Association of timing and agent for VTE prophylaxis in patients with severe traumatic brain injury on VTE, mortality, neurosurgical intervention, and discharge disposition.

BACKGROUND: Trauma patients are at increased risk for venous thromboembolism events (VTE). The decision of when to initiate VTE chemoprophylaxis (VTEP) and with what agent remains controversial in patients with severe traumatic brain injury (TBI). METHODS: This comparative effectiveness study evaluated the impact of timing and agent for VTEP on outcomes for patients with severe TBI (AIS Head = 3,4, or 5). Data was collected at 35 Level 1 and 2 trauma centers from January 1, 2017 to June 1, 2022. Patients were placed into analysis cohorts: No VTEP, low-molecular weight heparin (LMWH) ≤ 48 hours, LMWH>48 hours, Heparin≤48 hours, Heparin>48 hours. Propensity score matching accounting for patient factors and injury characteristics was used with logistic regression modeling to evaluate in-hospital mortality, VTE events, and discharge disposition. Neurosurgical intervention after initiation of VTEP was used to evaluate extension of intracranial hemorrhage. RESULTS: Of 12,879 patients, 32% had no VTEP, 36% LMWH, and 32% Heparin. Overall mortality was 8.3% and lowest among patients receiving LMWH≤48 hours (4.1%). VTE rates were lower with use of LMWH (1.6 vs 4.5%, OR 2.98, 95% CI 1.40-6.34, p = 0.005) without increasing mortality or neurosurgical interventions. VTE rates were lower with early prophylaxis (2.0 vs 3.5%, OR 1.76, 95% CI 1.15-2.71, p = 0.01) without increasing mortality (p = 1.0). Early VTEP was associated with more non-fatal intracranial operations (p < 0.001). However, patients undergoing neurosurgical intervention after VTEP initiation had no difference in rates of mortality, withdrawal of care, or unfavorable discharge disposition (p = 0.7, p = 0.1, p = 0.5). CONCLUSIONS: In patients with severe TBI, LMWH usage was associated with lower VTE incidence without increasing mortality or neurosurgical interventions. Initiation of VTEP≤48 hours decreased VTE incidence and increased non-fatal neurosurgical interventions without affecting mortality. LMWH is the preferred VTEP agent for severe TBI, and initiation ≤48 hours should be considered in relation to these risks and benefits. LEVEL OF EVIDENCE: Therapeutic/Care Management, Level III.

Efficacy of assisted partner services for people who inject drugs in Kenya to identify partners living with HIV and hepatitis C virus infection: a prospective cohort study.

BACKGROUND: People who inject drugs are at increased risk of both HIV and hepatitis C virus (HCV) infections but face barriers to testing and engagement in care. Assisted partner services are effective in locating people with HIV but are understudied among people who inject drugs. We assessed whether assisted partner services could be used to find, test for HIV and HCV infections, and link to care the partners of people who inject drugs in Kenya. METHODS: In this prospective study at eight sites offering harm-reduction services in Kenya, we enrolled people aged 18 years or older who inject drugs and were living with HIV (index participants) between Feb 27, 2018, and Nov 1, 2021. Index participants provided information about their sexual and injecting partners (ie, anyone with whom they had had sexual intercourse or injected drugs in the previous 3 years), and then community-embedded peer educators located partners and referred them for enrolment in the study (partner participants). All participants underwent testing for HCV infection, and partner participants also underwent HIV testing. Index and partner participants with HIV but who were not on antiretroviral therapy (ART) were linked with treatment services, and those positive for HCV were linked to treatment with direct-acting antivirals. We calculated the number of index participants whom we needed to interview to identify partner participants with HIV and HCV infection. FINDINGS: We enrolled 989 people living with HIV who inject drugs, who mentioned 4705 sexual or injecting partners. Of these 4705 partners, we enrolled 4597 participants, corresponding to 3323 unique individuals. 597 (18%) partner participants had HIV, of whom 506 (85%) already knew their status. 358 (71%) of those who knew they were HIV positive were virally suppressed. 393 (12%) partner participants were HCV antibody positive, 213 (54%) of whom had viraemia and 104 (26%) of whom knew their antibody status. 1·66 (95% CI 1·53-1·80) index participants had to be interviewed to identify a partner with HIV, and 4·24 (3·75-4·85) had to be interviewed to find a partner living with HIV who was unaware of their HIV status, not on ART, or not virally suppressed. To find a partner seropositive for HCV who did not know their antibody status, 3·47 (3·11-3·91) index participants needed to be interviewed. Among the 331 index and partner participants living with HIV who were not on ART at enrolment, 238 (72%) were taking ART at 6-month follow-up. No adverse events were attributed to study procedures. INTERPRETATION: Use of assisted partner services among people with HIV who inject drugs was safe and identified partners with HIV and HCV infections. Assisted partner services was associated with increased uptake of ART for both index participants and partners. FUNDING: US National Institutes of Health.

