New occurrences of the bone-eating worm Osedax from Late Cretaceous marine reptiles and implications for its biogeography and diversification.

The bone-eating worm Osedax is a speciose and globally distributed clade, primarily found on whale carcasses in marine environments. The earliest fossil evidence for Osedax borings was previously described in plesiosaur and sea turtle bones from the mid-Cretaceous of the United Kingdom, representing the only unequivocal pre-Oligocene occurrences. Confirming through CT scanning, we present new evidence of Osedax borings in three plesiosaur specimens and, for the first time, identify borings in two mosasaur specimens. All specimens are from the Late Cretaceous: one from the Cenomanian of the United Kingdom, two from the Campanian of the southeastern United States, and two from the Maastrichtian of Belgium. This extends the geographic range of Osedax in the Cretaceous to both sides of the northern Atlantic Ocean. The bones contain five borehole morphotypes, potentially created by different species of Osedax, with the Cenomanian specimen containing three morphotypes within a single tooth. This combined evidence of heightened species diversity by the Cenomanian and broad geographic range by the Campanian potentially indicates an earlier origin and diversification for this clade than previously hypothesized. Preservational biases indicate that Osedax was probably even more widely distributed and speciose in the Cretaceous than apparent in the fossil record.

Dietary niche partitioning in Early Jurassic ichthyosaurs from Strawberry Bank.

Jurassic ichthyosaurs dominated upper trophic levels of marine ecosystems. Many species coexisted alongside each another, and it is uncertain whether they competed for the same array of food or divided dietary resources, each specializing in different kinds of prey. Here, we test whether feeding differences existed between species, applying finite element analysis to ichthyosaurs for the first time. We examine two juvenile ichthyosaur specimens, referred to Hauffiopteryx typicus and Stenopterygius triscissus, from the Strawberry Bank Lagerstätte, a shallow marine environment from the Early Jurassic of southern England (Toarcian, ~183 Ma). Snout and cranial robusticity differ between the species, with S. triscissus having a more robust snout and cranium and specializing in slow biting of hard prey, and H. typicus with its slender snout specializing in fast, but weaker bites on fast-moving, but soft prey. The two species did not differ in muscle forces, but stress distributions varied in the nasal area, reflecting differences when biting at different points along the tooth row: the more robustly snouted Stenopterygius resisted increases or shifts in stress distribution when the bite point was shifted from the posterior to the mid-point of the tooth row, but the slender-snouted Hauffiopteryx showed shifts and increases in stress distributions between these two bite points. The differences in cranial morphology, dentition and inferred stresses between the two species suggest adaptations for dietary niche partitioning.

Kidney thrombotic microangiopathy in lupus nephritis: Impact on treatment and prognosis.

INTRODUCTION: Lupus nephritis (LN) may present with thrombotic microangiopathy (TMA) on kidney biopsy, the impact of which on outcomes is unclear. This study examined the prognostic importance of LN with TMA on kidney biopsy, including response to therapy and long-term outcomes. METHODS: We conducted a single-center, retrospective study of all cases of LN with concomitant TMA on kidney biopsy in the Glomerular Disease Collaborative Network database. Controls were individuals with LN without TMA matched to cases based on demographic and clinical variables. Outcomes were remission at 6- and 12-months, end-stage kidney disease (ESKD) and death. Logistic regression and Cox proportional hazards models were used to ascertain the risks for outcomes, with adjustment for serum creatinine and proteinuria. RESULTS: There were 17 cases and 28 controls. Cases had higher creatinine, higher proteinuria and greater chronicity on biopsy at baseline compared to controls. The rates of remission at 6-months and 12-months were similar between cases and controls (6-months 53.9% vs 46.4%, adjusted OR 2.54, 95% CI 0.48, 13.37; 12-months 53.9% vs 50.0%, adjusted OR 2.95, 95% CI 0.44, 19.78). Cases were at greater risk for ESKD in univariate analysis (HR 3.77; 95% CI 1.24, 11.41) but not when adjusting for serum creatinine and proteinuria (HR 2.20; 95% CI 0.63, 7.71). There was no significant difference in the risk of death between cases and controls. CONCLUSION: Lupus nephritis with renal TMA likely responds to therapy similarly to those without TMA; risk for ESKD is not significantly increased, although the influence of renal function and proteinuria in larger samples is needed.

