Use of Computed Tomography Angiography to Predict Complications in Tibia Fractures: A Multicenter Retrospective Analysis.

OBJECTIVES: To assess the ability of computed tomography angiography identified infrapopliteal vascular injury to predict complications in tibia fractures that do not require vascular surgical intervention. DESIGN: Multicenter retrospective review. SETTING: Six Level I trauma centers. PATIENTS AND INTERVENTION: Two hundred seventy-four patients with tibia fractures (OTA/AO 42 or 43) who underwent computed tomography angiography maintained a clinically perfused foot not requiring vascular surgical intervention and were treated with an intramedullary nail. Patients were grouped by the number of vessels below the trifurcation that were injured. MAIN OUTCOME MEASUREMENTS: Rates of superficial and deep infection, amputation, unplanned reoperation to promote bone healing (nonunion), and any unplanned reoperation. RESULTS: There were 142 fractures in the control (no-injury) group, 87 in the one-vessel injury group, and 45 in the two-vessel injury group. Average follow-up was 2 years. Significantly higher rates of nerve injury and flap coverage after wound breakdown were observed in the two-vessel injury group. The two-vessel injury group had higher rates of deep infection (35.6% vs. 16.9%, P = 0.030) and unplanned reoperation to promote bone healing (44.4% vs. 23.9%, P = 0.019) compared with controls, as well as increased rates of any unplanned reoperation compared with control and one-vessel injury groups (71.1% vs. 39.4% and 51.7%, P < 0.001), respectively. There were no significant differences in rates of superficial infection or amputation. CONCLUSIONS: Tibia fractures with two-vessel injuries were associated with higher rates of deep infection and unplanned reoperation to promote bone healing compared with those without vascular injury, as well as increased rates of any unplanned reoperation compared with controls and fractures with one-vessel injury. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Exposure of the Calcaneus in the Sinus Tarsi Approach Versus the Lateral Extensile Approach: A Cadaveric Study.

BACKGROUND: The lateral extensile approach (LEA) is an operative approach for calcaneal fractures. High rates of wound complications have led to alternative approaches such as the sinus tarsi approach to grow in popularity. The LEA affords substantial visualization of the calcaneus. This visualization has never been compared in a quantitative manner with the sinus tarsi approach (STA). We aim to quantify the calcaneal visualization afforded by STA and LEA. METHODS: Seven pair-matched, fresh-frozen, below-knee cadaver extremities were included. For each pair, one side received an LEA and the other side received an STA. RESULTS: There were no statistically significant differences in the articular surfaces accessible between the 2 approaches. The total calcaneal surface area accessible was 3107.08 mm2 for LEA and 1444.19 mm2 for STA (P = .02). The LEA allowed better exposure to the lateral wall (P = .01) and the dorsal tuberosity of the calcaneus (P = .04). CONCLUSION: The STA allows for equivalent articular surface exposure when compared with the LEA. Although LEA allows for greater exposure of the lateral wall and dorsal tuberosity, direct visualization of these structures may not warrant the higher risk of wound complications. Surgeons should consider these differences when choosing an operative approach in the treatment of calcaneal fractures.Level III.

Association of Mortality and Charlson Comorbidity Index in Surgical Spinal Trauma Patients at a Level I Academic Center.

OBJECTIVES: The Charlson Comorbidity Index score (CCI) records the presence of comorbidities with various weights for a total score to estimate mortality within 1 year of hospital admission. Our study sought to assess the association of CCI with mortality rates of patients undergoing surgical intervention. STUDY DESIGN: Retrospective study. METHODS: Retrospective study of patients with surgical spinal trauma at a large academic level I trauma tertiary center from 2015 to 2018. Information collected included age, sex, American Society of Anesthesiologists physical status, body mass index, Charlson comorbidities, injury severity score, the presence of spinal cord injury, and mortality. Mortality was measured at 30 days, 90 days, and 1 year. Descriptive and bivariate analyses were completed. The results were significant at P < 0.05. RESULTS: The highest proportion of 1-year mortality was in the patients with cervical (11.3%) and thoracolumbar injuries (7.4%) (P = 0.002). Patients with low CCI had low 1-year mortality (1.7%). Patients with high CCI had high 1-year mortality (13.8%) (P < 0.001). A significant association existed between CCI and mortality at 30 days, 90 days, and 1 year (P < 0.001). Mortality was higher in patients with spinal cord injury (14/108; 13%) than in those without (11/232; 5%) (P = 0.021). No association existed between ISS and mortality (P = 0.26). DISCUSSION: The CCI was associated with a higher proportion of deaths at 30 days, 90 days, and 1 year. This association may help predict this unfortunate complication and guide the surgical team in formulating treatment plans and counseling patients and families regarding mortality associated with these injuries and the risks of surgical intervention.