Characterizing Trauma Patients with Delays in Orthopaedic Process Measures.

INTRODUCTION: Early operative intervention in orthopaedic injuries is associated with decreased morbidity and mortality. Relevant process measures (e.g. femoral shaft fixation <24 hours) are used in trauma quality improvement programs to evaluate performance. Currently, there is no mechanism to account for patients who are unable to undergo surgical intervention (i.e. physiologically unstable). We characterized the factors associated with patients who did not meet these orthopaedic process measures. METHODS: A retrospective cohort study of patients from 35 ACS-COT verified Level 1 and Level 2 trauma centers was performed utilizing quality collaborative data (2017-2022). Inclusion criteria were adult patients (≥18 years), ISS ≥5, and a closed femoral shaft or open tibial shaft fracture classified via the Abbreviated Injury Scale version 2005 (AIS2005). Relevant factors (e.g. physiologic) associated with a procedural delay >24 hours were identified through a multivariable logistic regression and the effect of delay on inpatient outcomes was assessed. A sub-analysis characterized the rate of delay in "healthy patients". RESULTS: We identified 5,199 patients with a femoral shaft fracture and 87.5% had a fixation procedure, of which 31.8% had a delay, and 47.1% of those delayed were "healthy." There were 1,291 patients with an open tibial shaft fracture, 92.2% had fixation, 50.5% had an irrigation and debridement and 11.2% and 18.7% were delayed, respectively. High ISS, older age and multiple medical comorbidities were associated with a delay in femur fixation, and those delayed had a higher incidence of complications. CONCLUSIONS: There is a substantial incidence of surgical delays in some orthopaedic trauma process measures that are predicted by certain patient characteristics, and this is associated with an increased rate of complications. Understanding these factors associated with a surgical delay, and effectively accounting for them, is key if these process measures are to be used appropriately in quality improvement programs. LEVEL OF EVIDENCE: Level III; Therapeutic/Care Management.

Evidence of the Monopolar-Dipolar Crossover Regime: A Multiscale Study of Ferroelastic Domains by In Situ Microscopy Techniques.

The elastic interaction between kinks (and antikinks) within domain walls plays a pivotal role in shaping the domain structure, and their dynamics. In bulk materials, kinks interact as elastic monopoles, dependent on the distance between walls (d-1) and typically characterized by a rigid and straight domain configuration. In this work the evolution of the domain structure is investigated, as the sample size decreases, by the means of in situ heating microscopy techniques on free-standing samples. As the sample size decreases, a significant transformation is observed: domain walls exhibit pronounced curvature, accompanied by an increase in both domain wall and junction density. This transformation is attributed to the pronounced influence of kinks, inducing sample warping, where "dipole-dipole" interactions are dominant (d-2). Moreover, a critical thickness range that delineates a crossover between the monopolar and dipolar regimens is experimentally identified and corroborated by atomic simulations. These findings are relevant for in situ TEM studies and for the development of novel devices based on free-standing ferroic thin films and nanomaterials.

Financial toxicity part II: A practical guide to measuring and tracking long-term financial outcomes among acute care surgery patients.

