Clinical Characteristics, Treatment Patterns, and Outcomes of Patients With Locally Advanced/Metastatic Hepatocellular Carcinoma Treated at the Veterans Health Administration.

PURPOSE: This study retrospectively reviewed the outcomes of patients with advanced hepatocellular carcinoma (HCC) receiving atezolizumab with bevacizumab (A + B) therapy at the Veterans Health Administration (VHA). PATIENTS AND METHODS: Patients with advanced HCC who received first-line systemic therapy with A + B at the VHA between December 1, 2019, and March 1, 2022, were selected from electronic medical records (EMR) using ICD-9 and ICD-10 codes. Abstractors reviewed the EMR of the patients from their index date of A + B initiation until death or their last VHA visit, with the study period ending on January 31, 2023. The chi-square test was used to compare rates, and the Mann-Whitney test was used to compare medians. RESULTS: A total of 332 patients met the study criteria. The median age was 67 years; 99% were male, 63% were non-Hispanic Whites, 26% were Black, and 66% had an Eastern Cooperative Oncology Group performance status of ≥1. 84% had child Pugh score (CPS) class A, 16% had CPS classes B and C, 62% had a grade 2 albumin-bilirubin score, 56% had HCC caused by viral hepatitis, 80% had cirrhosis, and 67% had received prior local therapies. The 6-month progression-free survival (PFS) was 59%, while the 1-year PFS rate was 36%. Overall survival (OS) at 1-year was 52% in our study. CONCLUSION: In real world, despite having similar PFS as the phase III IMbrave 150 trial, our OS at 12 months was lower (52% vs. 67%) because our study included a higher proportion of elderly patients with moderate liver dysfunction and a 40% non-White. This study provided real-world outcomes that differed from the study population in a pivotal trial.

Care Fragmentation, Social Determinants of Health, and Postoperative Mortality in Older Veterans.

INTRODUCTION: Veterans Affairs Surgical Quality Improvement Program (VASQIP) benchmarking algorithms helped the Veterans Health Administration (VHA) reduce postoperative mortality. Despite calls to consider social risk factors, these algorithms do not adjust for social determinants of health (SDoH) or account for services fragmented between the VHA and the private sector. This investigation examines how the addition of SDoH change model performance and quantifies associations between SDoH and 30-d postoperative mortality. METHODS: VASQIP (2013-2019) cohort study in patients ≥65 y old with 2-30-d inpatient stays. VASQIP was linked to other VHA and Medicare/Medicaid data. 30-d postoperative mortality was examined using multivariable logistic regression models, adjusting first for clinical variables, then adding SDoH. RESULTS: In adjusted analyses of 93,644 inpatient cases (97.7% male, 79.7% non-Hispanic White), higher proportions of non-veterans affairs care (adjusted odds ratio [aOR] = 1.02, 95% CI = 1.01-1.04) and living in highly deprived areas (aOR = 1.15, 95% CI = 1.02-1.29) were associated with increased postoperative mortality. Black race (aOR = 0.77, CI = 0.68-0.88) and rurality (aOR = 0.87, CI = 0.79-0.96) were associated with lower postoperative mortality. Adding SDoH to models with only clinical variables did not improve discrimination (c = 0.836 versus c = 0.835). CONCLUSIONS: Postoperative mortality is worse among Veterans receiving more health care outside the VA and living in highly deprived neighborhoods. However, adjusting for SDoH is unlikely to improve existing mortality-benchmarking models. Reduction efforts for postoperative mortality could focus on alleviating care fragmentation and designing care pathways that consider area deprivation. The adjusted survival advantage for rural and Black Veterans may be of interest to private sector hospitals as they attempt to alleviate enduring health-care disparities.

Current use, training, and barriers in point-of-care ultrasound in nephrology: A national survey of VA medical centers.

