Adjuvant imatinib in high-risk resected gastrointestinal stromal tumors: Merely delaying the inevitable?

INTRODUCTION: Patients with high-risk resected gastrointestinal stromal tumors (GIST) receiving adjuvant imatinib have improved recurrence-free survival (RFS), however whether a complete cytocidal effect exists is unknown. We investigated this using a normalized recurrence timeline measured from end of oncologic treatment (EOOT), defined as the later of resection or end of adjuvant therapy. METHODS: We reviewed patients with resected high-risk GIST at our cancer center from 2003 to 2018. RFS (measured from resection and EOOT), overall survival (OS), and time to imatinib resistance (TTIR) were analyzed using Kaplan-Meier analysis and multivariable Cox proportional hazards modeling. The performance of the Memorial Sloan Kettering (MSK) GIST nomogram was assessed. RESULTS: We identified 86 patients with high-risk GIST with a median 106 months of postsurgical follow-up. One-third (n = 29; 34%) did not receive adjuvant imatinib, while 57 (66%) did for a median of 3 years. The MSK nomogram-predicted 5-year RFS for patients receiving adjuvant imatinib was similar to those who did not (29% vs. 31%, p = 0.64). When RFS was measured from EOOT, the MSK-predicted RFS was independently associated with EOOT RFS (hazard ratio 0.22, p = 0.02), while adjuvant imatinib receipt and duration were not. Neither receipt nor duration of adjuvant imatinib were associated with TTIR or OS (all p > 0.05). CONCLUSIONS: Treatment with adjuvant imatinib delays, but does not clearly impact ultimate recurrence, TTIR, or OS, suggesting many patients with high-risk GIST may receive adjuvant imatinib unnecessarily. Additional studies are needed to establish the benefit of adjuvant therapy versus initiating therapy at first radiographic recurrence.

Presurgical pulmonary function tests in the first few days of life in neonates with congenital heart disease, a pilot study.

OBJECTIVE: To compare early pulmonary function tests (PFTs) in neonates with critical congenital heart disease (CHD) compared to a historical reference group. DESIGN: Infants ≥ 37 weeks gestation with critical CHD were studied within the first few days of life, prior to cardiac surgery, and compared to data from a published reference group of healthy term neonates without CHD, studied at the same institution. Passive respiratory resistance (Rrs) and compliance (Crs) were measured with the single breath occlusion technique following specific acceptance criteria. The study was powered for a 30% difference in Rrs. RESULTS: PFTs in 24 infants with CHD were compared to 31 historical reference infants. There was no difference in the Rrs between the groups. The infants with CHD had a significantly decreased Crs (1.02 ± 0.26 mL/cmH2O/kg versus 1.32 ± 0.36; (p < 0.05; mean ± SD)). CONCLUSIONS: Further prospective studies are required to quantify early PFTs in infants with CHD of different phenotypes.

Gingivoperiosteoplasty in Children with Cleft Lip and Palate: The Need for Alveolar Bone Grafting.

OBJECTIVE: This study aimed to determine the efficacy of gingivoperiosteoplasty (GPP) in preventing alveolar bone grafting (ABG) among children with cleft lip and palate (CLP). DESIGN/SETTING: Retrospective university hospital single center study. PATIENTS: Children with CLP treated with GPP from 2000-2015 were included. Those under eight years of age, without definitive conclusions regarding need for ABG or with incomplete data were excluded. INTERVENTIONS: Included patients were analyzed for demographics, cleft type, age at GPP, associated cleft surgery, use of nasoalveolar molding (NAM), indication for ABG, operating surgeon and presence of residual alveolar fistula. T-tests and Fisher's exact tests were utilized for statistical analysis. MAIN OUTCOME MEASURE: The need for ABG. RESULTS: Of the 1682 children identified with CLP, 64 underwent GPP and met inclusion criteria. 78% of patients with CLP who underwent GPP were recommended for ABG. Those who received GPP at a younger age (P = .004) and at the time of initial cleft lip repair (P = .022) were less likely to be recommended for ABG. Patients with complete CLP were more likely to be recommended for ABG than patients with cleft lip and alveolus only (P = .015). The operating surgeon impacted the likelihood of ABG (P = .004). Patient gender, race, ethnicity, laterality, and NAM were not significantly associated with recommendation for ABG. CONCLUSION: GPP does not preclude the need for ABG. Therefore, the success of ABG after GPP and maxillary growth restriction should be analyzed further to determine if GPP is a worthwhile adjunct to ABG in cleft care.

