Survivors of polymicrobial sepsis are refractory to G-CSF-induced emergency myelopoiesis and hematopoietic stem and progenitor cell mobilization.

Sepsis survivors exhibit immune dysfunction, hematological changes, and increased risk of infection. The long-term impacts of sepsis on hematopoiesis were analyzed using a surgical model of murine sepsis, resulting in 50% survival. During acute disease, phenotypic hematopoietic stem and progenitor cells (HSPCs) were reduced in the bone marrow (BM), concomitant with increased myeloid colony-forming units and extramedullary hematopoiesis. Upon recovery, BM HSPCs were increased and exhibited normal function in the context of transplantation. To evaluate hematopoietic responses in sepsis survivors, we treated recovered sham and cecal ligation and puncture mice with a mobilizing regimen of granulocyte colony-stimulating factor (G-CSF) at day 20 post-surgery. Sepsis survivors failed to undergo emergency myelopoiesis and HSPC mobilization in response to G-CSF administration. G-CSF is produced in response to acute infection and injury to expedite the production of innate immune cells; therefore, our findings contribute to a new understanding of how sepsis predisposes to subsequent infection.

Vaccine effectiveness against influenza hospitalisation in adults during the 2022/2023 mixed season of influenza A(H1N1)pdm09, A(H3N2) and B circulation, Europe: VEBIS SARI VE hospital network.

We conducted a multicentre hospital-based test-negative case-control study to measure vaccine effectiveness (VE) against PCR-confirmed influenza in adult patients with severe acute respiratory infection (SARI) during the 2022/2023 influenza season in Europe. Among 5547 SARI patients ≥18 years, 2963 (53%) were vaccinated against influenza. Overall VE against influenza A(H1N1)pdm09 was 11% (95% CI: -23-36); 20% (95% CI: -4-39) against A(H3N2) and 56% (95% CI: 22-75) against B. During the 2022/2023 season, while VE against hospitalisation with influenza B was >55%, it was ≤20% for influenza A subtypes. While influenza vaccination should be a priority for future seasons, improved vaccines against influenza are needed.

Interim 2023/24 influenza A vaccine effectiveness: VEBIS European primary care and hospital multicentre studies, September 2023 to January 2024.

Influenza A viruses circulated in Europe from September 2023 to January 2024, with influenza A(H1N1)pdm09 predominance. We provide interim 2023/24 influenza vaccine effectiveness (IVE) estimates from two European studies, covering 10 countries across primary care (EU-PC) and hospital (EU-H) settings. Interim IVE was higher against A(H1N1)pdm09 than A(H3N2): EU-PC influenza A(H1N1)pdm09 IVE was 53% (95% CI: 41 to 63) and 30% (95% CI: -3 to 54) against influenza A(H3N2). For EU-H, these were 44% (95% CI: 30 to 55) and 14% (95% CI: -32 to 43), respectively.

Carbon removal and climate change mitigation by seaweed farming: A state of knowledge review.

The pressing need to mitigate the effects of climate change is driving the development of novel approaches for carbon dioxide removal (CDR) from the atmosphere, with the ocean playing a central role in the portfolio of solutions. The expansion of seaweed farming is increasingly considered as one of the potential CDR avenues among government and private sectors. Yet, comprehensive assessments examining whether farming can lead to tangible climate change mitigation remain limited. Here we examine the results of over 100 publications to synthesize evidence regarding the CDR capacity of seaweed farms and review the different interventions through which an expansion of seaweed farming may contribute to climate change mitigation. We find that presently, the majority of the carbon fixed by seaweeds is stored in short-term carbon reservoirs (e.g., seaweed products) and that only a minority of the carbon ends up in long-term reservoirs that are likely to fit within existing international accounting frameworks (e.g., marine sediments). Additionally, the tiny global area cultivated to date (0.06 % of the estimated wild seaweed extent) limits the global role of seaweed farming in climate change mitigation in the present and mid-term future. A first-order estimate using the best available data suggests that, at present, even in a low emissions scenario, any carbon removal capacity provided by seaweed farms globally is likely to be offset by their emissions (median global balance net emitter: -0.11 Tg C yr-1; range -2.07-1.95 Tg C yr-1), as most of a seaweed farms' energy and materials currently depend on fossil fuels. Enhancing any potential CDR though seaweed farming will thus require decarbonizing of supply chains, directing harvested biomass to long-term carbon storage products, expanding farming outside traditional cultivation areas, and developing robust models tracing the fate of seaweed carbon. This will present novel scientific (e.g., verifying permanence of seaweed carbon), engineering (e.g., developing farms in wave exposed areas), and economic challenges (e.g., increase market demand, lower costs, decarbonize at scale), many of which are only beginning to be addressed.