BACKGROUND: Point-of-care ultrasound (POCUS) can improve diagnostic accuracy, reduce procedural complications and enhance physician-patient interactions in nephrology. Currently, there is limited knowledge about how practicing nephrologists are using POCUS. OBJECTIVE: This study aimed to characterize current POCUS use, training needs, and barriers to use among nephrology groups. MATERIALS AND METHODS: A prospective observational study of all Veterans Affairs (VA) medical centers was conducted between August 2019 and March 2020 using a web-based survey sent to all chiefs of staff and nephrology specialty chiefs. RESULTS: Chiefs of staff (n = 130) and nephrology chiefs (n = 79) completed surveys on facility- and service-level POCUS use (response rates of 100% and 77%, respectively). Current diagnostic or procedural POCUS use was reported by 41% of nephrology groups, and the most common POCUS applications were central line insertion (28%) and assessment of urinary retention (23%), hydronephrosis (18%), volume status (15%), and bladder (14%). Lack of training was the most common barrier (72%), and most nephrology groups (65%) desired POCUS training. Limited access to ultrasound equipment and POCUS training were barriers reported by 54% and 18% of groups, respectively. CONCLUSION: A minority of nephrology groups currently use common POCUS applications including evaluation of urinary retention, hydronephrosis, and volume status. The most common barriers to POCUS use in nephrology were lack of trained providers and ultrasound equipment. Investment in POCUS training and infrastructure is needed to expand and standardize POCUS use in nephrology.

The effect of level of injury on diabetes incidence and mortality after spinal cord injury - a longitudinal cohort study.

STUDY DESIGN: Retrospective longitudinal cohort study of veterans with SCI. OBJECTIVES: Spinal cord injury (SCI) is associated with an increased risk of developing diabetes mellitus (DM), likely due to body composition alterations and autonomic nervous system dysfunction. These factors are more pronounced in persons with tetraplegia (TP) versus paraplegia (PP). However, the effect of level of injury (LOI) on DM incidence is largely unknown. Therefore, the objective is to examine the effect of LOI on DM incidence in persons with SCI. SETTING: South Texas Veterans Health Care System. METHODS: We obtained electronic record data on age, sex, race/ethnicity, LOI and HbA1c concentration from January 1st 2001 through December 31st 2021. Cox proportional hazard regression analyses were used to assess the association between LOI, DM and all-cause mortality. RESULTS: Among 728 non-diabetic veterans with SCI (350 TP/ 378 PP, 52 ± 15 years, 690 male/38 female) 243 developed DM, of which 116 with TP and 127 with PP. Despite chronological variations between TP and PP, DM risk over the entire follow-up did not differ between the groups (hazard ratio (HR): 1.06, 95% CI: 0.82-1.38). Mortality was higher in TP versus PP (HR: 1.40, 95% CI: 1.09-1.78). However, developing DM did not increase the risk of death, regardless of LOI (HR: 1.07, 95% CI: 0.83-1.37). CONCLUSION: Despite chronological variations between both groups, the level of injury had minimal effect on long-term DM development in this cohort of veterans with SCI. Sponsorship NIH (DK105379; MS), RR&D SPiRE (I21RX003724-01A1; MT and SH).

Interdisciplinary Team Meetings in Practice: an Observational Study of IDTs, Sensemaking Around Care Transitions, and Readmission Rates.