Presurgical Pulmonary Function Tests in the First Few Days of Life in Neonates with Congenital Heart Disease, A Pilot Study.

Objective: To compare early pulmonary function tests (PFTs) in neonates with critical congenital heart disease (CHD) compared to a historical reference group. Design: Infants > 37 weeks gestation with critical CHD were studied within the first few days of life and prior to cardiac surgery and compared to data from a published reference group. Passive respiratory resistance (Rrs) and compliance (Crs) were measured with the single breath occlusion technique following specific acceptance criteria. The study was powered for a 30% difference in Rrs. Results: PFTs in 24 infants with CHD were compared to 31 historical reference infants. There was no difference in the Rrs between the groups. The infants with CHD had a significantly decreased Crs (1.02 ± 0.26 mL/cmH2O/kg versus 1.32 ± 0.36; (p < 0.05; mean ± SD)). Conclusions: Further prospective studies are required to quantify early PFTs in infants with CHD of different phenotypes.

Association of fibrinolysis phenotype with patient outcomes following traumatic brain injury.

BACKGROUND: Impaired coagulation is associated with elevated risk of mortality in trauma patients. Prior studies have demonstrated increased mortality in patients with hyperfibrinolysis (HF) and fibrinolysis shutdown (SD). In addition, prior studies have demonstrated no effect of tranexamic acid (TXA) on fibrinolysis phenotypes. We examined the association of admission fibrinolysis phenotype with traumatic brain injury (TBI) patient outcomes. METHODS: Data were extracted from a placebo-controlled multicenter clinical trial. Patients ≥15 years with TBI (Glasgow Coma Scale score, 3-12) and systolic blood pressure ≥90 mm Hg were randomized in the out-of-hospital setting to receive placebo bolus/placebo infusion (Placebo), 1 gram (g) TXA bolus/1 g TXA infusion (bolus maintenance [BM]); or 2 g TXA bolus/placebo infusion (bolus only [BO]). Fibrinolysis phenotypes on admission were determined by clot lysis at 30 minutes (LY30): SD, ≤0.8%; physiologic, 0.9% to 2.9%; HF, ≥3%. Logistic regression was used to control for age, sex, penetrating injury, Injury Severity Score, maximum head AIS, and TXA treatment group. RESULTS: Seven hundred forty-seven patients met inclusion criteria. Fibrinolysis shutdown was the most common phenotype in all treatment groups and was associated with increased age, Injury Severity Score, and presence of intracranial hemorrhage (ICH). Inpatient mortality was 15.2% for SD and HF, and 10.6% for physiologic ( p = 0.49). No differences in mortality, disability rating scale at 6 months, acute kidney injury, acute respiratory distress syndrome, or multi-organ failure were noted between fibrinolysis phenotypes. CONCLUSION: SD is the most common phenotype expressed in moderate to severe TBI. In TBI, there is no association between fibrinolysis phenotype and mortality or other major complications. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

Referral and treatment patterns in pancreatic acinar cell carcinoma: A regional population-level analysis.

BACKGROUND: Pancreatic acinar cell carcinoma (PACC) is a rare exocrine tumor of the pancreas. We evaluated the effect disease stage, surgical intervention, and institutional volume status plays in survival. METHODS: We queried the Oregon State Cancer Registry for patients with PACC from 1997 to 2018. Treatment and referral patterns were analyzed, and overall survival (OS) was evaluated with Kaplan-Meier and Cox-proportional hazard analysis. RESULTS: 43 patients were identified. Median OS was 33.1 and 7.1 months in those with locoregional and metastatic disease respectively (p â€‹= â€‹0.008). Surgical intervention was associated with improved OS (hazard ratio 0.28, p â€‹< â€‹0.0001). High volume center (HVC) care trended towards improving OS. While the majority of cases were diagnosed at low volume centers (74%), referral to HVCs was rare (n â€‹= â€‹4) and limited to advanced (stage III/IV) disease. CONCLUSION: Stage and surgical resection influence survival outcomes in PACC, more data is needed to delineate the impact of institutional volume status.

Modeling and Remodeling the Cell: How Digital Twins and HCMV Can Elucidate the Complex Interactions of Viral Latency, Epigenetic Regulation, and Immune Responses.

