Surgical Outcomes and Sociodemographic Disparities Across All Races: An ACS-NSQIP and NHIS Multi-Institutional Analysis of Over 7.5 Million Patients.

Background: This study aims to fill the gap in large-scale, registry-based assessments by examining postoperative outcomes across diverse races/ethnicities. The focus is on identifying disparities and comparing them with socioeconomic demographics. Methods: In a registry-based cohort study using the 2008 to 2020 American College of Surgeons National Surgical Quality Improvement Program, we evaluated 24 postoperative outcomes through multivariable analysis, incorporating 28 preoperative risk factors. In a separate, independent analysis of the 2019 to 2020 National Health Interview Survey (NHIS) database, we examined sociodemographic racial/ethnic normative data. Results: Among 7,504,734 American College of Surgeons National Surgical Improvement Database patients specifying race, 83.8% were White (WT), 11.8% Black or African American (B/AA), 3.3% Asian (AS), 0.7% American Indian or Alaska Native (AI/AN), 0.4% Native Hawaiian or Pacific Islander (NH/PI), 7.3% Hispanic. Reoperation trends reveal favorable outcomes for WT, AS, and NH/PI patients compared with B/AA and AI/AN patients. AI/AN patients exhibit higher rates of wound healing issues, while AS patients experience lower rates. AS and B/AA patients are more prone to transfusions, with B/AA patients showing elevated rates of pulmonary embolism, deep vein thrombosis, renal failure, and insufficiency. Disparities in discharge destinations exist. Hispanic patients fare better than non-WT Hispanic patients, contingent on race. Racial groups (excluding Hispanic patients) with superior surgical outcomes from the NSQIP analysis were found in the NHIS analysis to report higher wealth, better healthcare access, improved food security, greater functional and societal independence, and lower frailty. Conclusions: Our study underscores racial disparities in surgical outcomes. Focused investigations into these complications could reveal underlying causes, informing healthcare policies to enhance surgical care universally.

Preventive Paradox? Postoperative Outcomes After Risk-Reducing Mastectomy and Direct-to-Implant Breast Reconstruction.

BACKGROUND: Risk-reducing mastectomy (RRM) with direct-to-implant (DTI) breast reconstruction is becoming increasingly important in breast cancer prevention. While the oncological benefits of RRM-DTI are well documented, there is a paucity of studies investigating its perioperative safety. METHODS: The ACS-NSQIP database (2008-2022) was queried to identify all patients who underwent RRM-DTI. Outcomes of interest included 30-day occurrence of reoperation, readmission, and surgical and medical complications. Multivariate logistic regression was used to determine factors associated with postoperative complications. RESULTS: A total of 1019 patients were included, with a mean age and BMI of 42.8 ± 10.9 years and 25.7 ± 5.8 kg/m², respectively. Complications occurred in 142 (14.0%) cases, with 103 (10.1%) reoperations and 51 (5.0%) readmissions. 62 (6.3%) surgical complications were recorded, the majority of which were superficial incisional infection (n = 19; 1.9%) and organ space infections (n = 19; 1.9%). Medical complications were rare (n = 13; 1.3%). Multivariable analyses revealed that higher BMI was significantly associated with any (OR:1.06, P < .0001), surgical (OR:1.08, P < .0001), and medical complications (OR:1.08, P = .04). Patients with bleeding disorders were at a significantly higher risk of any complications (OR:5.5, P = .03), while outpatient setting (OR:1.9, P = .03) and corticosteroid use (OR:6.6, P = .01) were identified as independent predictors of surgical complications. CONCLUSION: The risk of adverse events following RRM-DTI should not be underestimated, with a 30-day complication rate of 14%. Higher BMI, bleeding disorders, outpatient setting, and corticosteroid use were identified as risk factors. These findings underscore the need for thorough preoperative risk stratification, patient counseling, and health optimization to optimize surgical outcomes.

Frailty as a sequela of burn injury: a post hoc analysis of the "RE-ENERGIZE" multicenter randomized-controlled trial and the National Health Interview Survey.

