Transcriptional Profiling of Phagocytic Leukocytes and Microglia Reveals a Critical Role for Reactive Oxygen Species in Biofilm Containment during Staphylococcus aureus Craniotomy Infection.

Craniotomies are performed to treat a variety of intracranial pathology. Surgical site infection remains a complication of craniotomy despite the use of prophylactic antibiotics and universal sterile precautions. Infections occur in 1-3% of procedures, with approximately half caused by Staphylococcus aureus that forms a biofilm on the bone flap and is recalcitrant to systemic antibiotic therapy. We used an S. aureus-dsRed construct to compare the phagocytic capacity of leukocytes and microglia in vitro and in vivo using a mouse model of craniotomy infection. In addition, single-cell RNA sequencing (scRNA-seq) was applied to determine whether a transcriptional signature could be identified for phagocytic versus nonphagocytic cells in vivo. S. aureus was phagocytosed to equivalent extents in microglia, macrophages, neutrophils, and granulocytic myeloid-derived suppressor cells in vitro; however, microglial uptake of S. aureus was limited in vivo, whereas the other leukocyte populations exhibited phagocytic activity. scRNA-seq comparing the transcriptional signatures of phagocytic (S. aureus-dsRed+) versus nonphagocytic (S. aureus-dsRed-) leukocytes identified classical pathways enriched in phagocytic cells (i.e., reactive oxygen species [ROS]/reactive nitrogen species, lysosome, iron uptake, and transport), whereas nonphagocytic populations had increased ribosomal, IFN, and hypoxia signatures. scRNA-seq also revealed a robust ROS profile, which led to the exploration of craniotomy infection in NADPH oxidase 2 knockout mice. S. aureus burden, leukocyte recruitment, and intracellular bacterial load were significantly increased in NADPH oxidase 2 KO compared with wild-type animals. Collectively, these results highlight the importance of ROS generation in phagocytes for S. aureus biofilm containment, but not clearance, during craniotomy infection.

Transcriptional Diversity and Niche-Specific Distribution of Leukocyte Populations during Staphylococcus aureus Craniotomy-Associated Biofilm Infection.

Neurosurgery for brain tumor resection or epilepsy treatment requires a craniotomy to gain access to the brain. Despite prophylactic measures, infectious complications occur at a frequency of 1-3%, with approximately half caused by Staphylococcus aureus (S. aureus) that forms a biofilm on the bone flap and is recalcitrant to antibiotics. Using single-cell RNA sequencing in a mouse model of S. aureus craniotomy infection, this study revealed the complex transcriptional heterogeneity of resident microglia and infiltrating monocytes in the brain, in addition to transcriptionally diverse granulocyte subsets in the s.c. galea and bone flap. In the brain, trajectory analysis identified the transition of microglia from a homeostatic/anti-inflammatory to proinflammatory and proliferative populations, whereas granulocytes in the brain demonstrated a trajectory from a granulocyte myeloid-derived suppressor cell (MDSC)-like phenotype to a small population of mature polymorphonuclear neutrophils (PMNs). In the galea, trajectory analysis identified the progression from two distinct granulocyte-MDSC-like populations to PMN clusters enriched for IFN signaling and cell cycle genes. Based on their abundance in the galea and bone flap, PMNs and MDSCs were depleted using anti-Ly6G, which resulted in increased bacterial burden. This revealed a critical role for PMNs in S. aureus containment because MDSCs were found to attenuate PMN antibacterial activity, which may explain, in part, why craniotomy infection persists in the presence of PMN infiltrates. These results demonstrate the existence of a transcriptionally diverse leukocyte response that likely influences the chronicity of S. aureus craniotomy infection.

Time Required for Gross Examination of Routine Second and Third Trimester Singleton Placentas by Pathologists' Assistants.