Therapeutic plasma exchange in the intensive care unit and with the critically ill, a focus on clinical nursing considerations.

Therapeutic plasma exchange (TPE) is a blood purification technique removing antibodies and plasma proteins to modulate disease and promote recovery. The procedure has different methods, using a membrane or plasma separator with many elements similar to continuous renal replacement therapy (CCRT) in the Intensive Care Unit (ICU). These nursing knowledge and skill sets apply where ICU nurses are providing TPE with increasing need. However, different care models are also in place where TPE is the responsibility of apheresis and nephrology teams visiting the ICU. The plasma replacement volume and prescribing is aligned with published guidelines but is variable when critical illness overlays the primary indication for TPE. There are some important considerations for TPE with respect to anticoagulation, machine settings, prescribing, and associated nursing management. TPE can be performed concurrent with CRRT in acute situations using Y-piece and valve connectors and is a new and recent advanced blood purification for the ICU.

Impact of age, comorbidity, and treatment characteristics on survival in older women with advanced high grade epithelial ovarian cancer.

OBJECTIVES: Older women have a worse prognosis with advanced epithelial ovarian cancer (EOC) and comorbidities likely contribute to poor outcomes. We sought to identify comorbid conditions and treatment-related factors in older women. METHODS: A retrospective chart review identified 351 patients who underwent cytoreductive surgery (CRS). 100/351 (28.5%) were ≥ 70 years old. Demographic and clinicopathologic information was collected. Crude progression-free (PFS) and overall survival (OS) estimates were calculated using Kaplan-Meier method. Cox proportional hazards regression model was used to estimate hazard ratios and adjustments for confounders. RESULTS: Study subjects ≥70 years old had significantly: higher Cumulative Illness Rating Scale-Geriatric (CIRS-G) score (5.9 vs 4.3; p = 0.0001), less completion of adjuvant chemotherapy (24% vs 15.1%; p = 0.049), less intraperitoneal (IP) therapy (18.2% vs 35.5%; p = 0.002), less clinical trial participation (16% vs 26.3%; p = 0.040), decreased platinum sensitivity (60% vs 73.7%; p = 0.012) and lacked BRCA mutations (0% vs 12%; p = 0.0006). They were less likely to have optimal CRS (75% vs 86.9%; p = 0.007) with same surgical complexity (p = 0.89). Patients ≥70 had significantly worse PFS and OS. In a multivariate analysis, better OS was associated with younger age (<70 years old), any IP therapy, completion of adjuvant chemotherapy, and platinum sensitivity. CONCLUSION: The older cohort had worse CIRS-G scores (5.9 vs 4.3; p = 0.0001), but no strong associations between comorbidities and treatment characteristics, but less optimal CRS rates (75% vs 86.9%; p = 0.007) with similar surgical complexity and less platinum sensitivity. Our results show comorbid conditions in older patients with advanced EOC may have less impact than tumor biology.

Role of adjuvant chemotherapy in patients with FIGO stage IB grade 3 endometrial endometrioid adenocarcinoma treated with surgery and post-operative radiotherapy.