BACKGROUND: With advancements in burn treatment and intensive care leading to decreased mortality rates, a growing cohort of burn survivors is emerging. These individuals may be susceptible to frailty, characterized by reduced physiological reserve and increased vulnerability to stressors commonly associated with aging, which significantly complicates their recovery process. To date, no study has investigated burns as a potential risk factor for frailty. This study aimed to determine the short-term prevalence of frailty among burn survivors' months after injury and compare it with that of the general population. METHODS: A post hoc analysis was conducted on the Randomized Trial of Enteral Glutamine to Minimize the Effects of Burn Injury (RE-ENERGIZE) trial, an international randomized-controlled trial involving 1200 burn injury patients with partial- or full-thickness burns. Participants who did not complete the 36-Item Short Form Health Survey (SF-36) questionnaire were excluded. Data for the general population were obtained from the 2022 National Health Interview Survey (NHIS). Frailty was assessed using the FRAIL (Fatigue, Resistance, Ambulation, Illness, Loss of weight) scale. Due to lack of data on loss of weight, for the purposes of this study, malnutrition was used as the fifth variable. Illness and malnutrition were based on admission data, while fatigue, resistance, and ambulation were determined from post-discharge responses to the SF-36. The burn cohort and general population groups were matched using propensity score matching and compared in terms of frailty status. Within the burn group, patients were divided into different subgroups based on their frailty status, and the differences in their (instrumental) activities of daily living (iADL and ADL) were compared. A multivariable analysis was performed within the burn cohort to identify factors predisposing to frailty as well as compromised iADL and ADL. RESULTS: Out of the 1200 burn patients involved in the study, 600 completed the required questionnaires [follow-up time: (5.5 ± 2.3) months] and were matched to 1200 adults from the general population in the U.S. In comparison to the general population, burn patients exhibited a significantly higher likelihood of being pre-frail (42.3% vs. 19.8%, P < 0.0001), or frail (13.0% vs. 1.0%, P < 0.0001). When focusing on specific components, burn patients were more prone to experiencing fatigue (25.8% vs. 13.5%, P < 0.0001), limited resistance (34.0% vs. 2.7%, P < 0.0001), and restricted ambulation (41.8% vs. 3.8%, P < 0.0001). Conversely, the incidence rate of illness was observed to be higher in the general population (1.2% vs. 2.8%, P = 0.03), while no significant difference was detected regarding malnutrition (2.3% vs. 2.6%, P = 0.75). Furthermore, in comparison with robust burn patients, it was significantly more likely for pre-frail and frail patients to disclose compromise in ADL and iADL. The frail cohort reported the most pronounced limitation. CONCLUSIONS: Our findings suggest a higher incidence of post-discharge frailty among burn survivors in the short-term following injury. Burn survivors experience compromised fatigue, resistance, and ambulation, while rates of illness and malnutrition were lower or unchanged, respectively. These results underscore the critical need for early identification of frailty after a burn injury, with timely and comprehensive involvement of a multidisciplinary team including burn and pain specialists, community physicians, physiotherapists, nutritionists, and social workers. This collaborative effort can ensure holistic care to address and mitigate frailty in this patient population.

Loss of Functional Independence after Plastic Surgery in Older Patients: American College of Surgeons National Surgical Quality Improvement Program Database.

Background: Maintenance of functional independence is an important patient-centered outcome. As the evidence on loss of independence (LOI) in older patients undergoing plastic surgery is lacking, this study investigates the extent of LOI, identifying factors associated with LOI. Methods: The 2021-2022 American College of Surgeons National Surgical Quality Improvement Program database was searched to identify patients (>65 years old) who underwent plastic surgery and provided data on their functional independence. The primary outcome was LOI on discharge. Data on perioperative factors, including patient characteristics and comorbidities, surgical details, and outcome measures such as operation time, length of hospital stay, surgical and medical complications, mortality, and discharge destination were extracted. Results: Of 2112 patients who underwent plastic surgery, most were independent on discharge (n = 1838, 87%). A total of 163 patients lost their independence (LOI rate: 7.7%). Patients discharged as dependent were more likely to have experienced surgical and medical complications, and less likely to be discharged home (all <0.0001). Factors independently associated with LOI included age (1.08, P = 0.0001), a history of a fall within the last 6 months (2.01, P = 0.03), inpatient setting (2.30, P = 0.0002), operation time (1.00, P = 0.01), and length of hospital stay (1.13, P = 0.0001). Conclusions: Approximately 8% of older patients undergoing plastic surgery are found to be at risk of postsurgical LOI. Future prospective and multicenter studies should evaluate the risks for short- and long-term LOI with the goal of developing interventions that optimize the care for this patient population.