BACKGROUND: Interdisciplinary teams (IDTs) have been implemented to improve collaboration in hospital care, but their impact on patient outcomes, including readmissions, has been mixed. These mixed results might be rooted in differences in organization of IDT meetings between hospitals, as well as variation in IDT characteristics and function. We hypothesize that relationships between IDT members are an important team characteristic, influencing IDT function in terms of how members make sense of what is happening with patients, a process called sensemaking OBJECTIVE: (1) To describe how IDT meetings are organized in practice, (2) assess differences in IDT member relationships and sensemaking during patient discussions, and (3) explore their potential association with risk-stratified readmission rates (RSRRs). DESIGN: Observational, explanatory convergent mixed-methods case-comparison study of IDT meetings in 10 Veterans Affairs hospitals. PARTICIPANTS: Clinicians participating in IDTs and facility leadership. APPROACH: Three-person teams observed and recorded IDT meetings during week-long visits. We used observational data to characterize relationships and sensemaking during IDT patient discussions. To assess sensemaking, we used 2 frameworks that reflected sensemaking around each patient's situation generally, and around care transitions specifically. We examined the association between IDT relationships and sensemaking, and RSRRs. KEY RESULTS: We observed variability in IDT organization, characteristics, and function across 10 hospitals. This variability was greater between hospitals than between teams at the same hospital. Relationship characteristics and both types of sensemaking were all significantly, positively correlated. General sensemaking regarding each patient was significantly negatively associated with RSRR (- 0.65, p = 0.044). CONCLUSIONS: IDTs vary not only in how they are organized, but also in team relationships and sensemaking. Though our design does not allow for inferences of causation, these differences may be associated with hospital readmission rates.

Point-of-care ultrasound in geriatrics: a national survey of VA medical centers.

BACKGROUND: Point-of-care ultrasound (POCUS) can aid geriatricians in caring for complex, older patients. Currently, there is limited literature on POCUS use by geriatricians. We conducted a national survey to assess current POCUS use, training desired, and barriers among Geriatrics and Extended Care ("geriatric") clinics at Veterans Affairs Medical Centers (VAMCs). METHODS: We conducted a prospective observational study of all VAMCs between August 2019 and March 2020 using a web-based survey sent to all VAMC Chiefs of Staff and Chiefs of geriatric clinics. RESULTS: All Chiefs of Staff (n=130) completed the survey (100% response rate). Chiefs of geriatric clinics ("chiefs") at 76 VAMCs were surveyed and 52 completed the survey (68% response rate). Geriatric clinics were located throughout the United States, mostly at high-complexity, urban VAMCs. Only 15% of chiefs responded that there was some POCUS usage in their geriatric clinic, but more than 60% of chiefs would support the implementation of POCUS use. The most common POCUS applications used in geriatric clinics were the evaluation of the bladder and urinary obstruction. Barriers to POCUS use included a lack of trained providers (56%), ultrasound equipment (50%), and funding for training (35%). Additionally, chiefs reported time utilization, clinical indications, and low patient census as barriers. CONCLUSIONS: POCUS has several potential applications for clinicians caring for geriatric patients. Though only 15% of geriatric clinics at VAMCs currently use POCUS, most geriatric chiefs would support implementing POCUS use as a diagnostic tool. The greatest barriers to POCUS implementation in geriatric clinics were a lack of training and ultrasound equipment. Addressing these barriers systematically can facilitate implementation of POCUS use into practice and permit assessment of the impact of POCUS on geriatric care in the future.

Current Use, Training, and Barriers of Point-of-Care Ultrasound in Anesthesiology: A National Survey of Veterans Affairs Hospitals.

OBJECTIVES: The purpose of this study was to determine current use, training needs, and barriers to point-of-care ultrasound (POCUS) use among anesthesiologists in practice. DESIGN: Multicenter, prospective, observational study. SETTING: Anesthesiology departments in the Veterans Affairs Healthcare System in the United States. PARTICIPANTS: Chiefs of staff and chiefs of anesthesiology departments. INTERVENTIONS: A web-based survey was conducted between June 2019 and March 2020. Chiefs of staff answered questions about facility-level POCUS use, training, competency, and policies. Anesthesiology chiefs responded to a follow-up survey with specialty-specific POCUS questions. The results of the 2020 survey were compared with a similar survey conducted by the authors' group in 2015. MEASUREMENTS AND MAIN RESULTS: All chiefs of staff (n = 130) and 77% of anesthesiology chiefs (n = 96) completed the survey. The most common POCUS applications used were central and peripheral vascular access (69%-72%), peripheral nerve blocks (66%), and evaluation of cardiac function (29%-31%). Compared with 2015, there was a statistically significant increase in desire for training (p = 0.00015), but no significant change in POCUS use (p = 0.31). Training was most desired for volume-status assessment (52%), left ventricular function (47%), pneumothorax (47%), central line placement (40%), peripheral nerve blocks (40%), and pleural effusion (40%). The most common barriers to POCUS use were lack of funding for training (35%), trained providers (33%), and training opportunities (28%). CONCLUSIONS: A significant increase in desire for POCUS training was seen among anesthesiologists practicing in the Veterans Affairs healthcare system since 2015, and lack of training continues to be a top barrier for POCUS use among anesthesiologists.