Union Rates of Talar Neck Fractures With Substantial Bone Defects Treated With Autograft.

BACKGROUND: This study evaluated the union rate of talar neck fractures with substantial bone defects treated acutely with autologous tibial bone graft during primary osteosynthesis. METHODS: A case series at a level 1 trauma center was performed to identify consecutive patients who underwent operative fixation of talar neck fracture with autograft (Current Procedural Terminology codes 28445 and 20902) between 2015 and 2018. "Substantial bone defect" was defined as a gap greater than 5 mm in the sagittal plane and greater than one-third of width of the talar neck in the coronal plane. Postoperative foot computed tomographic (CT) scans were obtained for all patients. Primary outcome was union, and secondary outcomes were malunion, avascular necrosis (AVN), post-traumatic arthritis (PTA), and patient-reported outcomes (PROs). RESULTS: Twelve patients with 12 fractures were included in the series, with an average length of follow-up of 26 months (range: 7-55) The average age was 34 years (17-59), and the most common mechanism of injury was motor vehicle crash. The Hawkins classification of the fractures was 4 type II (2 type IIA and 2 type IIB) (33%) and 8 type III (67%). Four fractures (33%) were open fractures. Union was achieved in 11 patients (92%). There was 1 malunion (8%). AVN was identified on postoperative CT scans in 11 patients (92%). Three of these 11 eventually showed collapse. Ten patients (83%) had radiographic evidence of some degree of ankle PTA, and 12 patients (100%) had radiographic evidence of some degree of subtalar PTA. Average Patient-Reported Outcomes Measurement Information System-Short Form score was 37 (32-45) and average Foot and Ankle Ability Measure activities of daily living and sports subscale scores were, respectively, 61 (31-87) and 31 (0-71), respectively. Average visual analog scale score was 5 (0-10), and average Foot Function Index was 49 (7-89). SF-36 scores showed fair to poor outcomes in the majority of patients. CONCLUSION: In this relatively small series, tibial autograft in primary osteosynthesis of comminuted talar neck fractures with substantial bone defects is associated with excellent union rates and low malunion rates. Despite high union rates, secondary outcomes of AVN with or without collapse, ankle and subtalar PTA, and relatively low PROs were common. LEVEL OF EVIDENCE: Level IV, case series.

Prevalence, Bias, and Rank List Impact of Illegal Questions in Surgical Specialty Residency Interviews.

OBJECTIVE: The purpose of this study is to characterize illegal questions as defined by federal law and to assess their impact on applicants' rank lists across four surgical specialties. DESIGN: A survey was developed and sent to surgical specialty residency applicants. The survey asked demographics, the frequency of questions about age, gender, religion, sexual orientation, family status and impact on final rank list. Applicants were asked to respond anonymously based on their experience at all institutions at which they interviewed during the interview cycle. Results were compared by applicant specialty and gender. SETTING: A large university-affiliated academic medical center PARTICIPANTS: Survey was administered to 3854 applicants (comprising between 28.9% and 41.2% of applicants nationwide) to general surgery, orthopaedic surgery, urology, and otolaryngology residency programs at a single institution during the 2018 and 2019 cycles. A total of 1066 applicants completed the survey. RESULTS: A total of 789 (74.0%) of applicants reported being asked at least one illegal question during the interview process at any institution. Applicants to orthopaedic surgery programs were most likely to be asked illegal question (n = 315, 81.6%), and general surgery applicants were least likely to be asked illegal questions (n = 324, 66.8%, p < 0.001). Females were more likely than males to be asked about gender (n = 99, 26.3% vs. n = 18, 2.6%, p < 0.001) and plans for pregnancy (n = 78, 20.8% vs. n = 78, 11.4%, p < 0.001). 152 (19.4%). Applicants reported that being asked an illegal question lowered a program on their rank list. Female applicants were more likely to lower a program on their rank list as a result of an illegal question (n = 102, 35.4% vs. n = 50, 10.1%, p < 0.001). CONCLUSIONS: Illegal questions in surgical specialty residency interviews are common, vary by specialty and applicant gender, and lower programs on applicants' rank lists. This data should serve to inform larger and more inclusive studies in the future. Programs should focus on educating interviewers on illegal topics in an effort to minimize illegal topics that may alienate applicants and contribute to workplace discrimination.

