bloodstream infections (n = 14), catheter-associated urinary tract infection (n = 10), skin and soft tissue infection (n = 8), Clostridium difficile colitis (n = 7), empyema (n = 6), and complicated intra-abdominal infections (n = 3). Nearly 80% (n = 307) of patients received packed red blood cells (PRBCs); 12% received cryoprecipitate, 69% received plasma, and 27% received platelets. Patients who received any PRBCs had more than a twofold increase in nosocomial infections (odds ratio, 2.15; 95% confidence interval, 1.01–4.58; p = 0.047). The number of PRBCs given was also associated with the development of nosocomial infection (odds ratio, 1.10; 95% confidence interval, 1.05–1.16; p < 0.001).

CONCLUSION

Trauma patients in the PAMPer trial who received a transfusion of at least 1 U of PRBCs incurred a twofold increased risk of nosocomial infection, and the risk of infection was dose dependent.

LEVEL OF EVIDENCE

Therapeutic/care management, level IV.
Critical traumatic brain injury is associated with worse coagulopathy
Authors: Cucher Daniel , Harmon Laura , Myer Brian , Ngyuen Andrew , Rankin Timothy , Cook Alan , Hu Charles , Tesoriero Ronald , Scalea Thomas , Stein Deborah
Published: May 2021

Objectives

As thromboelastography (TEG) becomes the standard of care in patients with hemorrhagic shock (HS), an association between concomitant traumatic brain injury (TBI) and coagulopathy by TEG parameters is not well understood and is thus investigated.

Methods

Retrospective analysis of trauma registry data at a single level 1 trauma center of 772 patients admitted with head Abbreviated Injury Scale (AIS) score of 3 and TEG studies between 2014 and 2017. Patients were stratified to moderate-severe TBI by head AIS scores of 3 and 4 (435 patients) and critical TBI by head AIS score of 5 (328 patients). Hemorrhagic shock was defined by base deficit of 4 or shock index of 0.9. Statistical analysis with unpaired t tests compared patients with critical TBI with patients with moderate-severe TBI, and patients were grouped by presence or absence of HS. A comparison of TBI data with conventional coagulation studies was also evaluated.

Results

In the setting of HS, critical TBI versus moderate-severe TBI was associated with longer R time (p = 0.004), longer K time (p < 0.05), less acute angle (p = 0.001), and lower clot strength and stability (maximum amplitude [MA]) (p = 0.01). Worse TBI did not correlate with increased fibrinolysis by clot lysis measured by the percentage decrease in amplitude at 30 minutes after MA (p = 0.3). Prothrombin time and international normalized ratio failed to demonstrate more severe coagulopathy, while partial thromboplastin time was found to correlate with severity of TBI (p = 0.01). In patients with critical TBI, the presence of HS correlated with a statistically significant worsening of all parameters (p < 0.05) except for clot lysis measured by the percentage decrease in amplitude at 30 minutes after MA (LY-30).

Conclusion

Thromboelastography demonstrates that, with and without hemorrhagic shock, critical TBI correlates with a significant worsening of traumatic coagulopathy in comparison with moderate/severe TBI. In HS, critical TBI correlates with impaired clot initiation, impaired clot kinetics, and impaired platelet-associated clot strength and stability versus parameters found in moderate-severe TBI. Hemorrhagic shock correlates with worse traumatic coagulopathy in all evaluated patient groups with TBI. Conventional coagulation studies underestimate TBI-associated coagulopathy. Traumatic brain injury–associated coagulopathy is not associated with fibrinolysis.

LEVEL OF EVIDENCE

Prognostic/epidemiological, level IV; prognostic/epidemiological, level III.
Use of regional analgesia and risk of delirium in older adults with multiple rib fractures: An Eastern Association for the Surgery of Trauma multicenter study
Authors: O’Connell Kathleen M. , Patel Kushang V. , Powelson Elisabeth , Robinson Bryce R.H. , Boyle Kelly , Peschman Jacob , Blocher-Smith Ethan C. , Jacobson Lewis , Leavitt Justin , McCrum Marta L. , Ballou Jessica , Brasel Karen J. , Judge Joshua , Greenberg Shannon , Mukherjee Kaushik , Qiu Qian , Vavilala Monica S. , Rivara Frederick , Arbabi Saman
Published: May 2021

BACKGROUND

Single-center data demonstrates that regional analgesia (RA) techniques are associated with reduced risk of delirium in older patients with multiple rib fractures. We hypothesized that a similar effect between RA and delirium would be identified in a larger cohort of patients from multiple level I trauma centers.