Development of a Point-of-Care Ultrasound Track for Internal Medicine Residents.

BACKGROUND: Point-of-care ultrasound (POCUS) training has been increasing among internal medicine (IM) residency programs, but few programs can provide longitudinal training due to barriers such as lack of trained faculty. AIM: Describe the development of a longitudinal POCUS track for IM residents using local and external resources, including a national POCUS certificate program. SETTING: University-based IM residency program affiliated with a public and veterans affairs hospital. PARTICIPANTS: Twelve IM residents from 2018 to 2021. PROGRAM DESCRIPTION: Residents complete a national POCUS certificate program by attending live courses and completing online modules, an image portfolio, and final knowledge/skills assessments. Locally, residents participate in 1-month procedure and diagnostic POCUS rotations and provide peer-to-peer POCUS teaching of residents and medical students. PROGRAM EVALUATION: The POCUS track increased residents' use and comfort with diagnostic and procedural applications. All residents rated being satisfied or very satisfied with the track and would recommend it to prospective applicants (100%). The most commonly reported barriers to utilizing POCUS per residents were time constraints (83%), lack of available ultrasound equipment (83%), and lack of trained faculty (58%). DISCUSSION: IM residency programs with limited faculty expertise in POCUS can leverage external resources to provide longitudinal POCUS training to its residents.

Evidence based processes to prevent readmissions: more is better, a ten-site observational study.

BACKGROUND: 30-day hospital readmissions are an indicator of quality of care; hospitals are financially penalized by Medicare for high rates. Numerous care transition processes reduce readmissions in clinical trials. The objective of this study was to examine the relationship between the number of evidence-based transitional care processes used and the risk standardized readmission rate (RSRR). METHODS: Design: Mixed method, multi-stepped observational study. Data collection occurred 2014-2018 with data analyses completed in 2021. SETTING: Ten VA hospitals, chosen for 5-year trend of improving or worsening RSRR prior to study start plus documented efforts to reduce readmissions. PARTICIPANTS: During five-day site visits, three observers conducted semi-structured interviews (n = 314) with staff responsible for care transition processes and observations of care transitions work (n = 105) in inpatient medicine, geriatrics, and primary care. EXPOSURE: Frequency of use of twenty recommended care transition processes, scored 0-3. Sites' individual process scores and cumulative total scores were tested for correlation with RSRR. OUTCOME: best fit predicted RSRR for quarter of site visit based on the 21 months surrounding the site visits. RESULTS: Total scores: Mean 38.3 (range 24-47). No site performed all 20 processes. Two processes (pre-discharge patient education, medication reconciliation prior to discharge) were performed at all facilities. Five processes were performed at most facilities but inconsistently and the other 13 processes were more varied across facilities. Total care transition process score was correlated with RSRR (R2 = 0..61, p < 0.007). CONCLUSIONS: Sites making use of more recommended care transition processes had lower RSRR. Given the variability in implementation and barriers noted by clinicians to consistently perform processes, further reduction of readmissions will likely require new strategies to facilitate implementation of these evidence-based processes, should include consideration of how to better incorporate activities into workflow, and may benefit from more consistent use of some of the more underutilized processes including patient inclusion in discharge planning and increased utilization of community supports. Although all facilities had inpatient social workers and/or dedicated case managers working on transitions, many had none or limited true bridging personnel (following the patient from inpatient to home and even providing home visits). More investment in these roles may also be needed.