Extended Antibiotic Coverage in the Management of Type II Open Fractures.

Background: Responsible antibiotic stewardship requires surgeons treating open fractures to use the narrowest appropriate antibiotic coverage possible to prevent infection. Because inter-observer agreement about the application of the Gustilo-Anderson open fracture classification is moderate at best, antibiotic selection can be overly aggressive. The purpose of this study was to evaluate the outcomes of Type II open fractures treated with gram-positive coverage only (GP) versus broad-spectrum antibiotic coverage (BS) with piperacillin-tazobactam (PT). Methods: A retrospective review of all Type II open fractures was performed at a single Level one trauma center over a 5-year period (2013-2017). All patients received prophylactic antibiotics on arrival on the basis of the best judgment of classification by the house officer on call. The final Gustilo-Anderson open fracture classification was assigned intra-operatively by the operating surgeon. Two groups were created, a GP antibiotic group (cefazolin and/or clindamycin) and a BS group (PT). A minimum of 3-month follow-up was required for inclusion. Patient demographics, cost of treatment, fracture-related infection (FRI) rates, and infecting bacteria were assessed. Results: The GP group contained 70 open fractures and the BS group contained 74 open fractures. Between the groups, there were no differences in age, sex, race, Body Mass Index, American Society of Anesthesiologists Class, or smoking status. There were no statistical differences in Injury Severity Score (ISS), fracture location, fixation method, or rates of staged management with external fixation. There was no difference in FRI rate between the GP and BS groups (8.6% versus 10.8%; p = 0.78). The bacteria responsible for FRI were similar in the GP and BS groups. The hospital charge for PT was 4.39 × the cost of cefazolin. Conclusions: The use of BS coverage in Type II open fractures does not result in a lower infection rate and adds significant cost to patient care. These data support the use of a GP-only antibiotic regimen for Type II open fractures.

Civilian Ballistic Tibia Shaft Fractures Compared With Blunt Tibia Shaft Fractures: Open or Closed?

OBJECTIVES: To identify a group of ballistic tibia fractures, report the outcomes of these fractures, and compare them with both closed and open tibia fractures sustained by blunt mechanisms. We hypothesized that ballistic tibia fractures and blunt open fractures would have similar outcomes. DESIGN: Retrospective cohort study. SETTING: A single Level-1 trauma center. PATIENTS/PARTICIPANTS: Adult patients presenting with ballistic (44), blunt closed (179), or blunt open (179) tibia fractures. INTERVENTION: Intramedullary stabilization of tibia fracture. MAIN OUTCOMES: Unplanned reoperation, soft tissue reconstruction, nonunion, compartment syndrome, and fracture-related infection. RESULTS: Compared with the blunt closed group, the ballistic fracture group required more operations (P < 0.01), had a higher occurrence of soft tissue reconstruction (P < 0.01), and higher incidence of compartment syndrome (P = 0.02). Ballistic and blunt closed groups did not significantly differ in rates of unplanned reoperation (P = 0.67), nonunion (11.4% vs. 4.5%, P = 0.08), or deep infection (9.1% vs. 5.6%, P = 0.49). In comparison to the blunt open group, the ballistic group required a similar number of operations (P = 0.12), had similar rates of unplanned reoperation (P = 0.10), soft tissue reconstruction (P = 0.56), nonunion (11.4% vs. 17.9%, P = 0.49), and fracture-related infection (9.1% vs. 10.1%, P = 1.0) but a higher incidence of compartment syndrome (15.9% vs. 5.0%, P = 0.02). CONCLUSIONS: Ballistic tibia fractures require more surgeries and have higher rates of soft tissue reconstruction than blunt closed fractures and seem to have outcomes similar to lower severity open fractures. We found a significantly higher rate of compartment syndrome in ballistic tibia fractures than both open and closed blunt fractures. When treating ballistic tibia fractures, surgeons should maintain a high level of suspicion for the development of compartment syndrome and counsel patients that ballistic tibia fractures seem to behave like an intermediate category between closed and open fractures sustained through blunt mechanisms. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

The 2017 Solar Eclipse: Implementing Enhanced Syndromic Surveillance on the Path of Totality in Kentucky.

