Osteoporotic thoracolumbar spine fractures in the elderly: alterations in GNRI and BMP-2 in delayed union and associated factors.

Objective: To investigate the alterations in the Geriatric Nutritional Risk Index (GNRI) and bone morphogenetic protein 2 (BMP-2) levels and identify associated factors in older adults with delayed union of osteoporotic thoracolumbar spine fractures.

Methods: From June 2021 to June 2023, 139 elderly patients with osteoporotic thoracolumbar spine fractures were selected and divided into a delayed group and a normal group according to the fracture healing status at 6 months postoperatively. GNRI and BMP-2 levels were assessed in both cohorts.

Epidemiology and Outcomes of Antibiotic De-escalation in Patients with Suspected Sepsis in US Hospitals.

Background: Little is known about the frequency, hospital-level variation, predictors, and clinical outcomes of antibiotic de-escalation in suspected sepsis.

Methods: We retrospectively analyzed all adults admitted to 236 US hospitals between 2017-2021 with suspected sepsis (defined by a blood culture draw, lactate measurement, and intravenous antibiotic administration) who were initially treated with ≥2 days of anti-MRSA and anti-pseudomonal antibiotics but had no resistant organisms requiring these agents identified through hospital day 4. De-escalation was defined as stopping anti-MRSA and anti-pseudomonal antibiotics or switching to narrower antibiotics by day 4.

Trends in Empiric Broad-Spectrum Antibiotic Use for Suspected Community-Onset Sepsis in US Hospitals.

Importance: Little is known about the degree to which suspected sepsis drives broad-spectrum antibiotic use in hospitals, what proportion of antibiotic courses are unnecessarily broad in retrospect, and whether these patterns are changing over time.

Objective: To describe trends in empiric broad-spectrum antibiotic use for suspected community-onset sepsis.

Design, Setting, And Participants: This cross-sectional study used clinical data from adults admitted to 241 US hospitals in the PINC AI Healthcare Database.

Association Between Implementation of the Severe Sepsis and Septic Shock Early Management Bundle Performance Measure and Outcomes in Patients With Suspected Sepsis in US Hospitals.

Importance: In October 2015, the Centers for Medicare & Medicaid Services began requiring US hospitals to report adherence to the Severe Sepsis and Septic Shock Early Management Bundle (SEP-1).

Objective: To evaluate the association of SEP-1 implementation with sepsis treatment patterns and outcomes in diverse hospitals.

Design, Setting, And Participants: This retrospective cohort study with interrupted time-series analysis and logistic regression models was conducted among adults admitted to 114 hospitals from October 2013 to December 2017 with suspected sepsis (blood culture orders, ≥2 systemic inflammatory response syndrome criteria, and acute organ dysfunction) within 24 hours of hospital arrival.

Impact of Risk Adjustment Using Clinical vs Administrative Data on Hospital Sepsis Mortality Comparisons.

Background: A reliable risk-adjusted sepsis outcome measure could complement current national process metrics by identifying outlier hospitals and catalyzing additional improvements in care. However, it is unclear whether integrating clinical data into risk adjustment models identifies similar high- and low-performing hospitals compared with administrative data alone, which are simpler to acquire and analyze.

Methods: We ranked 200 US hospitals by their Centers for Disease Control and Prevention Adult Sepsis Event (ASE) mortality rates and assessed how rankings changed after applying (1) an administrative risk adjustment model incorporating demographics, comorbidities, and codes for severe illness and (2) an integrated clinical and administrative model replacing severity-of-illness codes with laboratory results, vasopressors, and mechanical ventilation.

Prevalence of Antibiotic-Resistant Pathogens in Culture-Proven Sepsis and Outcomes Associated With Inadequate and Broad-Spectrum Empiric Antibiotic Use.

Importance: Broad-spectrum antibiotics are recommended for all patients with suspected sepsis to minimize the risk of undertreatment. However, little is known regarding the net prevalence of antibiotic-resistant pathogens across all patients with community-onset sepsis or the outcomes associated with unnecessarily broad empiric treatment.

Objective: To elucidate the epidemiology of antibiotic-resistant pathogens and the outcomes associated with both undertreatment and overtreatment in patients with culture-positive community-onset sepsis.

Membrane docking geometry of GRP1 PH domain bound to a target lipid bilayer: an EPR site-directed spin-labeling and relaxation study.

The second messenger lipid PIP(3) (phosphatidylinositol-3,4,5-trisphosphate) is generated by the lipid kinase PI3K (phosphoinositide-3-kinase) in the inner leaflet of the plasma membrane, where it regulates a broad array of cell processes by recruiting multiple signaling proteins containing PIP(3)-specific pleckstrin homology (PH) domains to the membrane surface. Despite the broad importance of PIP(3)-specific PH domains, the membrane docking geometry of a PH domain bound to its target PIP(3) lipid on a bilayer surface has not yet been experimentally determined. The present study employs EPR site-directed spin labeling and relaxation methods to elucidate the membrane docking geometry of GRP1 PH domain bound to bilayer-embedded PIP(3).

Functional characterization of the re-face loop spanning residues 536-541 and its interactions with the cofactor in the flavin mononucleotide-binding domain of flavocytochrome P450 from Bacillus megaterium.

Flavocytochrome P450BM-3, a bacterial monooxygenase, contains a flavin mononucleotide-binding domain bearing a strong structural homology to the bacterial flavodoxin. The flavin mononucleotide (FMN) serves as the one-electron donor to the heme iron, but in contrast to the electron transfer mechanism of mammalian cytochrome P450 reductase, the FMN semiquinone state is not thermodynamically stable and appears transiently as the anionic rather than the neutral form. A unique loop region comprised of residues (536)Y-N-G-H-P-P(541), which forms a type I' reverse turn and provides several interactions with the FMN isoalloxazine ring, was targeted in this study.

Effect of the Insertion of a Glycine Residue into the Loop Spanning Residues 536-541 on the Semiquinone State and Redox Properties of the Flavin Mononucleotide-Binding Domain of Flavocytochrome P450BM-3 from Bacillus megaterium.

Despite sharing sequence and structural similarities with other diflavin reductases such as NADPH-cytochrome P450 reductase (CPR) and nitric oxide synthase, flavocytochrome P450BM-3 displays some unique redox and electron transferring properties, including the inability to thermodynamically stabilize the neutral semiquinone (SQ) state of the flavin mononucleotide (FMN) cofactor. Rather, the anionic SQ species is only transiently formed during rapid reduction. Why is this? The absence of a conserved glycine residue and, as a consequence, the shorter and less flexible cofactor-binding loop in P450BM-3 represents a notable difference from other diflavin reductases and the structurally related flavodoxin.