Perfusion Cultivation of Artificial Liver Extracellular Matrix in Fibrous Polymer Sponges Biomimicking Scaffolds for Tissue Engineering.

A major challenge in tissue engineering and artificial scaffolding is to combine easily tunable scaffolds biomimicking the extracellular matrix of native organs with delivery-controlled cell culturing to create fully cellularized, large artificial 3D scaffolds. Aiming at bioartificial liver construction, we present our research using galactose-functionalized, ultraporous polylactide 3D nanofiber sponges fabricated out of electrospun fibers. Sponge biomodification by blend galactosylation and in-solution coating is performed, respectively, using a polylactide-galactose carrier-copolymer that promotes cell delivery and features a pronounced autofluorescence. It allows us to verify the galactosylation success, evaluate its quality, and record dye-free, high-resolution images of the sponge network using confocal laser scanning microscopy. The galactose carrier and its impact on scaffold cellularization is validated in benchmark to several reference systems. Verification of the human hepatic cell asialoglycoprotein receptor presence and galactose interaction in culture is performed by Cu2+ receptor-blocking experiments. The culture results are extensively investigated in and ex situ to trace and quantify the cell culture progress, cell activity, and viability at different culture stages. Bioreactor cultivation of sponges reveals that the galactose carrier does not only facilitate cell adhesion but also enhances cellular distribution throughout the scaffold. The promising 3D culture results allow us to move forward to create mature in vitro liver model research systems. The elaboration into ex vivo testing platforms could help judging native cell material interactions with drugs or therapeutics, without the need of direct human or animal testing.

Teaching vs learning: Impact of deliberate practice and formative feedback on developing point of care ultrasound skills.

PURPOSE: The study investigators hypothesized that Point of Care Ultrasound (POCUS) training through bolus didactic and workshop experiences may be sufficient for trainees to learn the cognitive aspects, while an extended period of exposure with formative feedback is responsible for developing the psychomotor skills critical for POCUS. METHODS: The investigators studied trainees over the course of an academic year. They compared trainees' performance on written (cognitive) and observed image acquisition (psychomotor) exams at baseline and at each subsequent quarter, using a stepped-wedge design. They performed linear regression analysis to determine which variables contributed to knowledge and psychomotor skill development. RESULTS: Twenty-six trainees met the study requirements and participated in the POCUS curriculum. Participating in a POCUS rotation was consistently associated with an increase in psychomotor scores. There was no consistent variable to predict an increase in trainee's score on written knowledge assessments. CONCLUSIONS: Extended exposure to POCUS over a 4-week rotation with direct and indirect formative feedback can explain difference in scores on psychomotor skills assessments. Trainees scored similarly on the written assessment with or without a POCUS rotation. Training through didactic and workshop experiences may be sufficient to learn the cognitive aspects, but not psychomotor skills required for POCUS.

Ultraporous, Compressible, Wettable Polylactide/Polycaprolactone Sponges for Tissue Engineering.

Ultraporous, degradable sponges made of either polylactide or of blends of polylactide/poly(ε-caprolactone) are prepared by freeze-drying of dispersions of short electrospun fibers and subsequent thermal annealing. The sponges feature ultrahigh porosity (99.6%), a hierarchical cellular structure, and high reversible compressibility with fast recovery from deformation in the dry as well as in the wet state. The sponge properties depend on the fiber dispersion concentration and the annealing temperature. Sponge characteristics like fiber density (2.5-20 mg/cm3), size, shape, crystallinity, mechanical strength, wetability, and structural integrity are user adjustable. Cell culture experiments were successfully performed with Jurkat cells with Confocal Laser Scanning Microscopy and MTT staining showing rapid cell proliferation. Live/Dead staining demonstrated high viability of the seeded cells. The sponge characteristics and modifications investigated and presented here reveal that these sponges are highly promising for tissue engineering applications.