Purpose of Review: Human cytomegalovirus (HCMV), while asymptomatic in most, causes significant complications during fetal development, following transplant or in immunosuppressed individuals. The host-virus interactions regulating viral latency and reactivation and viral control of the cellular environment (immune regulation, differentiation, epigenetics) are highly complex. Understanding these processes is essential to controlling infection and can be leveraged as a novel approach for understanding basic cell biology. Recent Findings: Immune digital twins (IDTs) are digital simulations integrating knowledge of human immunology, physiology, and patient-specific clinical data to predict individualized immune responses and targeted treatments. Recent studies used IDTs to elucidate mechanisms of T cells, dendritic cells, and epigenetic control-all key to HCMV biology. Summary: Here, we discuss how leveraging the unique biology of HCMV and IDTs will clarify immune response dynamics, host-virus interactions, and viral latency and reactivation and serve as a powerful IDT-validation platform for individualized and holistic health management.

Comparative polar and lipid plasma metabolomics differentiate KSHV infection and disease states.

BACKGROUND: Kaposi sarcoma (KS) is a neoplastic disease etiologically associated with infection by the Kaposi sarcoma-associated herpesvirus (KSHV). KS manifests primarily as cutaneous lesions in individuals due to either age (classical KS), HIV infection (epidemic KS), or tissue rejection preventatives in transplantation (iatrogenic KS) but can also occur in individuals, predominantly in sub-Saharan Africa (SSA), lacking any obvious immune suppression (endemic KS). The high endemicity of KSHV and human immunodeficiency virus-1 (HIV) co-infection in Africa results in KS being one of the top 5 cancers there. As with most viral cancers, infection with KSHV alone is insufficient to induce tumorigenesis. Indeed, KSHV infection of primary human endothelial cell cultures, even at high levels, is rarely associated with long-term culture, transformation, or growth deregulation, yet infection in vivo is sustained for life. Investigations of immune mediators that distinguish KSHV infection, KSHV/HIV co-infection, and symptomatic KS disease have yet to reveal consistent correlates of protection against or progression to KS. In addition to viral infection, it is plausible that pathogenesis also requires an immunological and metabolic environment permissive to the abnormal endothelial cell growth evident in KS tumors. In this study, we explored whether plasma metabolomes could differentiate asymptomatic KSHV-infected individuals with or without HIV co-infection and symptomatic KS from each other. METHODS: To investigate how metabolic changes may correlate with co-infections and tumorigenesis, plasma samples derived from KSHV seropositive sub-Saharan African subjects in three groups, (A) asymptomatic (lacking neoplastic disease) with KSHV infection only, (B) asymptomatic co-infected with KSHV and HIV, and (C) symptomatic with clinically diagnosed KS, were subjected to analysis of lipid and polar metabolite profiles RESULTS: Polar and nonpolar plasma metabolic differentials were evident in both comparisons. Integration of the metabolic findings with our previously reported KS transcriptomics data suggests dysregulation of amino acid/urea cycle and purine metabolic pathways, in concert with viral infection in KS disease progression. CONCLUSIONS: This study is, to our knowledge, the first to report human plasma metabolic differentials between in vivo KSHV infection and co-infection with HIV, as well as differentials between co-infection and epidemic KS.

γ' fibrinogen levels as a biomarker of COVID-19 respiratory disease severity.

Coronavirus disease 2019 (COVID-19) is characterized by a pro-inflammatory state associated with organ failure, thrombosis, and death. We investigated a novel inflammatory biomarker, γ' fibrinogen (GPF), in 103 hospitalized patients with COVID-19 and 19 healthy controls. We found significant associations between GPF levels and the severity of COVID-19 as judged by blood oxygen saturation (SpO2). The mean level of GPF in the patients with COVID-19 was significantly higher than in controls (69.8 (95 % CI 64.8-74.8) mg/dL compared with 36.9 (95 % CI 31.4-42.4) mg/dL, p < 0.0001), whereas C-reactive protein (CRP), lactate dehydrogenase (LDH), and total fibrinogen levels were not significantly different between groups. Mean GPF levels were significantly highest in patients with severe COVID-19 (SpO2 ≤ 93 %, GPF 75.2 (95 % CI 68.7-81.8) mg/dL), compared to mild/moderate COVID-19 (SpO2 > 93 %, GPF 62.5 (95 % CI 55.0-70.0) mg/dL, p = 0.01, AUC of 0.68, 95 % CI 0.57-0.78; Youden's index cutpoint 62.9 mg/dL, sensitivity 0.64, specificity 0.63). In contrast, CRP, interleukin-6, ferritin, LDH, D-dimers, and total fibrinogen had weaker associations with COVID-19 disease severity (all ROC curves with lower AUCs). Thus, GPF may be a useful inflammatory marker of COVID-19 respiratory disease severity.