ABSTRACT: Acute care surgery (ACS) patients are frequently faced with significant long-term recovery and financial implications that extend far beyond their hospitalization. While major injury and emergency general surgery (EGS) emergencies are often viewed solely as acute moments of crisis, the impact on patients can be lifelong. Financial outcomes after major injury or emergency surgery have only begun to be understood. The Healthcare Economics Committee from the American Association for the Surgery of Trauma previously published a conceptual overview of financial toxicity in ACS, highlighting the association between financial outcomes and long-term physical recovery. The aims of second-phase financial toxicity review by the Healthcare Economics Committee of the American Association for the Surgery of Trauma are to (1) understand the unique impact of financial toxicity on ACS patients; (2) delineate the current limitations surrounding measurement domains of financial toxicity in ACS; (3) explore the "when, what and how" of optimally capturing financial outcomes in ACS; and (4) delineate next steps for integration of these financial metrics in our long-term patient outcomes. As acute care surgeons, our patients' recovery is often contingent on equal parts physical, emotional, and financial recovery. The ACS community has an opportunity to impact long-term patient outcomes and well-being far beyond clinical recovery.

Burnout, Compassion Fatigue, and the Long Haul of Caring for Long COVID.

The current landscape of clinician burnout is prompting the need for our health care system to revise its approach toward complex conditions such as long coronavirus disease (COVID), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and other postinfectious fatiguing illnesses (PIFIs). We discuss our efforts here at Family Health Center of San Diego (FHCSD) to help share insight and glean perspective from clinicians who have participated in our Centers for Disease Control and Prevention (CDC)-funded 3-year continuing professional development initiative. The Long COVID and Fatiguing Illness Recovery Program uses multidisciplinary team-based case consultation and peer-to-peer sharing of emerging best and promising practices (ie, teleECHO [Extension for Community Healthcare Outcomes]) to support the management of complex cases associated with long COVID, ME/CFS, and other PIFIs. We believe that this perspective captures a key moment in the trajectory of postpandemic clinician burnout and prompts further reflection and action from the health care system to improve clinician- and patient-level outcomes related to the care of patients with postinfectious fatiguing illnesses.

Large-Scale Telemedicine Implementation for Outpatient Clinicians: Results From a Pandemic-Adapted Learning Collaborative.

Learning collaboratives are seldom used outside of health care quality improvement. We describe a condensed, 10-week learning collaborative ("Telemedicine Hack") that facilitated telemedicine implementation for outpatient clinicians early in the COVID-19 pandemic. Live attendance averaged 1688 participants per session. Of 1005 baseline survey respondents, 57% were clinicians with one-third identifying as from a racial/ethnic minoritized group. Practice characteristics included primary care (71%), rural settings (51%), and community health centers (28%). Of three surveys, a high of 438 (81%) of 540 clinicians had billed ≥1 video-based telemedicine visit. Our learning collaborative "sprint" is a promising model for scaling knowledge during emergencies and addressing health inequities.

Higher Rates Of Emergency Surgery, Serious Complications, And Readmissions In Primary Care Shortage Areas, 2015-19.

Primary care physicians are often the first to screen and identify patients with access-sensitive surgical conditions that should be treated electively. These conditions require surgery that is preferably planned (elective), but, when access is limited, treatment may be delayed and worsening symptoms lead to emergency surgery (for example, colectomy for cancer, abdominal aortic aneurysm repair, and incisional hernia repair). We evaluated the rates of elective versus emergency surgery for patients with three access-sensitive surgical conditions living in primary care Health Professional Shortage Areas during 2015-19. Medicare beneficiaries in more severe primary care shortage areas had higher rates of emergency surgery compared with rates in the least severe shortage areas (37.8 percent versus 29.9 percent). They were also more likely to have serious complications (14.9 percent versus 11.7 percent) and readmissions (15.7 percent versus 13.5 percent). When we accounted for areas with a shortage of surgeons, the findings were similar. Taken together, these findings suggest that residents of areas with greater primary care workforce shortages may also face challenges in accessing elective surgical care. As policy makers consider investing in Health Professional Shortage Areas, our findings underscore the importance of primary care access to a broader range of services.

Health Insurance Status and Unplanned Surgery for Access-Sensitive Surgical Conditions.