Effectiveness of the adapted bivalent mRNA COVID-19 vaccines against hospitalisation in individuals aged ≥ 60 years during the Omicron XBB lineage-predominant period: VEBIS SARI VE network, Europe, February to August, 2023.

We conducted a multicentre hospital-based test-negative case-control study to measure the effectiveness of adapted bivalent COVID-19 mRNA vaccines against PCR-confirmed SARS-CoV-2 infection during the Omicron XBB lineage-predominant period in patients aged ≥ 60 years with severe acute respiratory infection from five countries in Europe. Bivalent vaccines provided short-term additional protection compared with those vaccinated > 6 months before the campaign: from 80% (95% CI: 50 to 94) for 14-89 days post-vaccination, 15% (95% CI: -12 to 35) at 90-179 days, and lower to no effect thereafter.

Vaccine effectiveness against COVID-19 hospitalisation in adults (≥ 20 years) during Alpha- and Delta-dominant circulation: I-MOVE-COVID-19 and VEBIS SARI VE networks, Europe, 2021.

IntroductionTwo large multicentre European hospital networks have estimated vaccine effectiveness (VE) against COVID-19 since 2021.AimWe aimed to measure VE against PCR-confirmed SARS-CoV-2 in hospitalised severe acute respiratory illness (SARI) patients ≥ 20 years, combining data from these networks during Alpha (March-June)- and Delta (June-December)-dominant periods, 2021.MethodsForty-six participating hospitals across 14 countries follow a similar generic protocol using the test-negative case-control design. We defined complete primary series vaccination (PSV) as two doses of a two-dose or one of a single-dose vaccine ≥ 14 days before onset.ResultsWe included 1,087 cases (538 controls) and 1,669 cases (1,442 controls) in the Alpha- and Delta-dominant periods, respectively. During the Alpha period, VE against hospitalisation with SARS-CoV2 for complete Comirnaty PSV was 85% (95% CI: 69-92) overall and 75% (95% CI: 42-90) in those aged ≥ 80 years. During the Delta period, among SARI patients ≥ 20 years with symptom onset ≥ 150 days from last PSV dose, VE for complete Comirnaty PSV was 54% (95% CI: 18-74). Among those receiving Comirnaty PSV and mRNA booster (any product) ≥ 150 days after last PSV dose, VE was 91% (95% CI: 57-98). In time-since-vaccination analysis, complete all-product PSV VE was > 90% in those with their last dose < 90 days before onset; ≥ 70% in those 90-179 days before onset.ConclusionsOur results from this EU multi-country hospital setting showed that VE for complete PSV alone was higher in the Alpha- than the Delta-dominant period, and addition of a first booster dose during the latter period increased VE to over 90%.

Vaccine effectiveness against COVID-19 hospitalisation in adults (≥ 20 years) during Omicron-dominant circulation: I-MOVE-COVID-19 and VEBIS SARI VE networks, Europe, 2021 to 2022.

