Lower Extremity Vascular Injury in the Pediatric Trauma Patient: Management and Outcomes at an Adult Level I Trauma Center.

BACKGROUND: Traumatic vascular injuries of the lower extremity in the pediatric population are uncommon but can result in significant morbidity. The objective of this study is to demonstrate our experience with these injuries by describing patterns of traumatic vascular injury, the initial management, and data regarding early outcomes. METHODS: In total, 506 patients presented with lower extremity vascular injury between January 1, 2009 and January 1, 2021 to Grady Memorial Hospital, an urban, adult Level I trauma center in Atlanta, Georgia. Thirty-two of the 506 patients were aged less than 18 years and were evaluated for a total of 47 lower extremity vascular injuries. To fully elucidate the injury patterns and clinical course in this population, we examined patient demographics, mechanism of injury, type of vessel injured, surgical repair performed, and early outcomes and complications. RESULTS: The median (interquartile range) age was 16 (2) years (range, 3-17 years), and the majority were male (n = 29, 90.6%). Of the vascular injuries identified, 28 were arterial and 19 were venous. Of these injuries, 14 patients had combined arterial-venous injuries. The majority of injuries were the result of a penetrating injury (n = 28, 87.5%), and of these, all but 2 were attributed to gunshot wounds. Twenty-seven vascular interventions were performed by nonpediatric surgeons: 11 by trauma surgeons, 13 by vascular surgeons, 2 by orthopedic surgeons, and 1 by an interventional radiologist. Two patients required amputation: 1 during the index admission and 1 delayed at 3 months. Overall survival was 96.9%. CONCLUSIONS: Vascular injuries as the result of trauma at any age often require early intervention, and we believe that these injuries in the pediatric population can be safely managed in adult trauma centers with a multidisciplinary team composed of trauma, vascular, and orthopedic surgeons with the potential to decrease associated morbidity and mortality from these injuries.

Pathogen Surveillance for Acute Infectious Conjunctivitis.

Importance: Acute infectious conjunctivitis is a common ocular condition with major public health consequences. Objective: To assess regional variations and microbial etiologies of acute infectious conjunctivitis to guide treatment. Design, Setting, and Participants: In this cross-sectional study, patients with presumed acute infectious conjunctivitis were enrolled in the study at 5 sites (Honolulu, Hawaii; Los Angeles, San Francisco, and San Diego, California; and Petah-Tikva, Israel) from March 2021 to March 2023. Patients with allergic or toxic conjunctivitis were excluded. Main Outcomes and Measures: Pathogens were identified by unbiased RNA deep sequencing. Results: In all, 52 patients (mean [range] age, 48 [7-80] years; 31 females [60%]) were enrolled at 5 sites (6 patients from Honolulu, 9 from San Diego, 11 from Los Angeles, 13 from San Francisco, and 13 from Petah-Tikva). RNA deep sequencing detected human adenovirus species D in one-quarter of patients (13 of 52). A wide range of pathogens, including human coronavirus 229E, SARS-CoV-2, and herpes simplex virus type 1, was also identified, as well as several bacteria and fungi. Moreover, 62% (32 of 52) of patients presented with purulent discharge, while only 8% (4 of 52) of patients had confirmed bacterial pathogens. Conclusion and Relevance: In this cross-sectional study, pathogens associated with acute infectious conjunctivitis varied between all 5 sites in the US and Israel. Purulent discharge was a common presenting sign in this study, with a low specificity for bacteria-associated conjunctivitis, suggesting that further diagnostic workup may be necessary to inform antibiotic stewardship. Additional research on cost-effectiveness of using RNA deep sequencing is needed to ascertain whether it is better to monitor patients clinically until resolution of disease.

Diabetic Soft Tissue Infections.

