The prevalence of blood product transfusion after the implementation of a postpartum hemorrhage bundle: a retrospective cohort at a single safety net academic institution.

BACKGROUND: Postpartum hemorrhage, defined as blood loss of ≥1000 mL within 24 hours after birth, is a leading cause of maternal morbidity and is associated with substantial financial and emotional burden. Based on societal and regulatory guidelines, in 2019, our institution adopted a postpartum hemorrhage prevention and management bundle based on the California Maternal Quality Care Collaborative initiatives. OBJECTIVE: The study aimed to compare the prevalence of maternal blood product transfusion before and after the implementation of the bundle. STUDY DESIGN: This was a retrospective cohort study comparing the prevalence of blood product transfusion before and after the implementation of a California Maternal Quality Care Collaborative-based postpartum hemorrhage management bundle at a single safety net teaching hospital between October 2017 and December 2019 excluding a 4-month rollout period between September 2018 and December 2018. The study included all patients ≥18 years of age and at >20 weeks' gestation. Exclusion criteria were out-born deliveries, delivery at time of significant nonobstetrical trauma, and refusal of blood transfusion. The primary outcome was the frequency of any blood product transfusion in the pre- and postbundle implementation cohorts. Secondary outcomes included blood product transfusion type and amount, maternal death, intrauterine balloon placement, uterine artery embolization, unplanned peripartum hysterectomy, intensive care admission, and length of stay among all deliveries complicated by postpartum hemorrhage. We further evaluated compliance with bundle measures for all postpartum hemorrhage cases. Cohort characteristics were compared using chi-square tests or Fisher exact tests for categorical data and Satterthwaite or Wilcoxon 2-sample tests for continuous variables based on data distributions. The proportion of blood product transfusion were evaluated using a chi-square test. RESULTS: A total of 6744 deliveries were included with 3310 in the pre- and 3425 in the postbundle cohort. The prevalence of any blood product transfusion was similar between the pre- and postbundle cohorts (3.41%; 113/3310 vs 3.47%; 119/3425; P=.892). The prevalence of postpartum hemorrhage was 7.05% (233/3310) in the prebundle cohort and 10.34% (354/3434) in the postbundle cohort (P<.001). Among women with postpartum hemorrhage, those in the prebundle cohort had a higher rate of blood product transfusion than those in the postbundle cohort (36.05%; 84/233 vs 26.84%; 95/354; P=.018). Compared with the prebundle counterparts, patients with postpartum hemorrhage in the postbundle cohort had higher rates of utilization of intrauterine balloon placement (10.30%; 24/233 vs 16.95%; 60/354; P=.024). There were no significant differences among other secondary outcomes. The overall compliance with the bundle among those with blood loss ≥1000 mL was 92.1%. CONCLUSION: The implementation of the postpartum hemorrhage bundle did not decrease the overall prevalence of blood product transfusion and may have led to higher rates of utilization of resources.

T Cell-Independent Gamma Interferon and B Cells Cooperate To Prevent Mortality Associated with Disseminated Chlamydia muridarum Genital Tract Infection.

CD4 T cells and antibody are required for optimal acquired immunity to Chlamydia muridarum genital tract infection, and T cell-mediated gamma interferon (IFN-γ) production is necessary to clear infection in the absence of humoral immunity. However, the role of T cell-independent immune responses during primary infection remains unclear. We investigated this question by inoculating wild-type and immune-deficient mice with C. muridarum CM001, a clonal isolate capable of enhanced extragenital replication. Genital inoculation of wild-type mice resulted in transient dissemination to the lungs and spleen that then was rapidly cleared from these organs. However, CM001 genital infection proved lethal for STAT1-/- and IFNG-/- mice, in which IFN-γ signaling was absent, and for Rag1-/- mice, which lacked T and B cells and in which innate IFN-γ signaling was retained. In contrast, B cell-deficient muMT mice, which can generate a Th1 response, and T cell-deficient mice with intact B cell and innate IFN-γ signaling survived. These data collectively indicate that IFN-γ prevents lethal CM001 dissemination in the absence of T cells and suggests a B cell corequirement. Adoptive transfer of convalescent-phase immune serum but not naive IgM to Rag1-/- mice infected with CM001 significantly increased the survival time, while transfer of naive B cells completely rescued Rag1-/- mice from CM001 lethality. Protection was associated with a significant reduction in the lung chlamydial burden of genitally infected mice. These data reveal an important cooperation between T cell-independent B cell responses and innate IFN-γ in chlamydial host defense and suggest that interactions between T cell-independent antibody and IFN-γ are essential for limiting extragenital dissemination.