IntroductionThe I-MOVE-COVID-19 and VEBIS hospital networks have been measuring COVID-19 vaccine effectiveness (VE) in participating European countries since early 2021.AimWe aimed to measure VE against PCR-confirmed SARS-CoV-2 in patients ≥ 20 years hospitalised with severe acute respiratory infection (SARI) from December 2021 to July 2022 (Omicron-dominant period).MethodsIn both networks, 46 hospitals (13 countries) follow a similar test-negative case-control protocol. We defined complete primary series vaccination (PSV) and first booster dose vaccination as last dose of either vaccine received ≥ 14 days before symptom onset (stratifying first booster into received < 150 and ≥ 150 days after last PSV dose). We measured VE overall, by vaccine category/product, age group and time since first mRNA booster dose, adjusting by site as a fixed effect, and by swab date, age, sex, and presence/absence of at least one commonly collected chronic condition.ResultsWe included 2,779 cases and 2,362 controls. The VE of all vaccine products combined against hospitalisation for laboratory-confirmed SARS-CoV-2 was 43% (95% CI: 29-54) for complete PSV (with last dose received ≥ 150 days before onset), while it was 59% (95% CI: 51-66) after addition of one booster dose. The VE was 85% (95% CI: 78-89), 70% (95% CI: 61-77) and 36% (95% CI: 17-51) for those with onset 14-59 days, 60-119 days and 120-179 days after booster vaccination, respectively.ConclusionsOur results suggest that, during the Omicron period, observed VE against SARI hospitalisation improved with first mRNA booster dose, particularly for those having symptom onset < 120 days after first booster dose.

Carbon sequestration and climate change mitigation using macroalgae: a state of knowledge review.

The conservation, restoration, and improved management of terrestrial forests significantly contributes to mitigate climate change and its impacts, as well as providing numerous co-benefits. The pressing need to reduce emissions and increase carbon removal from the atmosphere is now also leading to the development of natural climate solutions in the ocean. Interest in the carbon sequestration potential of underwater macroalgal forests is growing rapidly among policy, conservation, and corporate sectors. Yet, our understanding of whether carbon sequestration from macroalgal forests can lead to tangible climate change mitigation remains severely limited, hampering their inclusion in international policy or carbon finance frameworks. Here, we examine the results of over 180 publications to synthesise evidence regarding macroalgal forest carbon sequestration potential. We show that research efforts on macroalgae carbon sequestration are heavily skewed towards particulate organic carbon (POC) pathways (77% of data publications), and that carbon fixation is the most studied flux (55%). Fluxes leading directly to carbon sequestration (e.g. carbon export or burial in marine sediments) remain poorly resolved, likely hindering regional or country-level assessments of carbon sequestration potential, which are only available from 17 of the 150 countries where macroalgal forests occur. To solve this issue, we present a framework to categorize coastlines according to their carbon sequestration potential. Finally, we review the multiple avenues through which this sequestration can translate into climate change mitigation capacity, which largely depends on whether management interventions can increase carbon removal above a natural baseline or avoid further carbon emissions. We find that conservation, restoration and afforestation interventions on macroalgal forests can potentially lead to carbon removal in the order of 10's of Tg C globally. Although this is lower than current estimates of natural sequestration value of all macroalgal habitats (61-268 Tg C year-1 ), it suggests that macroalgal forests could add to the total mitigation potential of coastal blue carbon ecosystems, and offer valuable mitigation opportunities in polar and temperate areas where blue carbon mitigation is currently low. Operationalizing that potential will necessitate the development of models that reliably estimate the proportion of production sequestered, improvements in macroalgae carbon fingerprinting techniques, and a rethinking of carbon accounting methodologies. The ocean provides major opportunities to mitigate and adapt to climate change, and the largest coastal vegetated habitat on Earth should not be ignored simply because it does not fit into existing frameworks.

Interim 2022/23 influenza vaccine effectiveness: six European studies, October 2022 to January 2023.