BACKGROUND: The optimal treatment of patients with FIGO stage IB grade 3 endometrial endometrioid adenocarcinoma remains unknown. OBJECTIVE: To compare overall survival following treatment with a hysterectomy and adjuvant radiotherapy with or without chemotherapy in this group of patients. METHODS: Patients diagnosed between January 2004 and January 2016 with FIGO stage IB grade 3 endometrial endometrioid adenocarcinoma treated with hysterectomy and postoperative radiotherapy with or without adjuvant concurrent chemotherapy were identified in the National Cancer Database. Overall survival was assessed with Kaplan-Meier curves. A Cox model was constructed to evaluate survival after controlling for confounding variables. A logistic regression model was used to reveal predictors of chemotherapy use. RESULTS: A total of 2173 patients were included. The receipt of chemotherapy was associated with an increased 5-year overall survival from 67.6% to 75.6% (p=0.0313). This association trended toward statistical significance on multivariate analysis (adjusted HR (aHR) 0.80; 95% CI 0.63 to 1.01; p=0.0653). Other factors associated with improved survival were undergoing a lymphadenectomy, absence of lymphovascular space invasion, younger age, smaller tumor size, non-black race, and absence of comorbidities. Patients who underwent brachytherapy, had lymphovascular space invasion, were younger, were diagnosed in the more recent years, and were treated in higher volume centers were more likely to receive adjuvant chemotherapy. CONCLUSION: Adjuvant chemotherapy and radiation therapy were associated with an increase in survival in patients with FIGO stage IB grade 3 endometrial endometrioid adenocarcinoma compared with those treated with adjuvant radiotherapy alone.

Topical rapamycin for acanthosis nigricans in the Fitzpatrick IV/V adolescent population.

Dermatologically, FGFR3 mutations can lead to acanthosis nigricans (AN), epidermal nevi, and seborrheic keratosis. A recent case report found that topical rapamycin (sirolimus) can improve FGFR3-induced epidermal nevi with AN features in children, specifically with Fitzpatrick skin type (FST) I/II, and we would like to expand these findings to skin plaques with extensive AN-like features in the FST IV/V adolescent population. An 18-year-old female with FST IV/V and FGFR3-induced hypochondroplasia presented to our clinic with extensive AN-like plaques. Significant improvement with lightening and thinning of the plaques was observed after applying 1% topical rapamycin cream twice daily. Topical rapamycin should be considered as a treatment option for AN, particularly in FST IV/V adolescents with FGFR3-induced AN.

Trends in Incidence and Mortality Rates of Uterine Cancer in Kentucky.

OBJECTIVES: The objective of this analysis was to gauge how the incidence and mortality of uterine cancer in Kentucky have changed from 1995 through 2017. An assessment of the trends in incidence and mortality across different geographic areas and between different races was also performed. METHODS: Age-adjusted annual incidence and mortality rates for uterine cancer were obtained from the Kentucky Cancer Registry. A meta-regression framework was used to assess changes in incidence and mortality rates during the time frame and to determine differences in these rates between rural versus urban counties, Appalachian versus non-Appalachian counties, and Black versus White women. RESULTS: The incidence of uterine cancer has significantly increased throughout the state of Kentucky since 1995. Uterine cancer incidence was 10% and 22% higher in rural and Appalachian counties, respectively, compared with urban and non-Appalachian counties (P < 0.0001) from 1995 through 2017. In contrast, urban and non-Appalachian women had higher or equivalent age-adjusted mortality from uterine cancer, compared with rural and Appalachian women, respectively. The incidence of uterine cancer was significantly higher in White women compared with Black women from 1995 through 2006, but since 2007, there has been no significant difference in uterine cancer incidence based on race. Black women had higher age-adjusted mortality than White women throughout the entire time period examined. CONCLUSIONS: The incidence of uterine cancer is higher in rural and Appalachian Kentucky, without a corresponding geographic trend in mortality. Uterine cancer mortality is significantly higher in Black women.

Retrospective Review for Medication Dose Errors in Pediatric Emergency Department Medication Orders That Bypassed Pharmacist Review.