Phenology of brown marmorated stink bug described using female reproductive development.

Temperature-based degree-day models describe insect seasonality and to predict key phenological events. We expand on the use of a temperature-based process defining timing of reproduction through the incorporation of female reproductive physiology for the invasive pentatomid species Halyomorpha halys, the brown marmorated stink bug. A five-stage ranking system based on ovary development was able to distinguish between the reproductive statuses of field-collected females. Application of this ranking method described aspects of H. halys' seasonality, overwintering biology, and phenology across geographic locations. Female H. halys were collected in the US from NJ, WV, NC, OR, and two sites in PA in 2006-2008 (Allentown, PA only) and 2012-2014. Results identify that H. halys enters reproductive diapause in temperate locations in the fall and that a delay occurs in developmental maturity after diapause termination in the spring. Modification of the Snyder method to identify biofix determined 12.7-hr photoperiod as the best fit to define initiation of reproduction in the spring. Applying the biofix, we demonstrated significant differences between locations for the rate at which the overwintering generation transition into reproductive status and the factors contributing to this difference require further study. For example, after including abiotic variables influencing development such as temperature and photoperiod (critical diapause cue), reproduction occurred earlier in OR and for an extended period in NJ. This data describe a method to investigate insect seasonality by incorporating physiological development across multiple regions that can clarify phenology for insects with overlapping generations.

Comparable Genital Tract Infection, Pathology, and Immunity in Rhesus Macaques Inoculated with Wild-Type or Plasmid-Deficient Chlamydia trachomatis Serovar D.

Rhesus macaques were studied to directly address the potential for plasmid-deficient Chlamydia trachomatis to serve as a live attenuated vaccine in the genital tract. Five repeated cervical inoculations of rhesus macaques with wild-type serovar D strain D/UW-3/Cx or a plasmid-deficient derivative of this strain, CTD153, resulted in infections with similar kinetics and induced comparable levels of protective immunity. After all animals received five challenges with D/UW-3/Cx, levels of inflammation observed grossly and histologically were similar between the groups. Animals in both groups developed evidence of oviduct dilatation; however, reduced oviduct dilatation was observed for "controllers," i.e., animals without detectable chlamydial DNA in the fimbriae at weeks 5 and 12. Grouping animals into "ascenders" and "controllers" revealed that elevated early T cell responses were associated with protection, whereas higher antibody responses were associated with ascension. Protected animals shared common major histocompatibility complex (MHC) alleles. Overall, genetic differences of individual animals, rather than the presence or absence of the chlamydial plasmid in the primary infecting strain, appeared to play a role in determining the outcome of infection.

Steroids alone or as adjunctive therapy with doxycycline fail to improve oviduct damage in mice infected with Chlamydia muridarum.

In women, Chlamydia trachomatis can ascend from the cervix to the fallopian tubes, where an overly aggressive host inflammatory response can cause scarring that leads to chronic pelvic pain, infertility, or ectopic pregnancy. Although screening and treatment programs for women have resulted in decreased rates of sequelae, morbidities associated with oviduct scarring continue to occur. Since corticosteroids have anti-inflammatory and antifibrotic effects, we tested the ability of dexamethasone to inhibit inflammation and prevent oviduct scarring in mice genitally infected with Chlamydia muridarum. The administration of 1 or 2.5 mg/kg of body weight of dexamethasone on days 7 to 21 of infection resulted in reduced accumulation of inflammatory cells in the oviducts compared to that in controls. However, a concomitant increase in bacterial burden was observed, and chronic oviduct disease was not reduced. Adjunctive administration of a prolonged (21-day) or short (3-day) course of dexamethasone in combination with the antibiotic doxycycline also failed to reduce chronic oviduct pathology compared to antibiotic treatment alone. Steroids administered alone or adjunctively with antibiotics failed to prevent oviduct damage in this murine model of C. trachomatis infection.

IL-23 induces IL-22 and IL-17 production in response to Chlamydia muridarum genital tract infection, but the absence of these cytokines does not influence disease pathogenesis.