Neoadjuvant therapy does not impact the biliary microbiome in patients with pancreatic cancer.

BACKGROUND: Pancreatic adenocarcinoma (PDAC) often impinges on the biliary tree and obstruction necessitates stent placement increasing the risk of surgical site infections (SSIs). We sought to explore the impact of neoadjuvant therapy on the biliary microbiome and SSI risk in patients undergoing resection. METHODS: A retrospective analysis was performed on 346 patients with PDAC who underwent resection at our institution from 2008 to 2021. Univariate and multivariate methods were utilized for analysis. RESULTS: Biliary stenting rates were similar between groups but resulted in increased bile culture positivity (97% vs. 15%, p < 0.001). Culture positivity did not differ between upfront resection or neoadjuvant chemotherapy (NAC) (77% vs. 80%, p = 0.60). NAC-alone versus neoadjuvant chemoradiotherapy did not impact biliary positivity (80% vs. 79%, p = 0.91), nor did 5-fluorouracil versus gemcitabine-based regimens (73% vs. 85%, p = 0.19). While biliary stenting increased incisional SSI risk (odds ratios [OR]: 3.87, p = 0.001), NAC did not (OR: 0.83, p = 0.54). Upfront resection, NAC, and chemoradiotherapy were not associated with biliary organism-specific changes or antibiotic resistance patterns. CONCLUSIONS: Biliary stenting is the greatest predictor for positive biliary cultures and SSIs in resected PDAC patients. Neither NAC nor radiotherapy impact bile culture positivity, speciation, rates, or antibiotic resistance patterns, and perioperative antibiotic prophylaxis should not differ.

High-volume centers are associated with higher receipt of combined therapy in stage III pancreatic cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed at a locally advanced stage with vascular involvement which was previously viewed as a contraindication to resection. However, high-volume centers are increasingly capable of resecting complex tumors. We aimed to explore patterns of treatment that are uncharacterized on a population level. METHODS: A statewide registry was queried from 2003 to 2018 for stage III PDAC. Stepwise logistic regression and Kaplan-Meier were used for statistical analysis. RESULTS: We identified 424 eligible patients. 348 (82%) received chemotherapy, 17 (4.0%) received resection, and 59 (13.9%) received both; median survival was 10.7, 8.7, and 22.7 months, respectively (P < 0.001). High-volume centers (≥20 cases per year; OR 5.40 [95% CI: 2.76, 10.58], P < 0.001) and later year of diagnosis (OR 1.12/year [95% CI: 1.04, 1.20], P = 0.004) were associated with higher odds of receiving combined therapy. CONCLUSION: PDAC patients with vascular involvement who receive both systemic chemotherapy and surgical resection have improved overall survival. High-volume centers are independently associated with higher odds of receiving combined systemic therapy and surgical resection.

Evaluation of a Plastic and Reconstructive Surgery Resident Non-surgical Cosmetic Clinic Experience.

INTRODUCTION: An important component of plastic surgery residency training is independent cosmetic patient management. A resident cosmetic clinic was created at Oregon Health & Science University in 2007 to expand this experience. The cosmetic clinic has traditionally been most successful in offering nonsurgical facial rejuvenation with neuromodulators and soft tissue fillers. This study focuses on the demographics of the patient population and the treatments provided over a 5-year period and compares this experience to those of the same program's attending cosmetic clinics. METHODS: A retrospective chart review of all patients seen at Oregon Health & Science University's Plastic and Reconstructive Surgery Resident Cosmetic Clinic between January 1, 2017, and December 31, 2021 was performed. Patient demographics, type of injectable received (neuromodulator versus soft tissue filler), location of injection, and additional cosmetic procedures were evaluated. RESULTS: Two hundred patients met the study criteria, which included 114 seen in the resident clinic (RC), 31 seen in attending clinic (AC), and 55 patients seen in both. A primary analysis compared the two groups seen in the resident and attending only clinics. The average age of patients seen in the RC was younger, 45 versus 51.5 (P ≤ 0.05). There was a trend toward more patients in the RC being involved in healthcare as compared to those patients seen in the AC, but this difference was not found to be statistically significant. The median number of neuromodulator visits in the RC was 2 (1, 4) versus 1 (1, 2) in the AC (P ≤ 0.05) The most common location for neuromodulator injections in both clinics was the corrugators. CONCLUSIONS: Patients in the resident cosmetic clinic were younger females, most receiving neuromodulator injections. No statistically significant differences were identified in patient population, injections received, and location of injections between the two clinics, indicating a similar trainee skill set and patient care plan between the two clinics.