OBJECTIVE: To identify and evaluate dose errors on medication orders that bypassed pharmacist verification in a pediatric emergency department (PED). METHODS: Descriptive, retrospective study about dose errors in an academic PED over 1 year. A report of automatically verified orders (those that bypassed pharmacist verification) was obtained from the electronic medical record. Potential medication dose errors were defined as those greater than 20% above or below standard dose ranges by age or weight. A retrospective chart review was performed for all identified dose errors. For orders deemed erroneous, additional metrics collected included order time of day and day of week and provider training level. RESULTS: A total of 46,185 medication orders were placed; 32,928 (71%) bypassed pharmacist review. Altogether, 676 orders (2%) were outside standard dose ranges. Ondansetron represented 569 of the 676 orders; most were doses rounded down to 4 mg and technically qualifying as underdoses, but were attributed to practice variance and not further analyzed. The number of orders deemed potentially erroneous was 107: most were wrong dose (75 overdose and 21 underdose), 5 were wrong patient, and 6 were wrong formulation. Ibuprofen, benzodiazepine, and corticosteroid orders had the most errors. No errors resulted in identifiable harm to the patient: 49 were near misses, and 47 reached the patient with no evident harm. CONCLUSIONS: The overall number of dose errors in autoverified orders was low. Certain medications or ordering modalities may be targeted to enhance patient safety and satisfaction.

Patterns and predictors of genetic referral among ovarian cancer patients at a National Cancer Institute-Comprehensive Cancer Center.

Germline mutations (eg, BRCA1/2) have prognostic and treatment implications for ovarian cancer (OVCA) patients. Thus, national guidelines recommend genetic testing for OVCA patients. The present study examines patterns and predictors of genetics referral in OVCA patients. Electronic medical record data were abstracted retrospectively from 557 OVCA patients treated from 1 January 2001 to 31 December 2015. Logistic regression models identified sociodemographic characteristics, disease/treatment characteristics, family history data, provider characteristics, and survival data that predicted genetics referral. Overall, 27.5% of patients received referral. Eleven variables predicting referral were selected during stepwise regression: younger age, White race, not having private insurance, professional school education, year of OVCA diagnosis, platinum sensitivity, female gynecologic oncologist, chemotherapy administered by a gynecologic oncologist, clinical trial enrollment, longer overall survival, and family history of OVCA. Genetics referral among OVCA patients was similar to rates reported nationwide. Unique predictive factors will contribute to quality improvement and should be validated at a multi-institutional level to ensure guideline concordant care is provided to all OVCA patients. Future research should identify both patient-level and provider-level factors associated with genetics referral.

Cervical cancer incidence and mortality rates in Kentucky.

OBJECTIVES: The goal of this study was to assess how the incidence and mortality of cervical cancer in Kentucky has changed from 1995 through 2017. Additionally, trends in incidence and mortality across different geographic areas and between different races were evaluated. METHODS: Age-adjusted annual incidence and mortality rates for cervical cancer were collected from the Kentucky Cancer Registry (KCR). A quadratic fit model was used to evaluate changes in the incidence and mortality over time and to compare differences in cervical cancer incidence and mortality by: 1) rural versus urban counties, 2) Appalachian versus non-Appalachian counties, and 3) black versus white women. RESULTS: Overall, the incidence of cervical cancer has significantly decreased throughout Kentucky since 1995. When comparing different geographic regions, the incidence was 14% and 23% higher in rural and Appalachian counties, respectively, compared to urban and non-Appalachian counties (p < 0.0001) throughout the study period. The incidence of cervical cancer was significantly higher in black women compared to white women from 1995 through 2007, but since 2008 there has been no significant difference in cervical cancer incidence based on race. Similar to incidence rates, mortality from cervical cancer was 29% higher in Appalachia (p = 0.0004) throughout the studied time period. Black women had higher age-adjusted mortality than white women until 2012, but since that time there has not been a significant difference in cervical cancer mortality based on race. CONCLUSIONS: Women residing in rural and Appalachian Kentucky have higher cervical cancer incidence and mortality rates.

Dual antibiotic prevention bundle is associated with decreased surgical site infections.