Diabetes is a systemic illness that can cause a broad range of physiologic effects. Infection rates and wound healing are both affected through multiple mechanisms. Other physiologic changes increase risk for wounds as well as complex soft tissue infections ranging from simple cellulitis to necrotizing soft tissue infections. Clinicians and surgeons need to have a low index of suspicion for severe infection in a patient presenting with diabetes, and even more so in patients with uncontrolled diabetes.

Blunt Traumatic Abdominal Wall Hernias: An Indicator for Emergent Laparotomy?

BACKGROUND: Traumatic abdominal wall hernias (TAWH) are relatively uncommon; however, the shearing force that results in fascial disruption could indicate an increased risk of visceral injury. The aim of our study was to evaluate whether the presence of a TAWH was associated with intra-abdominal injury requiring emergent laparotomy. METHODS: The trauma registry was queried over an 8-year period (7/2012-7/2020) for adult patients with blunt thoracoabdominal trauma diagnosed with a TAWH. Those patients who were identified with a TAWH and greater than 15 years of age were included in the study. Demographics, mechanism of injury, ISS, BMI, length of stay, TAWH size, type of TAWH repair, and outcomes were analyzed. RESULTS: Overall, 38,749 trauma patients were admitted over the study period, of which 64 (.17%) had a TAWH. Patients were commonly male (n = 42, 65.6%); the median age was 39 years (range 16-79 years) and a mean ISS of 21. Twenty-eight percent had a clinical seatbelt sign. Twenty-seven (42.2%) went emergently to the operating room, the majority for perforated viscus requiring bowel resection (n = 16, 25.0%), and 6 patients (9.4%) who were initially managed nonoperatively underwent delayed laparotomy. Average ventilator days was 14 days, with a mean ICU LOS of 14 days and mean hospital LOS of 18 days. About half of the hernias were repaired at the index operation, 6 of which were repaired primarily and 10 with mesh. CONCLUSION: The presence of a TAWH alone was an indication for immediate laparotomy to evaluate for intra-abdominal injury. In the absence of other indications for exploration, nonoperative management may be safe.

Reoperation rates for stress urinary incontinence and pelvic organ prolapse in women after undergoing Mid-Urethral sling with or without concomitant colporrhaphy in academic centers within the United States.

In this study, the rates of reoperation for stress urinary incontinence (SUI) and pelvic organ prolapse (POP) in women who underwent a mid-urethral sling (MUS) with or without concurrent colporrhaphy were evaluated. An academic faculty practice consortium database was used to identify a cohort of patients treated surgically for SUI with or without concurrent POP repair (apical, anterior, posterior, or a combination of the three) with or without hysterectomy between 2009 and 2011. A total of 20,484 patients matched the criteria. Of patients who underwent a MUS, 7.2% underwent secondary surgery, with a higher rate of 8.6% associated with those who underwent concurrent prolapse repair (Apical repair HR 1.84, p < .01; Anterior compartment repair HR 1.47, p < .01). Concurrent hysterectomy was associated with a lower hazard of secondary prolapse surgery (HR 0.48; p < .01) if the initial surgery involved a complete POP repair. Prolapse mesh repair resulted in a higher hazard of additional surgery (HR 1.43, p < .01). Medicaid insurance was also associated with an increased hazard ratio compared to commercial insurance for secondary surgery (HR 1.32, p < .01). For women undergoing MUS with complete prolapse repair, concurrent hysterectomy is associated with lower secondary surgery rates. Concurrent prolapse repair with mesh is associated with higher secondary surgery rates.Synopsis: For women undergoing MUS (mid-urethral sling) with complete prolapse repair, concurrent hysterectomy is associated with lower secondary surgery rates. Concurrent prolapse repair with mesh is associated with higher secondary surgery rates.Impact StatementWhat is already known on this subject? Stress urinary incontinence (SUI) and pelvic organ prolapse (POP) can present at the same time and negatively impact patients' quality of life. There is little data regarding reoperation rates for patients who undergo both MUS and colporrhaphy in one setting.What do the results of this study add? This study found that patients who undergo concurrent MUS (mid-urethral sling) and complete POP repair with the addition of hysterectomy had a lower risk of secondary surgery.What are the implications of these findings for clinical practice and/or further research? Our data can be used by surgeons to counsel patients on the risks of re-operation for SUI for those who would like to undergo concurrent POP repair with or without hysterectomy.