OBJECTIVE: Chlamydia trachomatis infections are a significant cause of reproductive tract pathology. Protective and pathological immune mediators must be differentiated to design a safe and effective vaccine. METHODS: Wild-type mice and mice deficient in IL-22 and IL-23 were infected intravaginally with Chlamydia muridarum, and their course of infection and oviduct pathology were compared. Local genital tract and draining lymph node immune responses were also examined in IL-23-deficient mice. RESULTS: IL-22- and IL-23-deficient mice exhibited normal susceptibility to infection and oviduct pathology. IL-23 was required for the development of a Chlamydia-specific Th17 response in the lymph nodes and for production of IL-22 and IL-17 in the genital tract. However, influx of Th1 and innate immune cells was not compromised in the absence of IL-23. CONCLUSION: IL-22 and IL-23 play either redundant or minimal roles in the pathogenesis of Chlamydia infection in the mouse model. Induction of Th17-associated cytokines by a Chlamydia vaccine should be avoided as these responses are not central to resolution of infection and have pathologic potential.

CD4+ T cell expression of MyD88 is essential for normal resolution of Chlamydia muridarum genital tract infection.

Resolution of Chlamydia genital tract infection is delayed in the absence of MyD88. In these studies, we first used bone marrow chimeras to demonstrate a requirement for MyD88 expression by hematopoietic cells in the presence of a wild-type epithelium. Using mixed bone marrow chimeras we then determined that MyD88 expression was specifically required in the adaptive immune compartment. Furthermore, adoptive transfer experiments revealed that CD4(+) T cell expression of MyD88 was necessary for normal resolution of genital tract infection. This requirement was associated with a reduced ability of MyD88(-/-)CD4(+) T cells to accumulate in the draining lymph nodes and genital tract when exposed to the same inflammatory milieu as wild-type CD4(+) T cells. We also demonstrated that the impaired infection control we observed in the absence of MyD88 could not be recapitulated by deficiencies in TLR or IL-1R signaling. In vitro, we detected an increased frequency of apoptotic MyD88(-/-)CD4(+) T cells upon activation in the absence of exogenous ligands for receptors upstream of MyD88. These data reveal an intrinsic requirement for MyD88 in CD4(+) T cells during Chlamydia infection and indicate that the importance of MyD88 extends beyond innate immune responses by directly influencing adaptive immunity.

Design and preparation of a core-shell metal-organic framework for selective CO2 capture.

The design of a core-shell metal-organic framework comprising a porous bio-MOF-11/14 mixed core and a less porous bio-MOF-14 shell is reported. The growth of the MOF shell was directly observed and supported by SEM and PXRD. The resulting core-shell material exhibits 30% higher CO2 uptake than bio-MOF-14 and low N2 uptake in comparison to the core. When the core-shell architecture is destroyed by fracturing the crystallites via grinding, the amount of N2 adsorbed doubles but the CO2 adsorption capacity remains the same. Finally, the more water stable bio-MOF-14 shell serves to prevent degradation of the water-sensitive core in aqueous environments, as evidenced by SEM and PXRD.

Early ultrafiltration in patients with decompensated heart failure and diuretic resistance.

OBJECTIVES: We sought to determine if ultrafiltration before intravenous (IV) diuretics in patients with decompensated heart failure and diuretic resistance results in euvolemia and early discharge without hypotension or worsening renal function. BACKGROUND: Heart failure patients with renal insufficiency and diuretic resistance have increased hospital mortality and length of stay. Peripheral veno-venous ultrafiltration may re-establish euvolemia and diuretic responsiveness. METHODS: Ultrafiltration was initiated within 4.7 +/- 3.5 h of hospitalization and before IV diuretics in 20 heart failure patients with volume overload and diuretic resistance (age 74.5 +/- 8.2 years; 75% ischemic disease; ejection fraction 31 +/- 15%) and continued until euvolemia. Re-evaluation was each hospital day, at 30 days, and at 90 days. RESULTS: A total of 8,654 +/- 4,205 ml were removed with ultrafiltration. Twelve patients (60%) were discharged in < or =3 days. One patient was readmitted in 30 days. Weight (p = 0.006), Minnesota Living with Heart Failure scores (p = 0.003), and Global Assessment (p = 0.00003) improved after ultrafiltration and at 30 and 90 days. Median B-type natriuretic peptide levels decreased after ultrafiltration (from 1,230 pg/ml to 788 pg/ml) and at 30 days (815 pg/ml) (p = 0.035). Blood pressure, renal function, and medications were unchanged. CONCLUSIONS: In heart failure patients with volume overload and diuretic resistance, ultrafiltration before IV diuretics effectively and safely decreases length of stay and readmissions. Clinical benefits persist at three months.