A multicentre clinical trial evaluating the outcomes of two application regimens of a unique keratin-based graft in the treatment of Wagner grade one non-healing diabetic foot ulcers.

Diabetic foot complications that lead to lower extremity amputations pose a significant challenge to the entire global health system. In this multicentre clinical trial, 26 patients with chronic Wagner one diabetic foot ulcers (DFUs) were treated with a unique human keratin matrix graft applied either weekly or bi-weekly, in addition to standard of care. The hypothesis was that bi-weekly application would be similar to weekly application. The primary endpoint was complete wound closure by 12 weeks, and secondary endpoints included healing time, percent area reduction and weekly changes in peripheral neuropathy, pain and quality of life. In the intent-to-treat population, 77% (10/13) of DFUs treated with bi-weekly application healed compared with 69% (9/13) treated with weekly application. The mean time to heal within 12 weeks in the bi-weekly group was 61 days and in the weekly group was 54 days. The mean percent area reduction at 12 weeks was 94.7% in the bi-weekly group compared with 84.8% in the weekly group. The number of grafts used in the bi-weekly group was 3.9 compared with 6.2 in the weekly group. The results of this trial confirm our hypothesis that whether bi-weekly or weekly application of the unique keratin matrix graft is used to treat nonhealing indolent DFUs, there is a high rate of complete healing. Based on these results, future studies should be conducted that further investigate the use of this novel human keratin matrix graft for the treatment of chronic DFUs.

A qualitative investigation into the effectiveness of a housing navigator program linking justice-involved clients with recovery housing.

BACKGROUND: Roughly 24-36% of people who are incarcerated in the U.S. are formally diagnosed with opioid use disorder (OUD). Once released, individuals involved with the criminal legal system (CLS) face increased risks of return to use and fatality and are 129 times more likely to die from an overdose within the first two weeks of release compared to those without CLS involvement. People who are CLS-involved and who are seeking a recovery living environment can access temporary stable housing through recovery homes. However, entering a recovery home can be difficult due to fragmentation among recovery housing organizations and their non-uniform application and screening procedures. A navigation pilot program was implemented to provide clients with recovery home placement advice, pre-screening, and referrals in Cook County, IL. Existing research on recovery homes has rarely examined the importance of recovery housing navigation for enhancing service engagement among CLS-involved individuals receiving medications for OUD. METHODS: Semi-structured qualitative interviews were conducted with 22 clients and three recovery housing navigators as part of a program evaluation of the navigation program pilot. Qualitative software was used to organize and qualitatively analyze transcripts through several rounds of coding producing emergent themes, which were then triangulated, and expanded using navigator data. RESULTS: Clients seeking recovery home services reported multiple prior challenges securing safe and supportive recovery living environments. Despite low initial expectations, clients described their interactions with housing navigators in favorable terms and felt navigators worked with them effectively to identify and meet their housing and substance use needs in a timely manner. Clients also commented on their partnerships with the navigator throughout the process. Interactions with navigators also calmed fears of rejection many clients had previously experienced and still harbored about the process, which bolstered client-navigator relationships and client motivation to engage with additional services. CONCLUSION: Evidence from this study suggests recovery home navigation can improve the speed and efficiency with which clients are connected to appropriate services that are tailored to their specific needs as well as increase client motivation to engage with a myriad of recovery services.

"A lot of moving parts": Recovery home challenges linking and housing individuals with criminal legal system involvement.