OBJECTIVE: The 2017 solar eclipse was associated with mass gatherings in many of the 14 states along the path of totality. The Kentucky Department for Public Health implemented an enhanced syndromic surveillance system to detect increases in emergency department (ED) visits and other health care needs near Hopkinsville, Kentucky, where the point of greatest eclipse occurred. METHODS: EDs flagged visits of patients who participated in eclipse events from August 17-22. Data from 14 area emergency medical services and 26 first-aid stations were also monitored to detect health-related events occurring during the eclipse period. RESULTS: Forty-four potential eclipse event-related visits were identified, primarily injuries, gastrointestinal illness, and heat-related illness. First-aid stations and emergency medical services commonly attended to patients with pain and heat-related illness. CONCLUSIONS: Kentucky's experience during the eclipse demonstrated the value of patient visit flagging to describe the disease burden during a mass gathering and to investigate epidemiological links between cases. A close collaboration between public health authorities within and across jurisdictions, health information exchanges, hospitals, and other first-response care providers will optimize health surveillance activities before, during, and after mass gatherings.

Elective spine surgery with continuation of clopidogrel anti-platelet therapy: Experiences from the community.

PURPOSE: This retrospective study aimed to assess the feasibility of continuing clopidogrel therapy during the perioperative period in elective cervical and thoracolumbar surgery. METHODS: After IRB approval, medical records of patients requiring one or two-level surgery over a two-year period (2015-2017) while receiving clopidogrel were reviewed for relevant outcomes. Over the same period, a control group of patients not receiving clopidogrel perioperatively was formed. RESULT: In total, 136 patients were included: 37 clopidogrel and 99 control, with a mean age of 64.8 years. Between clopidogrel and control respectively, operative time was 86.7 min and 86.7 min (p = 0.620); blood loss was 127.0 cc and 117.5 cc (p = 0.480); drain output was 171.2 cc and 190.7 cc (p = 0.354); length of stay was 1.8 days and 1.5 days (p = 0.103). Two clopidogrel patients and 1 control patient had complications. Two clopidogrel patients and 1 control patient were readmitted within 30 days. CONCLUSIONS: Remaining on clopidogrel therapy during elective spine surgery results in no difference in operative time, blood loss, drain output, length of stay, or readmission. Precaution should be taken in cervical procedures as the drain output in clopidogrel patients was increased and complications in this region can be severe.

Primary Indicators to Systematically Monitor COVID-19 Mitigation and Response - Kentucky, May 19-July 15, 2020.

State and local health departments in the United States are using various indicators to identify differences in rates of reported coronavirus disease 2019 (COVID-19) and severe COVID-19 outcomes, including hospitalizations and deaths. To inform mitigation efforts, on May 19, 2020, the Kentucky Department for Public Health (KDPH) implemented a reporting system to monitor five indicators of state-level COVID-19 status to assess the ability to safely reopen: 1) composite syndromic surveillance data, 2) the number of new COVID-19 cases,* 3) the number of COVID-19-associated deaths,† 4) health care capacity data, and 5) public health capacity for contact tracing (contact tracing capacity). Using standardized methods, KDPH compiles an indicator monitoring report (IMR) to provide daily analysis of these five indicators, which are combined with publicly available data into a user-friendly composite status that KDPH and local policy makers use to assess state-level COVID-19 hazard status. During May 19-July 15, 2020, Kentucky reported 12,742 COVID-19 cases, and 299 COVID-19-related deaths (1). The mean composite state-level hazard status during May 19-July 15 was 2.5 (fair to moderate). IMR review led to county-level hotspot identification (identification of counties meeting criteria for temporal increases in number of cases and incidence) and facilitated collaboration among KDPH and local authorities on decisions regarding mitigation efforts. Kentucky's IMR might easily be adopted by state and local health departments in other jurisdictions to guide decision-making for COVID-19 mitigation, response, and reopening.

What Is the Prevalence of Burnout, Depression, and Substance Use Among Orthopaedic Surgery Residents and What Are the Risk Factors? A Collaborative Orthopaedic Educational Research Group Survey Study.