BackgroundBetween October 2022 and January 2023, influenza A(H1N1)pdm09, A(H3N2) and B/Victoria viruses circulated in Europe with different influenza (sub)types dominating in different areas.AimTo provide interim 2022/23 influenza vaccine effectiveness (VE) estimates from six European studies, covering 16 countries in primary care, emergency care and hospital inpatient settings.MethodsAll studies used the test-negative design, but with differences in other study characteristics, such as data sources, patient selection, case definitions and included age groups. Overall and influenza (sub)type-specific VE was estimated for each study using logistic regression adjusted for potential confounders.ResultsThere were 20,477 influenza cases recruited across the six studies, of which 16,589 (81%) were influenza A. Among all ages and settings, VE against influenza A ranged from 27 to 44%. Against A(H1N1)pdm09 (all ages and settings), VE point estimates ranged from 28% to 46%, higher among children (< 18 years) at 49-77%. Against A(H3N2), overall VE ranged from 2% to 44%, also higher among children (62-70%). Against influenza B/Victoria, overall and age-specific VE were ≥ 50% (87-95% among children < 18 years).ConclusionsInterim results from six European studies during the 2022/23 influenza season indicate a ≥ 27% and ≥ 50% reduction in disease occurrence among all-age influenza vaccine recipients for influenza A and B, respectively, with higher reductions among children. Genetic virus characterisation results and end-of-season VE estimates will contribute to greater understanding of differences in influenza (sub)type-specific results across studies.

Videofluoroscopic swallow study abnormalities identify aerodigestive disorders in dogs with respiratory disease versus healthy controls.

BACKGROUND: Aerodigestive diseases (AeroD) pathologically link respiratory and alimentary tracts. Dogs with respiratory signs lacking dysphagia, vomiting, or regurgitation typically do not undergo diagnostic testing that identifies comorbid alimentary disease. A videofluoroscopic swallow study (VFSS) identifies defects in swallowing, reflux, and aspiration. OBJECTIVES/HYPOTHESIS: We hypothesized that dogs with respiratory and no alimentary disease (RESP) would have significantly more abnormal VFSS metrics versus controls (CON). We hypothesized RESP dogs with pulmonary parenchymal disease would have more reflux and higher penetration-aspiration score (PAS) than those with airway disease. ANIMALS: Client-owned dogs: RESP (n = 45) and CON (n = 15) groups. METHODS: Prospectively, all dogs underwent VFSS. The RESP dogs had advanced respiratory diagnostic testing. Eight subjective and 3 objective VFSS metrics (pharyngeal constriction ratio [PCR], PAS, and esophageal transit time [ETT]) were assessed. Fisher's exact test compared differences between groups (presence or absence of VFSS abnormalities). The Mann-Whitney rank sum test was used to compare PCR and PAS. RESULTS: Subjective VFSS abnormalities were present in 34/45 (75%) RESP and 2/15 (13%) CON dogs, with RESP dogs significantly more likely to have VFSS abnormalities (P = .01). No difference in PCR was found between groups. Pathologic PAS was more common in RESP than CON dogs (P = .03). The RESP dogs with airway disease had higher PAS than CON dogs (P = .01) but not RESP dogs with parenchymal disease (P = .25). CONCLUSIONS: Most (75%) RESP dogs had VFSS abnormalities, emphasizing that AeroD are common. The VFSS has value in diagnostic evaluation of respiratory disease.

The effects of neuromuscular electrical stimulation to the ankle pronators on neural excitability & functional status in patients with chronic ankle instability.