INTRODUCTION: There are high rates of substance use disorder (SUD) among people released from carceral settings and, upon release, many of these people also face unstable housing situations, posing challenges to connecting with resources to facilitate SUD recovery. Recovery homes provide a temporary sober living environment for those seeking both SUD recovery and transition back to the community after carceral release. However, successful recovery home placement for this population can prove difficult, and there is a need for research to identify ways to overcome them. METHODS: The current qualitative study seeks to understand barriers to recovery home access for people leaving carceral settings and identify potential best practices for overcoming these barriers from the perspective of recovery home directors. The study conducted semi-structured interviews at two data collection points with eight recovery home directors from sites participating in a housing linkage and placement intervention pilot. The research team used qualitative software to identify and organize directors' experiences and practices in housing and supporting this population. RESULTS: Recovery home directors identified significant barriers to linkage from carceral settings, including difficulties communicating and coordinating placement with potential residents while still incarcerated. Interviews also revealed approaches recovery home directors take to improve recovery home placement, such as sharing information and resources with carceral settings prior to release and helping residents avoid reincarceration by managing relationships with court agents and parole. CONCLUSION: Recovery resident directors have considerable insight into the most significant placement challenges faced by recovery homes upon carceral release as well as experience with potential solutions for overcoming them. Directors can be the key to direct seamless support and continuity of care for criminal legal system involved individuals through coordination with jails, prisons, and other community resources. Directors can also play a significant role in the successful completion of probation and parole by helping residents avoid further issues with the legal system. These directors view working cooperatively with residents as an effective approach to ensuring clients adhere to court orders and are successful in recovery and reentry.

Novel N,N-Dimethyl-idarubicin Analogues Are Effective Cytotoxic Agents for ABCB1-Overexpressing, Doxorubicin-Resistant Cells.

Anthracyclines comprise one of the most effective anticancer drug classes. Doxorubicin, daunorubicin, epirubicin, and idarubicin have been in clinical use for decades, but their application remains complicated by treatment-related toxicities and drug resistance. We previously demonstrated that the combination of DNA damage and histone eviction exerted by doxorubicin drives its associated adverse effects. However, whether the same properties dictate drug resistance is unclear. In the present study, we evaluate a library of 40 anthracyclines on their cytotoxicity, intracellular uptake, and subcellular localization in K562 wildtype versus ABCB1-transporter-overexpressing, doxorubicin-resistant cells. We identify several highly potent cytotoxic anthracyclines. Among these, N,N-dimethyl-idarubicin and anthracycline (composed of the idarubicin aglycon and the aclarubicin trisaccharide) stand out, due to their histone eviction-mediated cytotoxicity toward doxorubicin-resistant cells. Our findings thus uncover understudied anthracycline variants warranting further investigation in the quest for safer and more effective anticancer agents that circumvent cellular export by ABCB1.

A novel surgical risk predictor combining frailty and hypoalbuminemia - A cohort study of 9.8m patients from the ACS-NSQIP database.

INTRODUCTION: The functional decline seen in frail patients is associated with significant morbidity and mortality. The modified frailty index 5 (mFI-5) score is an accepted risk predictor score in surgery. Hypoalbuminemia has been correlated with poor postoperative outcomes.There exists, however, a gap in the literature regarding the combined assessment of frailty and hypoalbuminemia and the predictive power of this combined assessment. This retrospective cohort study aimed to investigate the association of preoperative albumin and frailty, as assessed with the mFI-5 score, and its ability to predict surgical outcomes. METHODS: We queried the ACS-NSQIP database (2008-2021) to identify all surgical patients. Perioperative data, including demographics and preoperative laboratory values, including albumin, were collected. The predictive power of the mFI-5 and hypoalbuminemia (Alb) independently, and in combination (mFI-5+Alb), was assessed using multivariable linear and logistic regression models 30-day outcomes were assessed including mortality, length of hospital stay, reoperation, medical and surgical complications, and discharge destination. RESULTS: A total of 9,782,973 patients were identified of whom 4,927,520 (50.4%) were non-frail (mFI=0), 3,266,636 had a frailty score of 1 (33.4%), 1,373,968 a score of 2 (14.0%), 188,821 a score of 3 (1.9%) and 26,006 a score greater or equal to 4 (0.3%). Albumin levels were available for 4,570,473 patients (46.7%), of whom 848,315 (18.6%) had hypoalbuminemia. The combined assessment (mFI-5+Alb) was found to be a more accurate risk predictor than each factor independently for all outcomes. A weak negative correlation between serum albumin levels and mFI scores was established (Spearman R: -0.2; <0.0001). CONCLUSIONS: Combined assessment of frailty and albumin was the strongest risk predictor. Therefore, for patients undergoing surgery, we recommend consideration of both serum albumin and frailty in order to optimally determine perioperative planning, including multi-disciplinary care mobilization and pre- and posthabilitation.