Importance: Access-sensitive surgical conditions, such as abdominal aortic aneurysm, ventral hernia, and colon cancer, are ideally treated with elective surgery, but when left untreated have a natural history requiring an unplanned operation. Patients' health insurance status may be a barrier to receiving timely elective care, which may be associated with higher rates of unplanned surgery and worse outcomes. Objective: To evaluate the association between patients' insurance status and rates of unplanned surgery for these 3 access-sensitive surgical conditions and postoperative outcomes. Design, Setting, and Participants: This cross-sectional cohort study examined a geographically broad patient sample from the Healthcare Cost and Utilization Project State Inpatient Databases, including data from 8 states (Arizona, Colorado, Florida, Kentucky, Maryland, North Carolina, Washington, and Wisconsin). Participants were younger than 65 years who underwent abdominal aortic aneurysm repair, ventral hernia repair, or colectomy for colon cancer between 2016 and 2020. Patients were stratified into groups by insurance status. Data were analyzed from June 1 to July 1, 2023. Exposure: Health insurance status (private insurance, Medicaid, or no insurance). Main Outcomes and Measures: The primary outcome was the rate of unplanned surgery for these 3 access-sensitive conditions. Secondary outcomes were rates of postoperative outcomes including inpatient mortality, any hospital complications, serious complications (a complication with a hospital length of stay longer than the 75th percentile for that procedure), and hospital length of stay. Results: The study included 146 609 patients (mean [SD] age, 50.9 [10.3] years; 73 871 females [50.4%]). A total of 89 018 patients (60.7%) underwent elective surgery while 57 591 (39.3%) underwent unplanned surgery. Unplanned surgery rates varied significantly across insurance types (33.14% for patients with private insurance, 51.46% for those with Medicaid, and 72.60% for those without insurance; P < .001). Compared with patients with private insurance, patients without insurance had higher rates of inpatient mortality (1.29% [95% CI, 1.04%-1.54%] vs 0.61% [0.57%-0.66%]; P < .001), higher rates of any complications (19.19% [95% CI, 18.33%-20.05%] vs 12.27% [95% CI, 12.07%-12.47%]; P < .001), and longer hospital stays (7.27 [95% CI, 7.09-7.44] days vs 5.56 [95% CI, 5.53-5.60] days, P < .001). Conclusions and Relevance: Findings of this cohort study suggest that uninsured patients more often undergo unplanned surgery for conditions that can be treated electively, with worse outcomes and longer hospital stays compared with their counterparts with private health insurance. As efforts are made to improve insurance coverage, tracking elective vs unplanned surgery rates for access-sensitive surgical conditions may be a useful measure to assess progress.

Discovery of a Cushing's syndrome protein kinase A mutant that biases signaling through type I AKAPs.

Adrenal Cushing's syndrome is a disease of cortisol hypersecretion often caused by mutations in protein kinase A catalytic subunit (PKAc). Using a personalized medicine screening platform, we discovered a Cushing's driver mutation, PKAc-W196G, in ~20% of patient samples analyzed. Proximity proteomics and photokinetic imaging reveal that PKAcW196G is unexpectedly distinct from other described Cushing's variants, exhibiting retained association with type I regulatory subunits (RI) and their corresponding A kinase anchoring proteins (AKAPs). Molecular dynamics simulations predict that substitution of tryptophan-196 with glycine creates a 653-cubic angstrom cleft between the catalytic core of PKAcW196G and type II regulatory subunits (RII), but only a 395-cubic angstrom cleft with RI. Endocrine measurements show that overexpression of RIα or redistribution of PKAcW196G via AKAP recruitment counteracts stress hormone overproduction. We conclude that a W196G mutation in the kinase catalytic core skews R subunit selectivity and biases AKAP association to drive Cushing's syndrome.

cAMP signaling: a remarkably regional affair.

Louis Pasteur once famously said 'in the fields of observation chance favors only the prepared mind'. Much of chance is being in the right place at the right time. This is particularly true in the crowded molecular environment of the cell where being in the right place is often more important than timing. Although Brownian motion argues that enzymes will eventually bump into substrates, this probability is greatly enhanced if both molecules reside in the same subcellular compartment. However, activation of cell signaling enzymes often requires the transmission of chemical signals from extracellular stimuli to intracellular sites of action. This review highlights new developments in our understanding of cAMP generation and the 3D utilization of this second messenger inside cells.

The invisible scars: Unseen financial complications worsen every aspect of long-term health in trauma survivors.