Community Clinicians and the Veterans Choice Program for PTSD Care: Understanding Provider Interest During Early Implementation.

BACKGROUND: In 2014, the Department of Veterans Affairs (VA) implemented the Veterans Choice Program (VCP) to provide reimbursement for community-based care to eligible veterans. Inadequate networks of participating providers may impact the utility of VCP for veterans with posttraumatic stress disorder (PTSD), a complex condition occurring at lower frequency among civilians. OBJECTIVES: To compare characteristics and attitudes of community-based primary care and mental health providers reporting interest or no interest in VCP participation during early implementation; and to examine perceptions and experiences of VCP among "early adopters." RESEARCH DESIGN: Cross-sectional surveys with 2 samples: a stratified random sample of mental health and primary care prescribers and psychotherapists drawn from state licensing boards (Community Sample); and a stratified random sample of prescribers and psychotherapists identified as VCP-authorized providers (VCP-Authorized). SUBJECTS: Five hundred fifty-three respondents in the Community Sample and 115 in the VCP-Authorized (total, n=668; 21.1% response). MEASURES: Surveys assessed provider and practice characteristics, attitudes to VA and VCP, and experiences and satisfaction with the VCP; an open-ended survey item assessed providers' reasons for interest or lack of interest in VCP participation. RESULTS: Few providers reported VCP participation during this period. Interest in VCP participation was associated across provider groups with factors including being a veteran and receiving VA reimbursement; currently providing treatment for PTSD was associated with interest in VCP participation among psychotherapists, but not prescribers. CONCLUSIONS: Developing networks of VCP providers to serve Veterans with PTSD is likely to require targeting more receptive provider groups, reducing barriers to participation, and more effectively communicating the value of VCP participation to providers.

Gliptin and GLP-1 analog treatment improves survival and vascular inflammation/dysfunction in animals with lipopolysaccharide-induced endotoxemia.

Dipeptidyl peptidase (DPP)-4 inhibitors are used to treat hyperglycemia by increasing the incretin glucagon-like peptide-1 (GLP-1). Previous studies showed anti-inflammatory and antiatherosclerotic effects of DPP-4 inhibitors. Here, we compared the effects of linagliptin versus sitagliptin and liraglutide on survival and vascular function in animal models of endotoxic shock by prophylactic therapy and treatment after lipopolysaccharide (LPS) injection. Gliptins were administered either orally or subcutaneously: linagliptin (5 mg/kg/day), sitagliptin (50 mg/kg/day) or liraglutide (200 µg/kg/day). Endotoxic shock was induced by LPS injection (mice 17.5-20 mg/kg i.p., rats 10 mg/kg/day). Linagliptin and liraglutide treatment or DPP-4 knockout improved the survival of endotoxemic mice, while sitagliptin was ineffective. Linagliptin, liraglutide and sitagliptin ameliorated LPS-induced hypotension and vascular dysfunction in endotoxemic rats, suppressed inflammatory parameters such as whole blood nitrosyl-iron hemoglobin (leukocyte-inducible nitric oxide synthase activity) or aortic mRNA expression of markers of inflammation as well as whole blood and aortic reactive oxygen species formation. Hemostasis (tail bleeding time, activated partial thromboplastin time) was impaired in endotoxemic rats and recovered under cotreatment with linagliptin and liraglutide. Finally, the beneficial effects of linagliptin on vascular function and inflammatory parameters in endotoxemic mice were impaired in AMP-activated kinase (alpha1) knockout mice. The improved survival of endotoxemic animals and other data shown here may warrant further clinical evaluation of these drugs in patients with septic shock beyond the potential improvement of inflammatory complications in diabetic individuals with special emphasis on the role of AMP-activated kinase (alpha1) in the DPP-4/GLP-1 cascade.

Gaining consensus on a protocol for general surgery physician assistants in the management of non-compressible abdominal haemorrhage in military austere environments: a Delphi study.