BACKGROUND: Gynecologic oncology surgery is associated with a wide variation in surgical site infection risk. The optimal method for infection prevention in this heterogeneous population remains uncertain. STUDY DESIGN: A retrospective cohort study was performed to compare surgical site infection rates for patients undergoing hysterectomy over a 1-year period surrounding the implementation of an institutional infection prevention bundle. The bundle comprised pre-operative, intra-operative, and post-operative interventions including a dual-agent antibiotic surgical prophylaxis with cefazolin and metronidazole. Cohorts consisted of patients undergoing surgery during the 6 months prior to this intervention (pre-bundle) versus those undergoing surgery during the 6 months following the intervention (post-bundle). Secondary outcomes included length of stay, readmission rates, compliance measures, and infection microbiology. Data were compared with pre-specified one-sided exact test, Chi-square test, Fisher's exact test, or Kruskal-Wallis test as appropriate. RESULTS: A total of 358 patients were included (178 PRE, 180 POST). Median age was 58 (range 23-90) years. The post-bundle cohort had a 58% reduction in surgical site infection rate, 3.3% POST vs 7.9% PRE (-4.5%, 95% CI -9.3% to -0.2%, p=0.049) as well as reductions in organ space infection, 0.6% POST vs 4.5% PRE (-3.9%, 95% CI -7.2% to -0.7%, p=0.019), and readmission rates, 2.2% POST vs 6.7% PRE (-4.5%, 95% CI -8.7% to -0.2%, p=0.04). Gram-positive, Gram-negative, and anaerobic bacteria were all prevalent in surgical site infection cultures. There were no monomicrobial infections in post-cohort cultures (0% POST vs 58% PRE, p=0.04). No infections contained methicillin-resistant Staphylococcus aureus. CONCLUSION: Implementation of a dual antibiotic infection prevention bundle was associated with a 58% reduction in surgical site infection rate after hysterectomy in a surgically diverse gynecologic oncology practice.

Patient and public involvement facilitators: Could they be the key to the NHS quality improvement agenda?

OBJECTIVE: Research into patient and public involvement (PPI) has not examined in detail patient and public involvement facilitators' (PPIFs) roles and activities. This study analysed PPIFs' roles using qualitative data gathered from three different UK health-care organizations. DESIGN: Thematic analysis was used to examine cross-sectional data collected using a mixed-methods approach from three organizations: a mental health trust, a community health social enterprise and an acute hospital trust. The data set comprised of 27 interviews and 48 observations. FINDINGS: Patient and public involvement facilitators roles included the leadership and management of PPI interventions, developing health-care practices and influencing quality improvements (QI). They usually occupied middle-management grades but their PPIF role involved working in isolation or in small teams. They reported facilitating the development and maintenance of relationships between patients and the public, and health-care professionals and service managers. These roles sometimes required them to use conflict resolution skills and involved considerable emotional labour. Integrating information from PPI into service improvement processes was reported to be a challenge for these individuals. CONCLUSIONS: Patient and public involvement facilitators capture and hold information that can be used in service improvement. However, they work with limited resources and support. Health-care organizations need to offer more practical support to PPIFs in their efforts to improve care quality, particularly by making their role integral to developing QI strategies.

Novel assessment tool to detect breathing pattern disorder in patients with refractory asthma.