Linkage facilitation for opioid use disorder in criminal legal system contexts: a primer for researchers, clinicians, and legal practitioners.

At the intersection of drug policy, the opioid crisis, and fragmented care systems, persons with opioid use disorder (OUD) in the United States are significantly vulnerable to contact with the criminal legal system (CLS). In CLS settings, provision of evidence-based treatment for OUD is variable and often secondary to punitive approaches. Linkage facilitation at every touch point along the CLS Sequential Intercept Model has potential to redirect persons with OUD into recovery-oriented systems of care, increase evidence-based OUD treatment connections, and therefore reduce CLS re-exposure risk. Research in this area is still nascent. Thus, this narrative review explores the state of the science on linkage facilitation across the varied CLS contexts, including general barriers, facilitators, and opportunities for using linkage facilitation for OUD treatment and related services. Following the CLS Sequential Intercept Model, the specific CLS contexts examined include community services, police encounters, the courts (pre- and post-disposition), incarceration (pre-trial detention, jail, and prison), reentry (from jails, prisons, and unified systems), and community supervision (probation and parole). Examples of innovative linkage facilitation interventions are drawn from the Justice Community Opioid Innovation Network (JCOIN). Areas for future research and policy change are highlighted to advance the science of linkage facilitation for OUD services in the CLS.

Expanding the empirical study of virtual reality beyond empathy to compassion, moral reasoning, and moral foundations.

This study utilizes a controlled experimental design to investigate the influence of a virtual reality experience on empathy, compassion, moral reasoning, and moral foundations. With continued debate and mixed results from previous studies attempting to show relationships between virtual reality and empathy, this study takes advantage of the technology for its ability to provide a consistent, repeatable experience, broadening the scope of analysis beyond empathy. A systematic literature review identified the most widely used and validated moral psychology assessments for the constructs, and these assessments were administered before and after the virtual reality experience. The study is comprised of two pre-post experiments with student participants from a university in the United States. The first experiment investigated change in empathy and moral foundations among 44 participants, and the second investigated change in compassion and moral reasoning among 69 participants. The results showed no significant change in empathy nor compassion, but significant change in moral reasoning from personal interest to post-conventional stages, and significant increase in the Care/harm factor of moral foundations. By testing four of the primary constructs of moral psychology with the most widely used and validated assessments in controlled experiments, this study attempts to advance our understanding of virtual reality and its potential to influence human morality. It also raises questions about our self-reported assessment tools and provides possible new insights for the constructs examined.

A nomogram for predicting outcomes following pedicled flap reconstruction of the lower extremity.

INTRODUCTION: Lower extremity reconstructions with soft tissue flaps account for a significant proportion of reconstructive surgery. Pedicled flaps are a procedure of choice, particularly in multimorbid patients and those with small to medium-sized defects. Complication rates are high and should not be underestimated, with accurate preoperative risk factor assessment being imperative. METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program Database (2008-2021), we analyzed all patients who underwent pedicled flap reconstruction of the lower extremity. Demographic data, comorbidities, and perioperative data were extracted. We identified risk factors of major surgical complications within 30 days of surgery through uni- and multivariate regression analyses. On this basis, a nomogram for predicting the risk of complications was developed to allow for feasible point-of-care risk assessment. RESULTS: A total of 6475 adult patients were identified. The most common comorbidities were hypertension (n = 3363, 51.9%) and obesity (n = 2306, 35.6%) and most common American Society of Anesthesiologists (ASA) class was class 3 (n = 3703, 57.2%). The most common complication was bleeding/transfusion (n = 1293, 19.9%). Multivariate regression revealed longer procedures, inpatient setting, higher ASA scores, hypertension, and procedures performed by orthopedic and vascular surgeons as predictors for higher risk of post-operative complications. CONCLUSION: Leveraging a risk- and case-mix-adjusted multi-institutional database, a nomogram for post-operative surgical complications within 30 days after pedicled flap reconstruction in the lower extremity was developed. This broadly applicable risk prediction tool can aid in decision-making when assessing patient eligibility.

Patient experiences of buprenorphine dispensing from a mobile medical unit.