BACKGROUND: Non-compressible abdominal haemorrhage (NCAH) is a potentially preventable cause of death due to injury. Limited exploratory laparotomy by a non-surgeon is a temporary intervention to sustain life until definitive surgical intervention by trauma surgeons can be obtained. This study aims to establish consensus on a protocol for general surgery physician assistants performing limited exploratory laparotomy to manage NCAH in an austere environment. METHOD: This study included anonymised trauma surgeons and general surgery physician assistants from military and civilian backgrounds. Participants were recruited from various professional surgical organisations, including direct interaction with trauma surgeons and surgical physician assistants. Participants used a modified Delphi survey with a 9-point Likert scale in two rounds. The two surveys were categorised into three parts: protocol for NCAH (part A), the potential role of general surgery physician assistants (part B) and measures of success (part C). A total of 24 statements were voted on and assessed. Votes were divided into three zones: agreement (median 7-9), uncertain (median 4-6) and disagreement (median 1-3). To reach a consensus, 70% agreement was required within a zone. If more than 30% of the votes fell outside of a specific zone, consensus was not achieved. After consensus, the original protocol was revised in an online meeting with experts. RESULTS: The initial analysis involved 29 participants. After 2 survey rounds, 19 out of 24 statements reached a consensus. Part A: 10 statements gained consensus, including in austere environments, controlling NCAH can be challenging. A qualified general surgery physician assistant should intervene. A focused assessment with sonography for trauma examination can be used for screening. Bleeding can be managed with packing and pressure. After managing the haemorrhage, the abdominal wall should be left open with a temporary closure technique. Part B: nine statements gained consensus, including in austere locations, a licensed general surgery physician assistant with a minimum of 3 years of experience working under the supervision of a trauma/general surgeon can perform interventions for limited exploratory laparotomy for patients with NCAH. Part C: general surgery physician assistants will be required to have the same success rates as any qualified surgeon. CONCLUSION: Gaining consensus and implementing a revised protocol for managing NCAH by general surgery physician assistants is attainable. General surgery physician assistants will need formal training to manage NCAH. With the support of trauma surgeons who provide direct and indirect supervision, general surgery physician assistants can develop a comprehensive understanding of the necessary skills and make sound decisions when treating patients with this condition. This teamwork can also increase surgical capacity and potentially decrease mortality rates for patients with NCAH in austere environments.

The impact of intravenous versus submucosal dexamethasone on short-term patient response: A randomized controlled trial.

BACKGROUND: The purpose of this randomized, cross-over trial was to determine if a preoperative dose of dexamethasone administered submucosally is as effective as intravenous (IV) dexamethasone in reducing pain, swelling, and analgesic consumption after periodontal flap surgery. METHODS: Thirty-nine patients planned for two similar flap surgeries under IV sedation were included. Before the first surgery, patients were randomized to receive 8 mg of IV or submucosal dexamethasone. Via the alternate route, 0.9% sodium chloride (placebo) was administered. Dexamethasone was administered via the opposite route during the second surgery. A standardized regimen of 600 mg ibuprofen and 325 mg acetaminophen was used to manage postoperative pain. Patients recorded pain and swelling levels on a 21-point numerical rating scale (NRS-21) and a four-point visual rating scale (VRS-4), as well as analgesic usage via a phone application at 12, 24, 48, 72, and 168 h postoperatively. RESULTS: While NRS-21 and VRS-4 data suggest a trend toward decreased pain and swelling with IV administration, there were no significant differences in analgesic usage or pain at any time and a significant difference in swelling only at 72 h in favor of IV administration (p = 0.047). CONCLUSIONS: There was no significant difference in pain or analgesic usage following periodontal flap surgery comparing IV and submucosal dexamethasone. A statistically significant difference in swelling between groups at 72 h is likely of limited clinical relevance. Submucosal dexamethasone is an effective way to mitigate pain following periodontal surgery, particularly when IV access for sedation is not required.