BACKGROUND: Burnout and depression among healthcare professionals and trainees remain alarmingly common. In 2009, 56% of orthopaedic surgery residents reported burnout. Alcohol and illicit drug use are potential exacerbating factors of burnout and depression; however, these have been scarcely studied in residency populations. QUESTIONS/PURPOSES: (1) What proportion of orthopaedic residents report symptoms of burnout and depression? (2) What factors are independently associated with an orthopaedic resident reporting emotional exhaustion, depersonalization, low personal accomplishment, and depression? (3) What proportion of orthopaedic residents report hazardous alcohol or drug use? (4) What factors are independently associated with an orthopaedic resident reporting hazardous alcohol or drug use? METHODS: We asked 164 orthopaedic surgery programs to have their residents participate in a 34-question internet-based, anonymous survey, 28% of which (46 of 164) agreed. The survey was distributed to all 1147 residents from these programs, and 58% (661 of 1147) of these completed the survey. The respondents were evenly distributed among training years. Eighty-three percent (551 of 661) were men, 15% (101 of 661) were women, and 1% (nine of 661) preferred not to provide their gender. The survey asked about demographics, educational debt, sleep and work habits, perceived peer or program support, and substance use, and validated instruments were used to assess burnout (abbreviated Maslach Burnout Inventory), depression (Patient Health Questionnaire-2), and hazardous alcohol use (Alcohol Use Disorder Identification Test-Consumption). The main outcome measures included overall burnout, emotional exhaustion, depersonalization, low personal accomplishment, depression, and hazardous alcohol and drug use. Using the variables gathered in the survey, we performed an exploratory analysis to identify significant associations for each of the outcomes, followed by a multivariable analysis. RESULTS: Burnout was reported by 52% (342 of 661) of residents. Thirteen percent of residents (83 of 656) had positive screening results for depression. Factors independently associated with high emotional exhaustion scores included early training year (odds ratio 1.15; 95% confidence interval, 1.01-1.32; p = 0.03) unmanageable work volume (OR 3.13; 95% CI, 1.45-6.67; p < 0.01), inability to attend health maintenance appointments (OR 3.23; 95% CI, 1.69-6.25; p < 0.01), lack of exercise (OR 1.69; 95% CI, 1.08-2.70; p = 0.02), and lack of program support (OR 3.33; 95% CI, 2.00-5.56; p < 0.01). Factors independently associated with depersonalization included early training year (OR 1.27; 95% CI, 1.12-1.41; p < 0.01), inability to attend health maintenance appointments (OR 2.70; 95% CI, 1.67-4.35; p < 0.01), and lack of co-resident support (OR 2.52; 95% CI, 1.52-4.18; p < 0.01). Low personal accomplishment was associated with a lack of co-resident support (OR 2.85; 95% CI, 1.54-5.28; p < 0.01) and lack of program support (OR 2.33; 95% CI, 1.32-4.00; p < 0.01). Factors associated with depression included exceeding duty hour restrictions (OR 2.50; 95% CI, 1.43-4.35; p < 0.01) and lack of program support (OR 3.85; 95% CI, 2.08-7.14; p < 0.01). Sixty-one percent of residents (403 of 656) met the criteria for hazardous alcohol use. Seven percent of residents (48 of 656) reported using recreational drugs in the previous year. Factors independently associated with hazardous alcohol use included being a man (OR 100; 95% CI, 35-289; p < 0.01), being Asian (OR 0.31; 95% CI, 0.17-0.56; p < 0.01), single or divorced marital status (OR 2.33; 95% CI, 1.47-3.68; p < 0.01), and more sleep per night (OR 1.92; 95% CI, 1.21-3.06; p < 0.01). Finally, single or divorced marital status was associated with drug use in the past year (OR 2.30; 95% CI, 1.26-4.18; p < 0.01). CONCLUSIONS: The lack of wellness among orthopaedic surgery residents is troubling, especially because most of the associated risk factors are potentially modifiable. Programs should capitalize on the modifiable elements to combat burnout and improve overall wellbeing. Programs should also educate residents on burnout, focus on work volume, protect access to health maintenance, nurture those in the early years of training, and remain acutely aware of the risk of substance abuse. Orthopaedic surgery trainees should strive to encourage peer support, cultivate personal responsibility, and advocate for themselves or peers when faced with challenges. At a minimum, programs and educational leaders should foster an environment in which admitting symptoms of burnout is not seen as a weakness or failure. LEVEL OF EVIDENCE: Level II, prognostic study.

Factors affecting emergency department visits, readmissions, and reoperations within 30 days of ankle fracture surgery- an institutional retrospective study.