OBJECTIVES: Chronic ankle instability (CAI) is associated with decreased neural excitability that negatively impacts function. This study assessed a 2-week neuromuscular electrical stimulation (NMES) or transcutaneous electrical nerve stimulation (TENS) intervention over the ankle pronators on neural excitability, performance, and patient-reported function in patients with CAI. STUDY DESIGN: Randomized controlled trial. PARTICIPANTS: Twenty participants with CAI completed the study. MAIN OUTCOME MEASURES: Participants were assessed for reflexive and corticospinal excitability to the ankle muscles, dynamic balance, side-hop test performance and patient-reported outcomes at baseline, post-intervention (2-weeks), and retention (4-weeks). Between baseline and post-intervention, participants reported for 5 sessions where they received either sub-noxious NMES (n = 11) or sensory-level TENS (n = 9) over the ankle pronators. RESULTS: Improved reflexive excitability to the ankle pronators was observed in TENS at post-intervention (p = 0.030) and retention (p = 0.029). Cortical excitability to the dorsiflexors increased in TENS at post-intervention (p = 0.017), but not at retention (p = 0.511). No significant changes were found for other neural measures, balance ability, hopping, or patient-reported function (p > 0.050). CONCLUSIONS: Our results suggest TENS modified neural excitability; however, these changes were not enough to impact clinical function. While TENS may be capable of neuromodulation, it may require rehabilitative exercise to generate lasting changes. NCT04322409. LEVEL OF EVIDENCE: Level 2.

Comparing the Primary Concerns of Injured Collegiate Athletes With the Content of Patient-Reported Outcome Measures.

CONTEXT: Patient-reported outcome measures (PROMs) have been endorsed for providing patient-centered care. However, PROMs must represent their target populations. OBJECTIVE: To identify the primary concerns of collegiate athletes experiencing injury and compare those with the content of established PROMs. DESIGN: Cross-sectional study. SETTING: Collegiate athletic training facilities. PATIENTS OR OTHER PARTICIPANTS: Collegiate athletes experiencing injury (N = 149). MAIN OUTCOME MEASURE(S): Open-ended responses to the Measure Yourself Medical Outcome Profile were used to identify primary concerns, which were linked to International Classification of Functioning, Disability and Health taxonomy codes. Items of the Patient-Reported Outcomes Measurement Information System; modified Disablement of the Physically Active Scale; Lower Extremity Functional Scale; Knee injury and Osteoarthritis Outcome Score (KOOS); International Knee Documentation Committee Subjective Knee Form (IKDC); Foot and Ankle Ability Measure; Disabilities of the Arm, Shoulder, and Hand; Functional Arm Scale for Throwers; and Kerlan-Jobe Orthopaedic Clinic questionnaire were linked to International Classification of Functioning, Disability and Health codes. We calculated χ2 single-sample goodness-of-fit tests to determine if 70% of the content was shared between PROMs and participant-generated codes. RESULTS: Participant-generated concerns were primarily related to sport participation (16%) and pain (23%). Chi-square tests showed that the Lower Extremity Functional Scale and Foot and Ankle Ability Measure presented significant content differences, with common participant-generated lower extremity responses at all levels. The Patient-Reported Outcomes Measurement Information System; modified Disablement of the Physically Active Scale; KOOS; IKDC; Disabilities of the Arm, Shoulder and Hand; Functional Arm Scale for Throwers; and Kerlan-Jobe Orthopaedic Clinic questionnaire did not have significant content differences for level 2 codes; still, significant differences were present for level 3 analyses except for the KOOS and IKDC (P < .001). All measures except the IKDC contained significant superfluous content (P < .05). CONCLUSIONS: The presence of significant content differences supports clinician-perceived barriers regarding the relevance of established PROMs. However, the IKDC was a relevant and efficient PROM for evaluating the primary concerns of collegiate athletes experiencing lower extremity injury. Clinicians should consider using patient-generated measures to support coverage of patient-specific concerns in care.

Priorities for pulmonary hypertension research: A James Lind Alliance priority setting partnership.

Pulmonary hypertension (PH) is a rare condition associated with significant morbidity and mortality. The priorities for future research in PH according to patients, caregivers, and clinicians have not been established. We performed a James Lind Alliance priority setting partnership in Canada. An initial survey of 249 respondents (76% patients and/or caregivers, 12.5% clinicians) generated 1588 questions, which were combined into 187 summary questions. An evidence check identified 352 systematic reviews and guidelines which were mapped to the summary questions, which determined that 157 summary questions were unanswered by existing research. An interim prioritisation survey (240 respondents, 66% patients and/or caregivers, 18% clinicians) asked respondents to choose which of the 157 summary questions were among the 30-40 most important. In a final workshop patients, caregivers, and clinicians discussed and ranked the top 25 questions from the interim survey to identify the Top 10 PH research priorities. These results will inform researchers and funding bodies about patient, caregiver, and clinician priorities for future research on PH.