Resistance to high-fat diet-induced weight gain in transgenic mice overexpressing human wild-type α-synuclein: A model for metabolic dysfunction in Parkinson's disease.

Unintentional weight loss, primarily due to the loss of fat mass rather than muscle mass, is common among patients with Parkinson's disease (PD) and is associated with poor quality of life and accelerated disease progression. Since transgenic mice overexpressing human wild-type α-synuclein (α-Syn mice) are modestly leaner than control mice, and since diabetes, a metabolic disorder, is a major risk factor for PD, we reasoned that high-fat diet-induced diabetes/metabolic dysregulation in α-Syn mice may serve as a robust tool for exploring how early α-synuclein pathology contributes to metabolic dysregulation, leading to weight loss in PD. Thus, α-Syn and age-matched controls were fed a high-fat diet (HFD) chow (60% fat calories) ad libitum for four months. Compared with controls on HFD (control-HFD), α-Syn mice on HFD (α-Syn-HFD) were dramatically leaner. The resistance to gaining weight in α-Syn-HFD mice was accompanied by improved glucose tolerance, a dramatic decrease in fat mass, and an increase in energy expenditure. Despite this leaner phenotype and better glucose tolerance, the mortality was much higher in male α-Syn-HFD mice than in all controls, but was unaffected in females, suggesting protective effects of female sex hormones, as well as lower α-synuclein levels. Immunoblot analysis of insulin signaling in the olfactory bulb, the proposed initial seeding site of α-synuclein pathology, revealed a decrease of IGF-IRß, p GSK, and p mTOR in α-Syn-HFD mice. Since GSK-3ß and mTOR regulate synaptic plasticity, we assessed levels of PSD-95 and synaptophysin in the olfactory bulb. As anticipated, we observed a significant decrease in the levels of PSD-95, along with a potentially compensatory increase in synaptophysin levels. Our results show that α-Syn mice, when challenged with diet-induced diabetes/metabolic dysregulation, clearly reveal a profile of robust metabolic dysfunction, thus providing a sensitive tool for assessing the underlying mechanism of metabolic dysfunction and its impact on weight loss and disease progression in PD. We propose a role for olfactory dysfunction in PD-related unintentional weight loss and suggest that strategies aimed at increasing body weight/BMI will improve the quality of life and prognosis for people living with PD.

The Impact of Time From Diagnosis to Initiation of Chemotherapy on Survival of Patients With Newly Diagnosed Diffuse Large B-Cell Lymphoma in the Veterans Health Administration.

INTRODUCTION: Our retrospective study evaluates the impact of time from diagnosis to treatment (TDT) on outcomes of patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) treated within the Veterans Health Administration (VHA). METHODS: VHA patients diagnosed with DLBCL between 2011 and 2019 were included, while those with primary central nervous system lymphoma were excluded. The median overall survival and progression-free survival were estimated with the Kaplan-Meier method. Univariate, bivariate, and multivariable analyses were performed using the Cox proportional hazards model. The odds ratio for refractory outcomes was calculated using logistic regression. RESULTS: A total of 2448 patients were included. The median time from diagnosis to treatment of the cohort was 19 days. When comparing median progression-free survival, median overall survival, and the 2-year overall survival between the group that started treatment within 1 week and each of the other groups individually, there was a significant difference favoring improved survival in all groups with a TDT longer than 1 week (P < .0001). These patients also had a lower odds ratio for refractory outcomes. On multivariable analysis, TDT remained an independent prognostic factor. CONCLUSION: Our study shows that a TDT equal to or less than 1 week is associated with adverse clinical factors, worse outcomes, and response in DLBCL, even after adjusting for multiple known poor prognostic factors. This was the first time that response to first-line therapy was correlated to time to treatment. Our findings support ongoing efforts to improve currently standardized prognostic tools and the incorporation of TDT into clinical trials to avoid selection bias.