INTRODUCTION: With the U.S. healthcare system focused on value of care, providers and hospitals are increasingly measured by factors that increase patient care and decrease healthcare cost. Early postoperative adverse events not only increase healthcare cost, but also illuminate areas of potential improvement in patient care. This large single institution study aims to delineate factors that may influence emergency department visits, admissions, and reoperations within 30 days of ankle fracture surgery. METHODS: This retrospective review of patients at a Level 1 trauma center evaluated 30-day outcomes after ankle fracture surgery over a 4-year period (2015-2018). A total of 596 patients were included in final analysis. The primary outcome measures assessed were emergency department (ED) visits within 30 days, unplanned readmissions within 30 days and unplanned return to the operating room (OR) within 30 days. Patient and injury characteristics were investigated as potential factors related to these 30-day outcomes. Multiple linear regression was used for outcomes. RESULTS: Forty-three (7.2%) patients visited the ED within thirty days, 30 (5.0%) patients were readmitted within thirty days, and 10 (1.7%) patients requiring reoperation within thirty days. Sex, insurance status, several comorbidities, smoking status, and fracture type/location were not found to be significantly related to 30-day events. Age less than 45 was a significant risk factor for returning to the ED within 30 days (RR 2.1, p = 0.016). Open fractures were more likely to require unplanned reoperation than closed fractures (RR 5.7, p<0.01). Fifty-four percent of ED visits were for postoperative pain, while 37% of ED visits and 60% of readmissions within 30 days were for issues unrelated to the ankle fracture. CONCLUSIONS: Age less than 45 years old was a risk factor for early ED visits, highlighting a potential "at-risk" population after ankle fracture surgery. Furthermore, many of the ED visits (37%) and readmissions (60%) were unrelated to the ankle fracture suggesting unnecessary healthcare utilization may be avoided with protocols that increase emphasis on reconditioning and optimization of comorbidities.

Accuracy of talonavicular injection using ultrasound versus anatomical landmark: a cadaver study.

BACKGROUND: Intra-articular injections have diagnostic and therapeutic roles in foot and ankle pathologies due to complex anatomy, small size, diverse bones, and joints with proximity in this region. Conventionally, these injections are carried out using anatomical landmark technique and/or fluoroscopic guidance. The small joint space and needle size make the injection challenging. Fluoroscopy is not readily available in the clinical setting; ultrasound-guidance for injections is therefore increasingly being used. We compared the accuracy of intra-articular talonavicular injections using the anatomical landmark technique versus the ultrasound-guided method. PURPOSE: To determine whether ultrasound guidance yields superior results in intra-articular injections of the talonavicular joint compared to injections using palpatory method guided by anatomical landmarks. MATERIAL AND METHODS: The feet of 10 cadaveric specimens were held in neutral position by an assistant while a fellowship-trained foot-ankle orthopedic surgeon injected 2 cc of radiopaque dye using anatomical landmarks and palpation method in five specimens and under ultrasound guidance in the remaining five. The needles were left in situ in all specimens and their placement was confirmed fluoroscopically. RESULTS: In all five specimens injected under ultrasound guidance, the needle was found to be in the joint, whereas all five injected by palpation only were out of the joint, with one in the naviculo-cuneiform joint, showing ultrasound guidance to significantly increase the accuracy of intra-articular injections in the talonavicular joint than palpatory method alone. CONCLUSION: Ultrasound-guided injections not only confirm correct needle placement, but also delineate any tendon and/or joint pathology simultaneously.

Noncovalent Interactions between Trimethylamine N-Oxide (TMAO), Urea, and Water.

Trimethylamine N-oxide (TMAO) and urea are two important osmolytes with their main significance to the biophysical field being in how they uniquely interact with proteins. Urea is a strong protein destabilizing agent, whereas TMAO is known to counteract urea's deleterious effects. The exact mechanisms by which TMAO stabilizes and urea destabilizes folded proteins continue to be debated in the literature. Although recent evidence has suggested that urea binds directly to amino acid side chains to make protein folding less thermodynamically favored, it has also been suggested that urea acts indirectly to denature proteins by destabilizing the surrounding hydrogen bonding water networks. Here, we elucidate the molecular level mechanism of TMAO's unique ability to counteract urea's destabilizing nature by comparing Raman spectroscopic frequency shifts to the results of electronic structure calculations of microsolvated molecular clusters. Experimental and computational data suggest that the addition of TMAO into an aqueous solution of urea induces blue shifts in urea's H-N-H symmetric bending modes, which is evidence for direct interactions between the two cosolvents.

Female Adolescent With Quadricuspid Aortic Valve.

Quadricuspid aortic valve is a rare congenital heart defect. The authors present a case of this anomaly in a young, asymptomatic adolescent who presented to the echocardiography laboratory for further evaluation of a cardiac murmur detected on routine physical examination. Imaging revealed a quadricuspid aortic valve with aortic regurgitation. This case highlights the importance of auscultation in detecting cardiac abnormalities.