BACKGROUND: Overdose deaths continue to rise within the United States, despite effective treatments such as buprenorphine and methadone for opioid use disorder (OUD). Mobile medical units with the ability to dispense buprenorphine have been developed to engage patients and eliminate barriers to accessing OUD treatment. This study reports survey responses of patients of a mobile medical unit dispensing buprenorphine in areas of Chicago, IL with high overdose rates. METHODS: All patients who were dispensed buprenorphine via the mobile medical unit were invited to participate in a 7-item anonymous survey between May 24, 2023, and August 25, 2023. The survey included 5-point satisfaction scale, multiple-choice, and open-ended questions. Outcomes included satisfaction with buprenorphine dispensing from the mobile medical unit, satisfaction with filling buprenorphine at a pharmacy in the past, barriers experienced at pharmacies when filling buprenorphine, and whether the client would have started treatment that day if the mobile medical unit had not been present. Satisfaction scale and multiple-choice question responses were assessed using descriptive statistics. Wilcoxon signed-rank test was used to compare median satisfaction levels between receiving buprenorphine from the mobile medical unit versus filling a buprenorphine prescription at a community pharmacy. Open-ended questions were analyzed qualitatively using inductive thematic analysis. RESULTS: 106 unique patients were dispensed buprenorphine from the mobile unit during the study period. Of these patients, 54 (51%) completed the survey. Respondents reported high satisfaction with the buprenorphine dispensing process as a part of a mobile medical unit. Of those who had previously filled buprenorphine at a pharmacy, 83% reported at least one barrier, with delays in prescription dispensing from a community pharmacy, lack of transportation to/from the pharmacy, and opioid withdrawal symptoms being the most common barriers. 87% reported they would not have started buprenorphine that same day if the mobile medical unit had not been present. Nearly half of survey participants reported having taken buprenorphine that was not prescribed to them. Qualitative analysis of open-ended survey responses noted the importance of convenient accessibility, comprehensive care, and a non-judgmental environment. CONCLUSIONS: Mobile medical units that dispense buprenorphine are an innovative model to reach patients with OUD who have significant treatment access barriers. This study found that patients who experienced barriers to accessing buprenorphine from a pharmacy were highly satisfied with the mobile medical unit's buprenorphine dispensing process. Programs seeking to develop mobile buprenorphine dispensing programs should consider patient priorities of accessibility, comprehensive care, and welcoming, non-judgmental environments.

Sustained generation of neurons destined for neocortex with oxidative metabolic upregulation upon filamin abrogation.

Neurons in the neocortex are generated during embryonic development. While the adult ventricular-subventricular zone (V-SVZ) contains cells with neural stem/progenitors' characteristics, it remains unclear whether it has the capacity of producing neocortical neurons. Here, we show that generating neurons with transcriptomic resemblance to upper layer neocortical neurons continues in the V-SVZ of mouse models of a human condition known as periventricular heterotopia by abrogating Flna and Flnb. We found such surplus neurogenesis was associated with V-SVZ's upregulation of oxidative phosphorylation, mitochondrial biogenesis, and vascular abundance. Additionally, spatial transcriptomics analyses showed V-SVZ's neurogenic activation was coupled with transcriptional enrichment of genes in diverse pathways for energy metabolism, angiogenesis, cell signaling, synaptic transmission, and turnovers of nucleic acids and proteins in upper cortical layers. These findings support the potential of generating neocortical neurons in adulthood through boosting brain-wide vascular circulation, aerobic adenosine triphosphate synthesis, metabolic turnover, and neuronal activity.

Fixed-target pump-probe SFX: eliminating the scourge of light contamination.

X-ray free-electron laser (XFEL) light sources have enabled the rapid growth of time-resolved structural experiments, which provide crucial information on the function of macromolecules and their mechanisms. Here, the aim was to commission the SwissMX fixed-target sample-delivery system at the SwissFEL Cristallina experimental station using the PSI-developed micro-structured polymer (MISP) chip for pump-probe time-resolved experiments. To characterize the system, crystals of the light-sensitive protein light-oxygen-voltage domain 1 (LOV1) from Chlamydomonas reinhardtii were used. Using different experimental settings, the accidental illumination, referred to as light contamination, of crystals mounted in wells adjacent to those illuminated by the pump laser was examined. It was crucial to control the light scattering from and through the solid supports otherwise significant contamination occurred. However, the results here show that the opaque MISP chips are suitable for defined pump-probe studies of a light-sensitive protein. The experiment also probed the sub-millisecond structural dynamics of LOV1 and indicated that at Δt = 10 µs a covalent thioether bond is established between reactive Cys57 and its flavin mononucleotide cofactor. This experiment validates the crystals to be suitable for in-depth follow-up studies of this still poorly understood signal-transduction mechanism. Importantly, the fixed-target delivery system also permitted a tenfold reduction in protein sample consumption compared with the more common high-viscosity extrusion-based delivery system. This development creates the prospect of an increase in XFEL project throughput for the field.