Risk Factors for Hospital-Acquired Pressure Injury in Adult Critical Care Patients.

BACKGROUND: Accurately measuring the risk of pressure injury remains the most important step for effective prevention and intervention. Relative contributions of risk factors for the incidence of pressure injury in adult critical care patients are not well understood. OBJECTIVE: To develop and validate a model to identify risk factors associated with hospital-acquired pressure injuries among adult critical care patients. METHODS: This retrospective cohort study included 23 806 adult patients (28 480 encounters) with an intensive care unit stay at an academic quaternary care center. Patient encounters were randomly split (7:3) into training and validation sets. The training set was used to develop a multivariable logistic regression model using the least absolute shrinkage and selection operator method. The model's performance was evaluated with the validation set. RESULTS: Independent risk factors identified by logistic regression were length of hospital stay, preexisting diabetes, preexisting renal failure, maximum arterial carbon dioxide pressure, minimum arterial oxygen pressure, hypotension, gastrointestinal bleeding, cellulitis, and minimum Braden Scale score of 14 or less. On validation, the model differentiated between patients with and without pressure injury, with area under the receiver operating characteristic curve of 0.85, and performed better than a model with Braden Scale score alone (P < .001). CONCLUSIONS: A model that identified risk factors for hospital-acquired pressure injury among adult critical care patients was developed and validated using a large data set of clinical variables. This model may aid in selecting high-risk patients for focused interventions to prevent formation of hospital-acquired pressure injuries.

Management of male sexual dysfunction after cancer treatment.

BACKGROUND: With an increase in the number of cancer survivors each year, male sexual dysfunction becomes an important topic for discussion between patients and providers who treat cancer. The aim of this article is to review types and mechanisms of sexual dysfunction after cancer therapy and discuss treatment options. METHODS: Contemporary concepts regarding male sexual dysfunction after cancer treatment are reviewed and translated for clinical utility. FINDINGS: To optimize recovery of erectile capacity after erectile dysfunction causing cancer treatments, a penile rehabilitation protocol involving phosphodiesterase inhibitors, vacuum erection device, intra corporal injections, or a combination is likely to provide some degree of clinically significant benefit. Treating hypogonadism post cancer treatment depends on the type of cancer that has been treated and patient comorbidities. Anejaculation after cancer treatments is typically not successfully or reliably treated due to the mechanism and severity of sympathetic nerve injury. Semen cryopreservation prior to cancer treatments that may injure nerve fibers essential for the ejaculatory response is highly recommended. CONCLUSION: Management of post cancer treatment sexual dysfunction requires identification of this problem and referral to a specialist if necessary. There are several management options available that can greatly enhance quality of life in this often overlooked aspect of post cancer treatment care.

Dynamic Risk Prediction for Hospital-Acquired Pressure Injury in Adult Critical Care Patients.