Systematic Review of Clinical Results After Medial Meniscus Allograft Transplantation Reveals Improved Patient Reported Outcomes at Greater Than 5 Years Follow-Up.

PURPOSE: To systematically summarize the medial meniscus allograft transplantation (MAT) reported outcomes and evaluate whether the surgical technique is associated with allograft extrusion and knee function. METHODS: Systematic review was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Inclusion criteria were English-language clinical studies involving arthroscopically assisted medial MAT that reported the surgical technique and the presence of graft extrusion or functional outcomes after surgery. Studies in which outcomes for medial MAT could not be separated from lateral MAT were excluded. Surgical technique, allograft-related characteristics, and clinical outcomes were extracted. RESULTS: Twenty-four studies with 328 medial MAT were included, 58.3% studies qualified as level 4 of evidence, 29.2% as level 3, and 12.5% as level 2. Allograft fixation techniques were bone plug (235/328 [71.6%]), bone bridge/trough (55/328 [16.8%]), and soft-tissue suture fixation only (38/328 [11.6%]). Relative percentage of extrusion after surgery ranged from 24.8% to 53.7%. Major extrusion (>3 mm) ranged from zero to 78%. Overall, functional scores improved after medial MAT. None of surgical techniques were associated with poor functional outcomes or extruded meniscus; however, nonanatomical placement of the anterior and posterior horns appeared to increase meniscus extrusion. CONCLUSION: Medial MAT provides favorable outcomes, with acceptable rates of complication and failure regardless of surgical technique. Although allograft extrusion appears equivalent for both bone plug and soft-tissue fixation techniques, positioning allograft horns at the native meniscal footprint may be critical for preventing extrusion. However, the heterogeneity and low level of evidence of the studies included in this review prevent decisive conclusions regarding optimal MAT fixation techniques, clinical significance of allograft extrusion, or comparative clinical outcomes after medial MAT. LEVEL OF EVIDENCE: Level IV - systematic review of Level II to IV studies.

Integrating blue: How do we make nationally determined contributions work for both blue carbon and local coastal communities?

Blue Carbon Ecosystems (BCEs) help mitigate and adapt to climate change but their integration into policy, such as Nationally Determined Contributions (NDCs), remains underdeveloped. Most BCE conservation requires community engagement, hence community-scale projects must be nested within the implementation of NDCs without compromising livelihoods or social justice. Thirty-three experts, drawn from academia, project development and policy, each developed ten key questions for consideration on how to achieve this. These questions were distilled into ten themes, ranked in order of importance, giving three broad categories of people, policy & finance, and science & technology. Critical considerations for success include the need for genuine participation by communities, inclusive project governance, integration of local work into national policies and practices, sustaining livelihoods and income (for example through the voluntary carbon market and/or national Payment for Ecosystem Services and other types of financial compensation schemes) and simplification of carbon accounting and verification methodologies to lower barriers to entry.

Mindfulness Matters: Use and Perceptions of Mindfulness Practices Among Athletic Trainers.