Integration of a Community Opioid Treatment Program into a Federally Qualified Health Center.

OBJECTIVES: With the increasing rates of opioid overdose deaths in the United States, barriers to treatment access for patients seeking medications for opioid use disorder (OUD), and challenges of initiating buprenorphine in patients who use fentanyl, it is essential to explore novel approaches to expanding access to methadone treatment. An opioid treatment program (OTP) and a federally qualified health center (FQHC) partnered to develop and implement an innovative integrated methadone and primary care treatment model. The process for integrating an OTP and FQHC to provide methadone treatment in the primary care setting will be discussed. METHODS: An OTP methadone dispensing site was co-located in the FQHC, utilizing a staffing matrix built on the expertise of each stakeholder. The OTP managed DEA and state regulatory processes, whereas the FQHC physicians provided medical treatment, including methadone treatment protocols, treatment plans, and primary care. Patient demographics, medical history, and retention data for those who entered the program between January 2021 and February 2023 were collected through chart review and analyzed with descriptive statistics. RESULTS: A total of 288 OTP-FHQC patients were enrolled during the study. Retention rates in methadone treatment at 90 and 180 days were similar to partner clinics. CONCLUSIONS: Collaboration between FQHCs and OTPs is operationally feasible and can be achieved utilizing the current staffing model of the FQHC and OTP. This model can increase access to treatment for OUD and primary care for an urban, underserved patient population.

Dietary Phosphorus Levels Influence Protein-Derived Uremic Toxin Production in Nephrectomized Male Rats.

Gut microbiota-derived uremic toxins (UT) accumulate in patients with chronic kidney disease (CKD). Dietary phosphorus and protein restriction are common in CKD treatment, but the relationship between dietary phosphorus, a key nutrient for the gut microbiota, and protein-derived UT is poorly studied. Thus, we explored the relationship between dietary phosphorus and serum UT in CKD rats. For this exploratory study, we used serum samples from a larger study on the effects of dietary phosphorus on intestinal phosphorus absorption in nephrectomized (Nx, n = 22) or sham-operated (sham, n = 18) male Sprague Dawley rats. Rats were randomized to diet treatment groups of low or high phosphorus (0.1% or 1.2% w/w, respectively) for 1 week, with serum trimethylamine oxide (TMAO), indoxyl sulfate (IS), and p-cresol sulfate (pCS) analyzed by LC-MS. Nx rats had significantly higher levels of serum TMAO, IS, and pCS compared to sham rats (all p < 0.0001). IS showed a significant interaction between diet and CKD status, where serum IS was higher with the high-phosphorus diet in both Nx and sham rats, but to a greater extent in the Nx rats. Serum TMAO (p = 0.24) and pCS (p = 0.34) were not affected by dietary phosphorus levels. High dietary phosphorus intake for 1 week results in higher serum IS in both Nx and sham rats. The results of this exploratory study indicate that reducing dietary phosphorus intake in CKD may have beneficial effects on UT accumulation.

Associations among drug acquisition and use behaviors, psychosocial attributes, and opioid-involved overdoses.