BACKGROUND: Trauma survivors are susceptible to experiencing financial toxicity (FT). Studies have shown the negative impact of FT on chronic illness outcomes. However, there is a notable lack of data on FT in the context of trauma. We aimed to better understand prevalence, risk factors, and impact of FT on trauma long-term outcomes. METHODS: Adult trauma patients with an Injury Severity Score (ISS) ≥9 treated at Level I trauma centers were interviewed 6 months to 14 months after discharge. Financial toxicity was considered positive if patients reported any of the following due to the injury: income loss, lack of care, newly applied/qualified for governmental assistance, new financial problems, or work loss. The Impact of FT on Patient Reported Outcome Measure Index System (PROMIS) health domains was investigated. RESULTS: Of 577 total patients, 44% (254/567) suffered some form of FT. In the adjusted model, older age (odds ratio [OR], 0.4; 95% confidence interval [95% CI], 0.2-0.81) and stronger social support networks (OR, 0.44; 95% CI, 0.26-0.74) were protective against FT. In contrast, having two or more comorbidities (OR, 1.81; 95% CI, 1.01-3.28), lower education levels (OR, 1.95; 95% CI, 95%, 1.26-3.03), and injury mechanisms, including road accidents (OR, 2.69; 95% CI, 1.51-4.77) and intentional injuries (OR, 4.31; 95% CI, 1.44-12.86) were associated with higher toxicity. No significant relationship was found with ISS, sex, or single-family household. Patients with FT had worse outcomes across all domains of health. There was a negative linear relationship between the severity of FT and worse mental and physical health scores. CONCLUSION: Financial toxicity is associated with long-term outcomes. Incorporating FT risk assessment into recovery care planning may help to identify patients most in need of mitigative interventions across the trauma care continuum to improve trauma recovery. Further investigations to better understand, define, and address FT in trauma care are warranted. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

Improving outcomes in emergency general surgery: Construct of a collaborative quality initiative.

BACKGROUND: Emergency general surgery conditions are common, costly, and highly morbid. The proportion of excess morbidity due to variation in health systems and processes of care is poorly understood. We constructed a collaborative quality initiative for emergency general surgery to investigate the emergency general surgery care provided and guide process improvements. METHODS: We collected data at 10 hospitals from July 2019 to December 2022. Five cohorts were defined: acute appendicitis, acute gallbladder disease, small bowel obstruction, emergency laparotomy, and overall aggregate. Processes and inpatient outcomes investigated included operative versus nonoperative management, mortality, morbidity (mortality and/or complication), readmissions, and length of stay. Multivariable risk adjustment accounted for variations in demographic, comorbid, anatomic, and disease traits. RESULTS: Of the 19,956 emergency general surgery patients, 56.8% were female and 82.8% were White, and the mean (SD) age was 53.3 (20.8) years. After accounting for patient and disease factors, the adjusted aggregate mortality rate was 3.5% (95% confidence interval [CI], 3.2-3.7), morbidity rate was 27.6% (95% CI, 27.0-28.3), and the readmission rate was 15.1% (95% CI, 14.6-15.6). Operative management varied between hospitals from 70.9% to 96.9% for acute appendicitis and 19.8% to 79.4% for small bowel obstruction. Significant differences in outcomes between hospitals were observed with high- and low-outlier performers identified after risk adjustment in the overall cohort for mortality, morbidity, and readmissions. The use of a Gastrografin challenge in patients with a small bowel obstruction ranged from 10.7% to 61.4% of patients. In patients who underwent initial nonoperative management of acute cholecystitis, 51.5% had a cholecystostomy tube placed. The cholecystostomy tube placement rate ranged from 23.5% to 62.1% across hospitals. CONCLUSION: A multihospital emergency general surgery collaborative reveals high morbidity with substantial variability in processes and outcomes among hospitals. A targeted collaborative quality improvement effort can identify outliers in emergency general surgery care and may provide a mechanism to optimize outcomes. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Recruitment of BAG2 to DNAJ-PKAc scaffolds promotes cell survival and resistance to drug-induced apoptosis in fibrolamellar carcinoma.