CONTEXT: Mindfulness practices are effective for injury or illness recovery, decreasing stress and anxiety, and strengthening emotional resilience. They are also beneficial for health care professionals' wellbeing and improving patient outcomes and safety. However, mindfulness has not been studied in athletic trainers. OBJECTIVE: To investigate athletic trainers' use of mindfulness practices and their perceptions of its importance for self-care and patient or client care. DESIGN: Cross-sectional study. SETTING: All athletic training practice settings. PATIENTS AND OTHER PARTICIPANTS: A total of 547 athletic trainers who were currently practicing completed the survey. MAIN OUTCOME MEASURE(S): We developed an 18-item survey that measured use (1 = never to 6 = very frequently) and perceptions (1 = strongly disagree to 7 = strongly agree) of mindfulness practices. Mann-Whitney U or Kruskal-Wallis tests with post hoc pairwise comparisons were performed to assess differences in use (P < .05). A related-samples Wilcoxon signed rank test was calculated to assess differences in participants' perceptions between self-care and patient or client care. RESULTS: Overall, 86% (n = 471) of respondents reported involvement in some form of mindfulness practice, with females (median [interquartile range] = 4 [2-5] versus males: 3 [2-4]; P < .002), those not in a committed relationship (4 [2-5] versus those in such a relationship: 3 [2-4]; P = .048), and those without children in the home (4 [2-5] versus those with children in the home: 3 [2-4]; P = .040) describing the highest frequency of use for self-care. Females (4 [2-4] versus males: 3 [2-4]; P < .001), those without children in the home (3 [2-4] versus those with children in the home: 3 [2-4]; P = .036), and those in emerging (4 [2-4]; P = .003) or collegiate (3 [2-4]; P = .006) settings most frequently incorporated mindfulness into patient or client care. Overall frequency of use for self-care was higher than for patient or client care (4 = occasionally [2-4] versus 3 = rarely [2-4]; P < .001). Mindfulness practices were perceived as more important for self-care than for patient or client care (6 [5-7] versus 5 [5-6]; P < .001). CONCLUSIONS: Athletic trainers perceived mindfulness practices as more important for personal wellbeing and used them, albeit occasionally, more for self-care than for patient or client care. Differences in gender, relationship status, children, and setting were observed. Mindfulness-based interventions for athletic trainer wellbeing and patient-centered care and implementation barriers should be explored.

Incremental peritoneal dialysis is a safe and feasible prescription in incident patients with preserved residual kidney function.

BACKGROUND: Incremental peritoneal dialysis (PD) is recommended as a component of high-quality care by the international society for PD; however, its feasibility and clinical outcomes have not been widely reported. The aim of this study is to describe our experience with incremental PD. METHODS: This was a retrospective cohort study of incident PD patients at Eastern Health between 2015 and 2019. Patients who stopped PD within 30 days were excluded. Incremental PD was defined in CAPD as using <8 L/day of exchange volume and in automated PD as dialysing without a last fill. Dialysis modality accorded with patient and physician preferences. RESULTS: The 96 patients were included in this study; 54 with incremental PD. Compared to full-dose PD, incremental PD patients were more likely to be female, had less comorbid diabetes (28% vs. 52%) and higher residual kidney function (RKF) (Kt/V 2.0 ± 0.7 vs. 1.4 ± 0.7). Age, BMI and starting eGFR did not differ between groups. Incremental PD exposed patients to lower exchange volumes (4.4 ± 2.1 vs. 8.5 ± 1.1 L/day), glucose load (46 ± 41 g/day vs. 119 ± 46) and was associated with a longer peritonitis-free survival. PD technique survival, rates of peritonitis or hospitalization were comparable between groups. Predictors for longer incremental PD use included older age and higher starting eGFR. CONCLUSIONS: Incremental PD is a feasible, goal-directed initial prescription in patients with RKF with comparable peritonitis rates and technique survival. Validation of this prescription in prospective studies is warranted.

Bacterial infection in dogs with aspiration pneumonia at 2 tertiary referral practices.