AIMS: This study sought to develop and assess an exploratory model of how demographic and psychosocial attributes, and drug use or acquisition behaviors interact to affect opioid-involved overdoses. DESIGN: We conducted exploratory and confirmatory factor analysis (EFA/CFA) to identify a factor structure for ten drug acquisition and use behaviors. We then evaluated alternative structural equation models incorporating the identified factors, adding demographic and psychosocial attributes as predictors of past-year opioid overdose. SETTING AND PARTICIPANTS: We used interview data collected for two studies recruiting opioid-misusing participants receiving services from a community-based syringe services program. The first investigated current attitudes toward drug-checking (N = 150). The second was an RCT assessing a telehealth versus in-person medical appointment for opioid use disorder treatment referral (N = 270). MEASUREMENTS: Demographics included gender, age, race/ethnicity, education, and socioeconomic status. Psychosocial measures were homelessness, psychological distress, and trauma. Self-reported drug-related risk behaviors included using alone, having a new supplier, using opioids with benzodiazepines/alcohol, and preferring fentanyl. Past-year opioid-involved overdoses were dichotomized into experiencing none or any. FINDINGS: The EFA/CFA revealed a two-factor structure with one factor reflecting drug acquisition and the second drug use behaviors. The selected model (CFI = .984, TLI = .981, RMSEA = .024) accounted for 13.1% of overdose probability variance. A latent variable representing psychosocial attributes was indirectly associated with an increase in past-year overdose probability (ß = .234, p = .001), as mediated by the EFA/CFA identified latent variables: drug acquisition (ß = .683, p < .001) and drug use (ß = .567, p = .001). Drug use behaviors (ß = .287, p = .04) but not drug acquisition (ß = .105, p = .461) also had a significant, positive direct effect on past-year overdose. No demographic attributes were significant direct or indirect overdose predictors. CONCLUSIONS: Psychosocial attributes, particularly homelessness, increase the probability of an overdose through associations with risky drug acquisition and drug-using behaviors. Further research is needed to replicate these findings with populations at high-risk of an opioid-related overdose to assess generalizability and refine the metrics used to assess psychosocial characteristics.

Standardized Protocols for Clinical and Histopathological Characterization of Hidradenitis Suppurativa Tissue Specimens.

Methods for describing and reporting the clinical and histologic characteristics of cutaneous tissue samples from patients with hidradenitis suppurativa (HS) are not currently standardized, limiting clinicians' and scientists' ability to uniformly record, report, and communicate about the characteristics of tissue used in translational experiments. A recently published consensus statement outlined morphological definitions of typical HS lesions, but no consensus has been reached regarding clinical characterization and examination of HS tissue samples. In this study, we aimed to establish a protocol for reporting histopathologic and clinical characteristics of HS tissue specimens. This study was conducted from May 2023 to August 2023. Experts in clinical care, dermatopathology, and translational research were recruited, and a modified Delphi technique was used to develop a protocol for histologic reporting and clinical characterization of submitted tissue specimens from patients with HS. A total of 27 experts participated (14 dermatologists, 3 fellowship-trained dermatopathologists, 3 plastic surgeons, 3 general surgeons, and 4 research scientists) in creating and reviewing protocols for the clinical and histopathological examination of HS tissue specimens. The protocols were formatted as a synoptic report and will help to consistently classify specimens in biobanks on the basis of histologic features and more accurately report and select samples used in translational research projects.

Transcriptional synergy in human aortic endothelial cells is vulnerable to combination p300/CBP and BET bromodomain inhibition.

Combinatorial signaling by proinflammatory cytokines synergizes to exacerbate toxicity to cells and tissue injury during acute infections. To explore synergism at the gene-regulatory level, we investigated the dynamics of transcription and chromatin signaling in response to dual cytokines by integrating nascent RNA imaging mass spectrometry, RNA sequencing, amplification-independent mRNA quantification, assay for transposase-accessible chromatin using sequencing (ATAC-seq), and transcription factor profiling. Costimulation with interferon-gamma (IFNγ) and tumor necrosis factor alpha (TNFα) synergistically induced a small subset of genes, including the chemokines CXCL9, -10, and -11. Gene induction coincided with increased chromatin accessibility at non-coding regions enriched for p65 and STAT1 binding sites. To discover coactivator dependencies, we conducted a targeted chemogenomic screen of transcriptional inhibitors followed by modeling of inhibitor dose-response curves. These results identified high efficacy of either p300/CREB-binding protein (CBP) or bromodomain and extra-terminal (BET) bromodomain inhibitors to disrupt induction of synergy genes. Combination p300/CBP and BET bromodomain inhibition at half-maximal inhibitory concentrations (subIC50) synergistically abrogated IFNγ/TNFα-induced chemokine gene and protein levels.