The DNAJ-PKAc fusion kinase is a defining feature of fibrolamellar carcinoma (FLC). FLC tumors are notoriously resistant to standard chemotherapies, with aberrant kinase activity assumed to be a contributing factor. By combining proximity proteomics, biochemical analyses, and live-cell photoactivation microscopy, we demonstrate that DNAJ-PKAc is not constrained by A-kinase anchoring proteins. Consequently, the fusion kinase phosphorylates a unique array of substrates, including proteins involved in translation and the anti-apoptotic factor Bcl-2-associated athanogene 2 (BAG2), a co-chaperone recruited to the fusion kinase through association with Hsp70. Tissue samples from patients with FLC exhibit increased levels of BAG2 in primary and metastatic tumors. Furthermore, drug studies implicate the DNAJ-PKAc/Hsp70/BAG2 axis in potentiating chemotherapeutic resistance. We find that the Bcl-2 inhibitor navitoclax enhances sensitivity to etoposide-induced apoptosis in cells expressing DNAJ-PKAc. Thus, our work indicates BAG2 as a marker for advanced FLC and a chemotherapeutic resistance factor in DNAJ-PKAc signaling scaffolds.

Use of Preoperative Endoscopic Capsule-Based pH Testing Before Bariatric Surgery.

BACKGROUND: Vertical sleeve gastrectomy is the most performed bariatric operation in the US; however, a significant number of patients suffer from persistent or new-onset reflux. No consensus for objective preoperative evaluation in these patients exists. We compared capsule-based pH testing vs GERD symptom scoring to determine extent of preoperative GERD to aid in procedure selection for bariatric surgery. STUDY DESIGN: An IRB-approved retrospective review of consecutive patients at a single institution was performed from April 2021 to December 2022. During initial consultation for bariatric surgery, a validated GERD symptom subjective survey was administered. All patients demonstrating interest in sleeve gastrectomy or had a history of reflux underwent upper endoscopy with capsule-based pH testing. RESULTS: Sixty-two patients underwent preoperative endoscopy with capsule-based pH testing and completed GERD symptom assessment survey(s). Median BMI was 43.4 kg/m 2 and 66.1% of patients were not taking a proton-pump inhibitor before performance of pH testing. There was negligible linear association between the objective DeMeester score obtained by capsule-based pH probe and GERD symptom survey scores. Median GERD symptom survey scores did not differ between patients with and without a diagnosis of GERD based on pH testing (all p values >0.11). CONCLUSIONS: An objective method for identifying severe GERD in the preoperative assessment may aid in the decision tree for procedure selection and informed consent process. Patients with significant preoperative GERD may be at higher risk for future GERD-related sleeve complications. Capsule-based pH testing may prove to be superior to subjective symptom scoring systems in this patient population.

Endovascular intervention for the treatment of epistaxis: cone beam CT review of anatomy, collateral, and treatment implications/efficacy.

Epistaxis is common, impacting more than half the population, and can require procedural intervention in approximately 10% of cases. With an aging population and increasing use of antiplatelets and anticoagulants, severe epistaxis is likely to increase in frequency significantly over the next two decades. Sphenopalatine artery embolization is rapidly becoming the most common type of procedural intervention. The efficacy of endovascular embolization is dependent on a refined understanding of the anatomy and collateral physiology of this circulation as well as the impact of temporizing measures such as nasal packing and inflation of a nasal balloon. Likewise, safety is dependent on a detailed appreciation of collateralization with the internal carotid artery and ophthalmic artery. Cone beam CT imaging has the resolution to enable a clear visualization of the anatomy and collateral circulation associated with the arterial supply to the nasal cavity, in addition to assisting with hemorrhage localization. We present a review of epistaxis treatment, a detailed description of anatomic and physiologic considerations informed by cone beam CT imaging, and a proposed protocol for sphenopalatine embolization for which there is currently no standard.

Stakeholder views on the design of National Health Service perinatal mental health services: 360-degree survey.

AIMS AND METHOD: At the start of a new community perinatal mental health service in Scotland we sought the opinions and aspirations of professional and lay stakeholders. A student elective project supported the creation of an anonymous 360-degree online survey of a variety of staff and people with lived experience of suffering from or managing perinatal mental health problems. The survey was designed and piloted with trainees and volunteer patients. RESULTS: A rich variety of opinions was gathered from the 60 responses, which came from a reasonably representative sample. Respondents provided specific answers to key questions and wrote free-text recommendations and concerns to inform service development. CLINICAL IMPLICATIONS: There is clear demand for the new expanded service, with strong support for provision of a mother and baby unit in the North of Scotland. The digital survey method could be adapted to generate future surveys to review satisfaction with service development and generate ideas for further change.