Accurately measuring the risk of pressure injury remains the most important step for effective prevention and intervention. Time-dependent risk factors for pressure injury development in the adult intensive care unit setting are not well understood. OBJECTIVES: To develop and validate a dynamic risk prediction model to estimate the risk of developing a hospital-acquired pressure injury among adult ICU patients. DESIGN: ICU admission data were split into training and validation sets. With death as a competing event, both static and dynamic Fine-Gray models were developed to predict hospital-acquired pressure injury development less than 24, 72, and 168 hours postadmission. Model performance was evaluated using Wolbers' concordance index, Brier score, net reclassification improvement, and integrated discrimination improvement. SETTING AND PARTICIPANTS: We performed a retrospective cohort study of ICU patients in a tertiary care hospital located in San Francisco, CA, from November 2013 to August 2017. MAIN OUTCOMES AND MEASURES: Data were extracted from electronic medical records of 18,019 ICU patients (age ≥ 18 yr; 21,220 encounters). Record of hospital-acquired pressure injury data was captured in our institution's incident reporting system. The information is periodically reviewed by our wound care team. Presence of hospital-acquired pressure injury during an encounter and hospital-acquired pressure injury diagnosis date were provided. RESULTS: The dynamic model predicting hospital-acquired pressure injury more than 24 hours postadmission, including predictors age, body mass index, lactate serum, Braden scale score, and use of vasopressor and antifungal medications, had adequate discrimination ability within 6 days from time of prediction (c = 0.73). All dynamic models produced more accurate risk estimates than static models within 26 days postadmission. There were no significant differences in Brier scores between dynamic and static models. CONCLUSIONS AND RELEVANCE: A dynamic risk prediction model predicting hospital-acquired pressure injury development less than 24 hours postadmission in ICU patients for up to 7 days postadmission was developed and validated using a large dataset of clinical variables readily available in the electronic medical record.

Photoaffinity labelling strategies for mapping the small molecule-protein interactome.

Nearly all FDA approved drugs and bioactive small molecules exert their effects by binding to and modulating proteins. Consequently, understanding how small molecules interact with proteins at an molecular level is a central challenge of modern chemical biology and drug development. Complementary to structure-guided approaches, chemoproteomics has emerged as a method capable of high-throughput identification of proteins covalently bound by small molecules. To profile noncovalent interactions, established chemoproteomic workflows typically incorporate photoreactive moieties into small molecule probes, which enable trapping of small molecule-protein interactions (SMPIs). This strategy, termed photoaffinity labelling (PAL), has been utilized to profile an array of small molecule interactions, including for drugs, lipids, metabolites, and cofactors. Herein we describe the discovery of photocrosslinking chemistries, including a comparison of the strengths and limitations of implementation of each chemotype in chemoproteomic workflows. In addition, we highlight key examples where photoaffinity labelling has enabled target deconvolution and interaction site mapping.

Developing Virtual Reality Trauma Training Experiences Using 360-Degree Video: Tutorial.

Historically, medical trainees were educated in the hospital on real patients. Over the last decade, there has been a shift to practicing skills through simulations with mannequins or patient actors. Virtual reality (VR), and in particular, the use of 360-degree video and audio (cineVR), is the next-generation advancement in medical simulation that has novel applications to augment clinical skill practice, empathy building, and team training. In this paper, we describe methods to design and develop a cineVR medical education curriculum for trauma care training using real patient care scenarios at an urban, safety-net hospital and Level 1 trauma center. The purpose of this publication is to detail the process of finding a cineVR production partner; choosing the camera perspectives; maintaining patient, provider, and staff privacy; ensuring data security; executing the cineVR production process; and building the curriculum.

Low-Dose Naltrexone for Chronic Pain: Update and Systemic Review.

PURPOSE OF REVIEW: The purpose of this review is to evaluate and explain our current understanding of the clinical use of low-dose naltrexone in the treatment of chronic pain. RECENT FINDINGS: Recent pre-clinical uses and clinical studies further elucidate the use of low-dose naltrexone in the treatment of chronic pain. Low-dose naltrexone (LDN) has shown promise to reduce symptoms related to chronic pain conditions such as fibromyalgia, inflammatory bowel conditions, and multiple sclerosis. The mechanism of LDN appears to be modulation of neuro-inflammation, specifically, the modulation of the glial cells and release of inflammatory chemicals in the central nervous system. These effects appear to unique at low dosage compared to dosage for food and drug administration approved use for alcohol and opioid dependence. We review the evidence that LDN has shown more than promise and should be further investigated in clinical practice.

Buprenorphine for Chronic Pain: a Systemic Review.