METHODS

Retrospective data from seven level I trauma centers were collected for intensive care unit (ICU) patients 65 years or older with ≥3 rib fractures from January 2012 to December 2016. Those with a head and/or spine injury Abbreviated Injury Scale (AIS) score of ≥ 3 or a history of dementia were excluded. Delirium was defined as one positive Confusion Assessment Method for the Intensive Care Unit score in the first 7 days of ICU care. Poisson regression with robust standard errors was used to determine the association of RA (thoracic epidural or paravertebral catheter) with delirium incidence.

RESULTS

Data of 574 patients with a median age of 75 years (interquartile range [IQR], 69–83), Injury Severity Score of 14 (IQR, 11–18), and ICU length of stay of 3 days (IQR, 2–6 days) were analyzed. Among the patients, 38.9% were women, 15.3% were non-White, and 31.4% required a chest tube. Regional analgesia was used in 19.3% patients. Patient characteristics did not differ by RA use; however, patients with RA had more severe chest injury (chest AIS, flail segment, hemopneumothorax, thoracostomy tube). In univariate analysis, there was no difference in the likelihood of delirium between the RA and no RA groups (18.9% vs. 23.8% p = 0.28). After adjusting for age, sex, Injury Severity Score, maximum chest AIS, thoracostomy tube, ICU length of stay, and trauma center, RA was associated with reduced risk of delirium (incident rate ratio [IRR], 0.65; 95% confidence interval [CI], 0.44–0.94) but not with in-hospital mortality (IRR, 0.42; 95% CI, 0.14–1.26) or respiratory complications (IRR, 0.70; 95% CI, 0.42–1.16).

CONCLUSION

In this multicenter cohort of injured older adults with multiple rib fractures, RA use was associated with a 35% lower risk of delirium. Further studies are needed to standardize protocols for optimal pain management and prevention of delirium in older adults with severe thoracic injury.

LEVEL OF EVIDENCE

Therapeutic, level IV; Epidemiologic, level III.
Preventing postnatal depression: a causal mediation analysis of a 20-year preconception cohort
Authors: Spry Elizabeth A. , Moreno-Betancur Margarita , Middleton Melissa , Howard Louise M. , Brown Stephanie J. , Molyneaux Emma , Greenwood Christopher J. , Letcher Primrose , Macdonald Jacqui A. , Thomson Kimberly C. , Biden Ebony J. , Olsson Craig A. , Patton George C.
Published: May 2021

Postnatal depression (PND) is common and predicts a range of adverse maternal and offspring outcomes. PND rates are highest among women with persistent mental health problems before pregnancy, and antenatal healthcare provides ideal opportunity to intervene. We examined antenatal perceived social support as a potential intervention target in preventing PND symptoms among women with prior mental health problems. A total of 398 Australian women (600 pregnancies) were assessed repeatedly for mental health problems before pregnancy (ages 14–29 years, 1992–2006), and again during pregnancy, two months postpartum and one year postpartum (2006–2014). Causal mediation analysis found that intervention on perceived antenatal social support has the potential to reduce rates of PND symptoms by up to 3% (from 15 to 12%) in women with persistent preconception symptoms. Supplementary analyses found that the role of low antenatal social support was independent of concurrent antenatal depressive symptoms. Combined, these two factors mediated up to more than half of the association between preconception mental health problems and PND symptoms. Trialling dual interventions on antenatal depressive symptoms and perceived social support represents one promising strategy to prevent PND in women with persistent preconception symptoms. Interventions promoting mental health before pregnancy may yield an even greater reduction in PND symptoms by disrupting a developmental cascade of risks via these and other pathways.