Collection of Plasma Samples in Areas with Limited Healthcare Access.

Regular monitoring of various biomarkers and molecular panels in plasma can significantly help to prevent disease onset and improve its management and final outcomes. Many groups can benefit from monitoring programs focusing on the prevention of cardiovascular diseases, evaluation of environmental exposure impacts, or the prevention/management of cancer. Improvement in therapeutic options in part due to targeted therapeutic agents and monoclonal antibody therapies has led to a significant sized population that can be described as "cancer survivors." These patients, although in remission from their original disease, are at significant risk for the recurring disease and must be monitored for adverse events. Monitoring is, however, not an easy task; requiring a high level of complexity in lab facilities and blood/plasma sampling, collection, and storage must occur under tightly controlled conditions. These demanding circumstances are especially difficult to attain in rural areas and in historically marginalized populations. The Telimmune Plasma Separation Card (TPS card or TPSC) has been developed to enable diagnostic plasma sampling, collection, and stabilization in locations that may be remote to laboratory or clinic. The TPSC requires a drop of blood applied to a top of a separation system consisting of a separation membrane and collection disk. In 3 min, the TPSC device separates plasma from erythrocytes and deposits a defined volume of plasma into a collection disc which is air-dried for 15 min to deliver a stabilized, volumetric plasma sample, which may be stored or shipped at ambient temperatures with minimal biological risk. Extraction of proteins and metabolites is then achieved in well-equipped laboratories using protocols discussed in this chapter.

Socioeconomic and Geographic Disparities in the Referral and Treatment of Pancreatic Cancer at High-Volume Centers.

Importance: Treatment at high-volume centers (HVCs) has been associated with improved overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC); however, it is unclear how patterns of referral affect these findings. Objective: To understand the relative contributions of treatment site and selection bias in driving differences in outcomes in patients with PDAC and to characterize socioeconomic factors associated with referral to HVCs. Design, Setting, Participants: A population-based retrospective review of the Oregon State Cancer Registry was performed from 1997 to 2019 with a median 4.3 months of follow-up. Study participants were all patients diagnosed with PDAC in Oregon from 1997 to 2018 (n = 8026). Exposures: The primary exposures studied were diagnosis and treatment at HVCs (20 or more pancreatectomies for PDAC per year), low-volume centers ([LVCs] less than 20 per year), or both. Main Outcomes and Measures: OS and treatment patterns (eg, receipt of chemotherapy and primary site surgery) were evaluated with Kaplan-Meier analysis and logistic regression, respectively. Results: Eight thousand twenty-six patients (male, 4142 [52%]; mean age, 71 years) were identified (n = 3419 locoregional, n = 4607 metastatic). Patients receiving first-course treatment at a combination of HVCs and LVCs demonstrated improved median OS for locoregional and metastatic disease (16.6 [95% CI, 15.3-17.9] and 6.1 [95% CI, 4.9-7.3] months, respectively) vs patients receiving HVC only (11.5 [95% CI, 10.7-12.3] and 3.9 [95% CI, 3.5-4.3] months, respectively) or LVC-only treatment (8.2 [95% CI, 7.7-8.7] and 2.1 [95% CI, 1.9-2.3] months, respectively; all P < .001). No differences existed in disease burden by volume status of diagnosing institution. When stratifying by site of diagnosis, HVC-associated improvements in median OS were smaller (locoregional: 10.4 [95% CI, 9.5-11.2] vs 9.9 [95% CI, 9.4-10.4] months; P = .03; metastatic: 3.6 vs 2.7 months, P < .001) than when stratifying by the volume status of treating centers, indicating selection bias during referral. A total of 94% (n = 1103) of patients diagnosed at an HVC received HVC treatment vs 18% (n = 985) of LVC diagnoses. Among patients diagnosed at LVCs, later year of diagnosis and higher estimated income were independently associated with higher odds of subsequent HVC treatment, while older age, metastatic disease, and farther distance from HVC were independently associated with lower odds. Conclusions and Relevance: LVC-to-HVC referrals for PDAC experienced improved OS vs HVC- or LVC-only care. While disease-related features prompting referral may partially account for this finding, socioeconomic and geographic disparities in referral worsen OS for disadvantaged patients. Measures to improve access to HVCs are encouraged.