PURPOSE OF REVIEW: The purpose of this review is to evaluate and explain our current understanding of the clinical use of buprenorphine in the treatment of chronic pain. RECENT FINDINGS: There has been few high-quality, unbiased studies performed on the use of buprenorphine in the treatment of chronic pain. Buprenorphine is an effective and safe analgesic that is tolerated at least as well, if not better, than other opioids. Given its safety and mechanistic advantages, the authors believe there is an important role for buprenorphine in the treatment of chronic pain severe enough to warrant the use of an opioid analgesic. Though data is lacking for superiority in chronic pain states, the other advantages of the molecule make it the preferential first-line opioid for around-the-clock pain in our practice.

HER2-Overexpressing Breast Cancers Amplify FGFR Signaling upon Acquisition of Resistance to Dual Therapeutic Blockade of HER2.

Purpose: Dual blockade of HER2 with trastuzumab and lapatinib or pertuzumab has been shown to be superior to single-agent trastuzumab. However, a significant fraction of HER2-overexpressing (HER2+) breast cancers escape from these drug combinations. In this study, we sought to discover the mechanisms of acquired resistance to the combination of lapatinib + trastuzumab.Experimental Design: HER2+ BT474 xenografts were treated with lapatinib + trastuzumab long-term until resistance developed. Potential mechanisms of acquired resistance were evaluated in lapatinib + trastuzumab-resistant (LTR) tumors by targeted capture next-generation sequencing. In vitro experiments were performed to corroborate these findings, and a novel drug combination was tested against LTR xenografts. Gene expression and copy-number analyses were performed to corroborate our findings in clinical samples.Results: LTR tumors exhibited an increase in FGF3/4/19 copy number, together with an increase in FGFR phosphorylation, marked stromal changes in the tumor microenvironment, and reduced tumor uptake of lapatinib. Stimulation of BT474 cells with FGF4 promoted resistance to lapatinib + trastuzumab in vitro Treatment with FGFR tyrosine kinase inhibitors reversed these changes and overcame resistance to lapatinib + trastuzumab. High expression of FGFR1 correlated with a statistically shorter progression-free survival in patients with HER2+ early breast cancer treated with adjuvant trastuzumab. Finally, FGFR1 and/or FGF3 gene amplification correlated with a lower pathologic complete response in patients with HER2+ early breast cancer treated with neoadjuvant anti-HER2 therapy.Conclusions: Amplification of FGFR signaling promotes resistance to HER2 inhibition, which can be diminished by the combination of HER2 and FGFR inhibitors. Clin Cancer Res; 23(15); 4323-34. ©2017 AACR.

A clinically feasible multiplex proteomic immunoassay as a novel functional diagnostic for pancreatic ductal adenocarcinoma.

To date, targeted therapy for pancreatic ductal adenocarcinoma (PDAC) remains largely unsuccessful in the clinic. Current genomics-based technologies are unable to reflect the quantitative, dynamic signaling changes in the tumor, and require larger tumor samples that are difficult to obtain in PDAC patients. Therefore, a highly sensitive functional tool that can reliably and comprehensively inform intra-tumoral signaling events is direly needed to guide treatment decision. We tested the utility of a highly sensitive proteomics-based functional diagnostic platform, Collaborative Enzyme Enhanced Reactive-immunoassay (CEERTM), on fine-needle aspiration (FNA) samples obtained from 102 patients with radiographically-evident pancreatic tumors. Two FNA passes were collected from each patient, hybridized to customized chips coated with an array of capture antibodies, and detected using two enzyme-conjugated antibodies which emit quantifiable signals. We demonstrate that this technique is highly sensitive in detecting total and phosphorylated forms of multiple signaling molecules in FNA specimens, with reasonable correlation of marker intensities between two different FNA passes. Notably, signals of several markers were significantly higher in PDAC compared to non-cancerous samples. In PDAC samples, we found high total c-Met signal to be associated with poor survival, and confirmed this finding using an independent PDAC tissue microarray.