This article is part of the theme issue ‘Multidisciplinary perspectives on social support and maternal–child health’.
Allelic Variation inHLA-DRB1is Associated with Development of Anti-Drug Antibodies in Cancer Patients Treated with Atezolizumab that are Neutralizingin Vitro
Authors: Hammer Christian , Ruppel Jane , Hunkapiller Julie , Mellman Ira , Quarmby Valerie
Published: May 2021

The treatment of diseases with biologic agents can result in the formation of anti-drug antibodies (ADA). The occurrence of ADA were reported for atezolizumab, an anti-PD-L1 monoclonal antibody widely used as immunotherapeutic treatment in cancer patients. Although drivers for ADA formation are unknown, a role for antigen presentation is likely, and variation in human leukocyte antigen (HLA) genes has been shown to be associated with occurrence of ADA for several biologics. Here, we performed an HLA-wide association study in 1,982 patients treated with atezolizumab across 8 clinical trials. On average, 29.8% of patients were ADA positive (N = 591, range of 13.5% -38.4%), and 14.6% of patients were positive for ADA that were neutralizingin vitro(NAb, N = 278, range of 6.4% - 21.9%). We found statistically significant associations between HLA class II alleles and ADA status. The top-associated alleles wereHLA-DRB1*01:01for all ADA (p = 3.4*10−5, odds ratio = 1.96), andHLA-DQA1*01:01when considering NAb only (p = 2.8 x 10−7, OR = 2.31). Both alleles occur together on a common HLA haplotype, and the ADA association was explained by the NAb subset. In conclusion, our study showed that HLA class II genotype contributes to the risk of developing ADA, and specifically NAb, in patients treated with atezolizumab, but suggests that genetic factors are not sufficient as clinically meaningful predictors.
Rapid implementation of cross-sectional study: Post-acute sequelae of SARS-CoV-2 (PASC) in a racially and ethnically diverse sample in Illinois
Authors: Mermelstein Robin J. , Aiyer Meenakshy , Canfield Christine , Chestek David , Cook Judith A. , Rios Marina Del , Diviak Kathleen R. , Ellison Angela M. , Gordon Howard S. , Illendula Sai Dheeraj , Kandula Manasa , Klein Jonathan D. , Larimer Karen , Lash James , Lin Janet , Loeb Jeffrey A. , Lynch Teresa J. , Musick Hugh , Novak Richard M. , Prendergast Heather M. , Krishnan Jerry A.
Published: May 2021

Little is known about the pattern and course of recovery following acute COVID-19. Increasing numbers of reports describe persistent illness following infection with SARS-COV-2, also known as Post-Acute Sequelae of SARS-CoV-2 (PASC). This report describes the methods and results of a multi-pronged strategy to rapidly identify and enroll, over a one week period in April 2021, a racially and ethnically diverse sample of individuals and to characterize PASC among a this diverse sample. Participants were recruited through community outreach, clinical registries, and research registries across four cities in Illinois to complete an online survey. We examined presence of symptoms among 246 individuals who were at least three months past testing positive for SARS-CoV-2. Respondents were 70% female; 48% Hispanic/Latinx; 18% Black, and 28% White. Most had mild illness (78% were not hospitalized), and 26% reported they had not yet returned to their usual health within 3 months of their diagnosis. The most prevalent symptoms persisting 3-months following COVID-19 diagnosis included fatigue (20%), difficulty thinking (19%), problems with taste or smell (15%), and muscle or body aches (15%). In a multivariable logistic regression model, older age (40-59 vs. 18-39 years: adjusted odds ratio [aOR] = 0.46 [95% confidence interval, 0.24 to 0.90]) and having been hospitalized with COVID-19 (vs. not hospitalized: aOR = 0.28 [0.12 to 0.64]) were independently associated with a lower likelihood of recovery within 3 months. Compromised health continued well beyond the acute phase of COVID-19 in our ethnically diverse sample, especially among older individuals and those who were hospitalized. The partnerships with community- and faith-based organizations developed for the current study offer the potential to broadly disseminate study findings and to further understand and mitigate underlying determinants of risk, severity, and duration of PASC.