BACKGROUND: In dogs, antimicrobial drugs are widely prescribed for aspiration pneumonia (AP) despite poor documentation of bacterial infection in AP (b-AP) using bronchoalveolar lavage fluid (BALF) analysis. Interpretating discordant cytology and culture results is challenging, contributing to lack of a criterion standard, and highlighting differences between veterinary and human medical criteria for b-AP. OBJECTIVES: Determine how many dogs with AP had BALF collection and differences in diagnosis of b-AP using veterinary vs human medical criteria. Report findings of noninvasive markers (e.g. fever, band neutrophilia, radiographic severity score) in dogs with and without b-AP. ANIMALS: Retrospective cohort study of client-owned dogs (n = 429) with AP at 2 university veterinary hospitals. Twenty-four dogs met enrollment criteria. METHODS: Inclusion criteria were radiographic diagnosis of AP, ≥1 risk factor, CBC findings, and BALF cytology and culture results. Veterinary medical b-AP criteria were cytology findings compatible with sepsis with or without positive culture, or cytology findings not consistent with sepsis and positive culture (≥1.7 × 103  cfu/mL). Human medical b-AP criteria required culture with ≥104  cfu/mL or > 7% cells with intracellular bacteria on cytology. RESULTS: Only 24/429 dogs met all enrollment criteria; 379/429 dogs lacked BALF collection. Diagnosis of b-AP differed using veterinary (79%) vs human (29%) medical criteria. Fever, band neutrophils and high radiographic scores were noted in dogs with and without b-AP. CONCLUSIONS AND CLINICAL IMPORTANCE: Lack of routine BALF collection hampers definitive recognition of bacterial infection in AP. Differences in dogs meeting veterinary vs human medical definitions for b-AP and usefulness of noninvasive markers warrant further study to improve understanding of the role of bacteria in AP.

IL-18R-mediated HSC quiescence and MLKL-dependent cell death limit hematopoiesis during infection-induced shock.

Severe infection can dramatically alter blood production, but the mechanisms driving hematopoietic stem and progenitor cell (HSC/HSPC) loss have not been clearly defined. Using Ixodes ovatus Ehrlichia (IOE), a tick-borne pathogen that causes severe shock-like illness and bone marrow (BM) aplasia, type I and II interferons (IFNs) promoted loss of HSPCs via increased cell death and enforced quiescence. IFN-αß were required for increased interleukin 18 (IL-18) expression during infection, correlating with ST-HSC loss. IL-18 deficiency prevented BM aplasia and increased HSC/HSPCs. IL-18R signaling was intrinsically required for ST-HSC quiescence, but not for HSPC cell death. To elucidate cell death mechanisms, MLKL- or gasdermin D-deficient mice were infected; whereas Mlkl-/- mice exhibited protected HSC/HSPCs, no such protection was observed in Gsdmd-/- mice during infection. MLKL deficiency intrinsically protected HSCs during infection and improved hematopoietic output upon recovery. These studies define MLKL and IL-18R signaling in HSC loss and suppressed hematopoietic function in shock-like infection.

Radiation-Induced Macrophage Senescence Impairs Resolution Programs and Drives Cardiovascular Inflammation.

Radiation is associated with tissue damage and increased risk of atherosclerosis, but there are currently no treatments and a very limited mechanistic understanding of how radiation impacts tissue repair mechanisms. We uncovered that radiation significantly delayed temporal resolution programs that were associated with decreased efferocytosis in vivo. Resolvin D1 (RvD1), a known proresolving ligand, promoted swift resolution and restored efferocytosis in sublethally irradiated mice. Irradiated macrophages exhibited several features of senescence, including increased expression of p16INK4A and p21, heightened levels of SA-ß-gal, COX-2, several proinflammatory cytokines/chemokines, and oxidative stress (OS) in vitro, and when transferred to mice, they exacerbated inflammation in vivo. Mechanistically, heightened OS in senescent macrophages led to impairment in their ability to carry out efficient efferocytosis, and treatment with RvD1 reduced OS and improved efferocytosis. Sublethally irradiated Ldlr -/- mice exhibited increased plaque necrosis, p16INK4A cells, and decreased lesional collagen compared with nonirradiated controls, and treatment with RvD1 significantly reduced necrosis and increased lesional collagen. Removal of p16INK4A hematopoietic cells during advanced atherosclerosis with p16-3MR mice reduced plaque necrosis and increased production of key intraplaque-resolving mediators. Our results demonstrate that sublethal radiation drives macrophage senescence and efferocytosis defects and suggest that RvD1 may be a new therapeutic strategy to limit radiation-induced tissue damage.