BACKGROUND AND OBJECTIVE: Breathing pattern disorder (BPD) can co-exist with and mimic asthma, acting to amplify symptoms and confound assessment of disease control, resulting in inappropriate treatment escalation. The aim of this research was to report the utility of a novel breathing pattern assessment tool (BPAT) to detect BPD in treatment-refractory asthma. METHODS: As a component of a multidisciplinary assessment, adult patients referred with treatment-refractory asthma underwent respiratory physiotherapy assessment to diagnose BPD. Based on this assessment, patients were classified as having asthma, asthma + BPD or BPD alone. BPAT data were collected in addition to questionnaire data (Asthma Quality of Life Questionnaire (AQLQ) and Nijmegen Questionnaire (NQ)), pulmonary function and an assessment of exercise capacity. RESULTS: Data were retrospectively analysed for 150 (female; 69%) patients, mean (SD) age of 43 (14) years; characterized as asthma-only (n = 54, 36%), asthma + BPD (n = 63, 42%) and BPD-only (n = 33, 22%). Of the total population, 113 (76%) had an NQ score ≥23, but of these only 68% had physiotherapy evidence of BPD. Exercise capacity and AQLQ were lower in the asthma + BPD group than in the asthma-only group (P < 0.05), whilst lung function was similar between groups. Sensitivity analysis indicated that a BPAT score of ≥4 corresponded to a sensitivity of 0.92 and a specificity of 0.75 for diagnosis of BPD in this cohort. CONCLUSION: Breathing pattern irregularities are highly prevalent in individuals referred with treatment-refractory asthma and can be characterized using the BPAT. Further work is needed to determine inter-observer and within-subject variability and ensure the BPAT is a robust clinical tool. Watch the video abstract.

Regulatory B cells are numerically but not functionally deficient in anti-neutrophil cytoplasm antibody-associated vasculitis.

OBJECTIVES: B cells are central to the pathology of ANCA-associated vasculitis (AAV), a disease characterized by autoantibodies and effectively treated by rituximab. In addition to promoting inflammation, a subset of B cells act to suppress harmful autoimmune responses (Breg). The balance of effector and regulatory B cell subsets in AAV is not known. This study was conducted to assess the relative frequency of these subsets during different states of disease activity. METHODS: B memory (Bmem), naive (Bnaive) and regulatory (Breg) subsets were defined by their relative expression of CD24 and CD38. Function was assessed by cytokine production and suppressive action on CD4(+) Th1 activation evaluated in a co-culture system. RESULTS: Compared with healthy controls, the frequency of Breg (CD24(hi)CD38(hi)) was significantly reduced during disease remission in both proteinase 3 (PR3)- and MPO-ANCA patients and during acute disease in PR3-ANCA patients, while the frequency of memory cells (CD24(hi)CD38(lo)) was reduced during active disease and restored during remission. Breg cell frequency showed a positive correlation, while Bmem had an inverse correlation with IL-10 production in vitro. B and T cell co-cultures revealed that memory and naive B cell subsets augmented Th1 activation in vitro, which was prevented by Breg, and this pattern did not differ between remission AAV patients and controls. CONCLUSION: In remission there is a numerical, but not functional, deficiency in Breg and preservation of Bmem associated with reduced IL-10 production and increased Th1 activation in vitro. This imbalance may contribute to the high rate of relapse observed in AAV, especially in PR3-ANCA patients.

Expression of functional P-selectin glycoprotein ligand 1 on hematopoietic progenitors is developmentally regulated.

T cell development requires periodic importation of hematopoietic progenitors into the thymus. The receptor-ligand pair P-selectin and P-selectin glycoprotein ligand 1 (PSGL-1) are critically involved in this process. In this study, we examined the expression of functional PSGL-1 on bone marrow hematopoietic progenitors. We demonstrate that functional PSGL-1 is expressed at low levels on hematopoietic stem cells, but upregulated on the cell surface of progenitors that bear other homing molecules known to be important for thymic settling. We found that progenitors able to home to the thymus expressed high levels of PSGL-1 transcripts compared with hematopoietic stem cells. We further demonstrate that hematopoietic progenitors lacking fucosyltransferase 4 and 7 do not express functional PSGL-1, and do not home efficiently to the thymus. These studies provide insight into the developmentally regulated expression of a critical determinant involved in progenitor homing to the thymus.

Surface architecture of endospores of the Bacillus cereus/anthracis/thuringiensis family at the subnanometer scale.