Standardized perioperative care reduces colorectal surgical site infection in children: A Western Pediatric Surgery Research Consortium multicenter analysis.

PURPOSE: Surgical site infection (SSI) remains a significant source of patient morbidity and resource utilization in children undergoing colorectal surgery. We examined the utility of a protocolized perioperative care bundle in reducing SSI in pediatric patients undergoing colorectal surgery. METHODS: We conducted a prospective cohort study of patients ≤18 years of age undergoing colorectal surgery at ten United States children's hospitals. Using a perioperative care protocol comprising eight elements, or "colon bundle", we divided patients into low (1-4 elements) or high (5-8 elements) compliance cohorts. Procedures involving colorectal repair or anastomosis with abdominal closure were included. Demographics and clinical outcomes were compared between low and high compliance cohorts. Compliance was compared with a retrospective cohort. The primary outcome was superficial SSI incidence at 30 days. RESULTS: Three hundred and thirty-six patients were included in our analysis: 138 from the low compliance cohort and 198 from the high compliance cohort. Age and gender were similar between groups. Preoperative diagnosis was similar except for more patients in the high compliance cohort having inflammatory bowel disease (18.2% versus 5.8%, p<0.01). The most common procedure performed was small bowel to colorectal anastomosis. Wound classification and procedure acuity were similar between groups. Superficial SSI at 30 days occurred less frequently among the high compliance compared to the low compliance cohort (4% versus 9.7%, p = 0.036). Median postoperative length of stay and 30-day rates of readmission, reoperation, intra-abdominal abscess and anastomotic leak requiring operation were not significantly different between groups. None of the individual colon bundle elements were independently protective against superficial SSI. CONCLUSION: Standardization of perioperative care is associated with a reduction in superficial SSI in pediatric colorectal surgery. Expansion of standardized protocols for children undergoing colorectal surgery may improve outcomes and decrease perioperative morbidity. TYPE OF STUDY: Clinical Research Paper LEVEL OF EVIDENCE: Level II.

Effectiveness of a care bundle for primary prevention of intraventricular hemorrhage in high-risk neonates: a Bayesian analysis.

OBJECTIVE: To determine whether an intraventricular hemorrhage (IVH) prevention bundle featuring midline-elevated positioning reduced IVH among high-risk infants. STUDY DESIGN: In a retrospective study design, we compared outcomes of infants <1250 grams birth weight or <30 weeks gestation before (N = 205) and after (N = 360) implementation of an IVH prevention bundle, using Bayesian and frequentist logistic regression to determine whether the intervention decreased any grade IVH. RESULTS: In both the Bayesian and frequentist analyses, there was no difference in odds of any grade IVH before and after the implementation of the prevention bundle (OR 0.993; 95% Credible Interval 0.751-1.323 and OR 1.23; 95% Confidence Interval 0.818-1.864 respectively). Bias analyses suggested that these results were robust to bias from potential deaths attributable to IVH. CONCLUSION: In this retrospective analysis, we found no evidence for a protective effect of an IVH prevention bundle on IVH incidence among high-risk neonates at a level IV NICU.

Moral injury and psychosocial functioning in health care workers during the COVID-19 pandemic.

Studies of moral injury among nonmilitary samples are scarce despite repeated calls to examine the prevalence and outcomes of moral injury among civilian frontline workers. The purpose of this study was to describe the prevalence of moral injury and to examine its association with psychosocial functioning among health care workers during the COVID-19 pandemic. We surveyed health care workers (N = 480), assessing exposure to potentially morally injurious events (PMIEs) and psychosocial functioning. Data were analyzed using latent class analysis (LCA) to explore patterns of PMIE exposure (i.e., classes) and corresponding psychosocial functioning. The minimal exposure class, who denied PMIE exposure, accounted for 22% of health care workers. The moral injury-other class included those who had witnessed PMIEs for which others were responsible and felt betrayed (26%). The moral injury-self class comprised those who felt they transgressed their own values in addition to witnessing others' transgressions and feeling betrayed (11%). The betrayal-only class included those who felt betrayed by government and community members but otherwise denied PMIE exposure (41%). Those assigned to the moral injury-self class were the most impaired on a psychosocial functioning composite, followed by those assigned to the moral injury-other and betrayal-only classes, and finally the minimal exposure class. Moral injury is prevalent and impairing for health care workers, which establishes a need for interventions with health care workers in organized care settings. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Hospital Care for Adult Patients with Congenital Heart Diseases.