Bacteria of the Bacillus cereus family form highly resistant spores, which in the case of the pathogen B. anthracis act as the agents of infection. The outermost layer, the exosporium, enveloping spores of the B. cereus family as well as a number of Clostridia, plays roles in spore adhesion, dissemination, targeting, and germination control. We have analyzed two naturally crystalline layers associated with the exosporium, one representing the "basal" layer to which the outermost spore layer ("hairy nap") is attached, and the other likely representing a subsurface ("parasporal") layer. We have used electron cryomicroscopy at a resolution of 0.8-0.6 nm and circular dichroism spectroscopic measurements to reveal a highly α-helical structure for both layers. The helices are assembled into 2D arrays of "cups" or "crowns." High-resolution atomic force microscopy of the outermost layer showed that the open ends of these cups face the external environment and the highly immunogenic collagen-like fibrils of the hairy nap (BclA) are attached to this surface. Based on our findings, we present a molecular model for the spore surface and propose how this surface can act as a semipermeable barrier and a matrix for binding of molecules involved in defense, germination control, and other interactions of the spore with the environment.

The Feasibility and Acceptability of a Diabetes Survival Skills Intervention for Persons Transitioning from Prison to the Community.

Community evidenced-based diabetes self-management education (DSME) models have not been examined for feasibility, acceptability, or effectiveness among persons transitioning from prison to the community to independent diabetes self-management (DSM). In a non-equivalent control group design with repeated measures, we examined the feasibility, acceptability, and preliminary effect of a 6-week, 1-h per week Diabetes Survival Skills (DSS) intervention on diabetes knowledge, distress, self-efficacy, and outcome expectancy for transitioning incarcerated males. Of the 92 participants (84% T2D, 83% using insulin, 40% Black, 20% White, 30% Latino, 66% high school or less, mean age 47.3 years, 84% length of incarceration ≤4 years ), 41 completed the study (22 control/19 intervention [TX]). One-way repeated measures ANOVAs revealed significant changes in diabetes knowledge within each group (C, p = .002; TX, p = .027) at all time points; however, a two-way repeated measures ANOVA showed no differences between groups. Additionally, both groups showed improvement in diabetes-related distress and outcome expectancy with the treatment group experiencing greater and sustained improvement at the 12-week time point. Analysis of focus group data (Krippendorf) revealed acceptance of and enthusiasm for the DSS training and low literacy education materials, the need for skill demonstration, and ongoing support throughout incarceration and before release. Our results highlight the complexity of working with incarcerated populations. After most of the sessions, we observed some information sharing between the intervention and the control groups on what they did in their respective sessions. Due to high attrition, the power to detect effects was limited. Yet, results suggest that the intervention is feasible and acceptable with an increased sample size and refined recruitment procedure. NCT05510531, 8/19/2022, retrospectively, registered.

Leukocyte and serum S100A8/S100A9 expression reflects disease activity in ANCA-associated vasculitis and glomerulonephritis.

Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) commonly results in glomerulonephritis, in which neutrophils and monocytes have important roles. The heterodimer calprotectin (S100A8/S100A9, mrp8/14) is a Toll-like receptor-4 ligand found in neutrophils and monocytes and is elevated in inflammatory conditions. By immunohistochemistry of renal biopsies, patients with focal or crescentic glomerular lesions were found to have the highest expression of calprotectin and those with sclerotic the least. Serum levels of calprotectin as measured by ELISA were elevated in patients with active AAV and the levels decreased but did not normalize during remission, suggesting subclinical inflammation. Calprotectin levels in patients with limited systemic disease increased following treatment withdrawal and were significantly elevated in patients who relapsed compared with those who did not. As assessed by flow cytometry, patients with AAV had higher monocyte and neutrophil cell surface calprotectin expression than healthy controls, but this was not associated with augmented mRNA expression in CD14(+) monocytes or CD16(+) neutrophils. Thus, serum calprotectin is a potential disease biomarker in patients with AAV, and may have a role in disease pathogenesis.