OBJECTIVE: The ideal type of hospital to care for adult congenital heart disease (ACHD) patients is not well known. Hospital competitiveness, clinical volume and market structure can influence clinical outcomes. We sought to understand how hospital competitiveness affects clinical outcomes in ACHD patients in the era prior to the Adult Congenital Heart Association accreditation program. METHODS: Patient discharges with ACHD diagnosis codes were filtered between 2006-2011 from an all-payer inpatient healthcare database. Hospital-level data was linked to market structure patient flow. A common measure of market concentration used to determine market competitiveness-the Herfindahl-Hirschman Index (HHI)-was stratified into: more competitive (HHI ≤25th percentile), moderately competitive (HHI 25th to <75th percentile), and less competitive (HHI ≥75th percentile) hospital. Any complication, home discharge and mortality were analyzed with clustered mixed effects logistic regression. The combined impact of HHI and any complication on mortality by interaction was assessed. RESULTS: A total of 67,434 patient discharges were isolated. More competitive hospitals discharged the least number of patients (N = 15,270, 22.6%) versus moderately competitive (N = 36,244, 53.7%) and less competitive (N = 15,920, 23.6%) hospitals. The adjusted odds of any complication or home discharge were not associated with hospital competitiveness strata. Compared to more competitive hospitals, mortality at moderately competitive hospitals (Adjusted Odds Ratio (AOR) 0.79, 95% CI: 0.66-0.94) and less competitive hospitals (AOR 0.79, 95% CI: 0.63-0.98) were lower (p = 0.025). Age, race, elective admission, transfer status, and payer mix were all significantly associated with adjusted odds of any complication, home discharge and mortality (p ≤ 0.05). Having any complication independently increased the adjusted odds of mortality more than 6-fold (p < 0.001), and this trend was independent of HHI strata. Failure to rescue an ACHD patient from mortality after having any complication is highest at less competitive hospitals. Sensitivity analysis which excluded the transfer status variable, showed that any complication (p = 0.047) and mortality (p = 0.01) were independently associated with HHI strata. CONCLUSIONS: Whether lower competition allow hospitals to focus more on quality of care is unknown. Hospital competitiveness and outcome seem to have an inverse trend relationship among ACHD patients. Since medical care is frequently provided away from the home area, hospital selection is an important issue for ACHD patients. Further research is needed to determine why competitiveness is linked to surgical outcomes in this population.

Gamma' fibrinogen levels as a biomarker of COVID-19 respiratory disease severity.

Coronavirus disease 2019 (COVID-19) is characterized by a pro-inflammatory state associated with organ failure, thrombosis, and death. We investigated a novel inflammatory biomarker, γ' fibrinogen (GPF), in 103 hospitalized patients with COVID-19 and 19 healthy controls. We found significant associations between GPF levels and the severity of COVID-19 as judged by blood oxygen saturation (SpO 2 ). The mean level of GPF in the patients with COVID-19 was significantly higher than in controls (69.8 (95% CI 64.8-74.8) mg/dL compared with 36.9 (95% CI 31.4-42.4) mg/dL, p < 0.0001), whereas C-reactive protein (CRP), lactate dehydrogenase (LDH), and total fibrinogen levels were not significantly different between groups. Mean GPF levels were significantly highest in patients with severe COVID-19 (SpO 2 ≤ 93%, GPF 75.2 (95% CI 68.7-81.8) mg/dL), compared to mild/moderate COVID-19 (SpO 2 > 93%, GPF 62.5 (95% CI 55.0-70.0) mg/dL, p = 0.01, AUC of 0.68, 95% CI 0.57-0.78; Youden's index cutpoint 62.9 mg/dL, sensitivity 0.64, specificity 0.63). In contrast, CRP, interleukin-6, ferritin, LDH, D-dimers, and total fibrinogen had weaker associations with COVID-19 disease severity (all ROC curves with lower AUCs). Thus, GPF may be a useful inflammatory marker of COVID-19 respiratory disease severity.