INTRODUCTION: In both Canada and the United States, workload measurement for anatomic pathology is mainly based on complexity and clinical significance of specimens, with gross examination being a considerable contributor. While Pathologists' Assistants (PAs) play an increasing role in gross examination, there is little known regarding the time required for PAs to complete grossing tasks. This information is essential for effective staffing and workload management in pathology laboratories. The objective of our study was to determine the time required for PAs to gross second and third trimester singleton placentas in a large tertiary hospital with a significant perinatal pathology service. MATERIALS AND METHODS: For our study, 7 certified PAs each grossed a minimum of 10 second and third trimester singleton placentas using a standard placental grossing protocol, an electronic laboratory information system, and voice recognition dictation software. Placental specimens requiring photography, sampling for ancillary studies, or immediate pathologist's consultation were excluded. We calculated average and standard deviation of grossing times for each PA, overall average grossing time, and 95% confidence interval using a mixed linear regression model. We analyzed the impact of PA job experience, degree obtained, and number of blocks prepared on overall average in a multivariate analysis. RESULTS: The mean grossing times for each PA ranged from 11.0 (standard deviation [sd] = 2.0) to 17.8 (sd = 4.5) minutes. The overall average grossing time was 14.5 minutes, with a 95% confidence interval of 11.7 to 17.3 minutes. In multivariate analysis, an increase in the number of blocks prepared was significantly associated with longer overall average grossing time. If 4 blocks were prepared consistently, the model predicted a slightly lower overall average of 13.3 minutes, with a 95% confidence interval of 10.9 to 15.7 minutes. DISCUSSION: To our knowledge, our study is the first to objectively report time required for PAs to perform gross examinations of routine second and third trimester singleton placentas. The methodology of our study is replicable and can be applied to other specimen types and laboratory settings. Previously, estimated grossing times for specimens were primarily based on retrospective surveys, which were susceptible to recall errors and subjectivity. However, our study demonstrates objective data collection is achievable. Furthermore, the data collected from this study offer valuable insights into the accuracy of previous and current pathology workload models for second and third trimester singleton placentas.

Vitelline Vessel Remnant-Derived Funisitis Is a Sensitive and Specific Predictor of Histological Evidence of Amniotic Fluid Infection.

BACKGROUND: 4-11% of umbilical cords contain vitelline vessel remnants (VVRs). A recent study has described neutrophilic inflammation arising from VVRs and suggested an association with amniotic fluid infection (AFI). METHODS: During routine placental pathology sign-out over a six month period, we identified 70 cords with VVRs. HE-stained sections were re-examined for "VVR-derived funisitis," which was classified as low or high grade/stage based upon whether neutrophils were present only in Wharton's jelly near the VVRs or whether neutrophils were also present near the cord's amniotic surface. The same placentas were also examined for histologic evidence of AFI (maternal response = acute chorionitis or chorioamnionitis vs. fetal response = chorionic vasculitis, umbilical vasculitis, or funisitis vs. both). RESULTS: Neutrophilic inflammation arising from VVRs was present in 54.3% (38/70); 15 and 23 lesions were low and high grade/stage, respectively. "VVR-derived funisitis" was strongly associated with histological evidence of AFI elsewhere in the placenta. Its overall sensitivity and specificity were 0.94 and 0.88; when VVR-derived funisitis was high grade/stage or diagnosed in the third trimester, specificity rose to 1.0. CONCLUSION: "VVR-derived funisitis" has a strong association with histological evidence of AFI.

Structure of the 5' Untranslated Region of Enteroviral Genomic RNA.

Enteroviral RNA genomes share a long, highly structured 5' untranslated region (5' UTR) containing a type I internal ribosome entry site (IRES). The 5' UTR is composed of stably folded RNA domains connected by unstructured RNA regions. Proper folding and functioning of the 5' UTR underlies the efficiency of viral replication and also determines viral virulence. We have characterized the structure of 5' UTR genomic RNA from coxsackievirus B3 using selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) and base-specific chemical probes in solution. Our results revealed novel structural features, including realignment of major domains, newly identified long-range interactions, and an intrinsically disordered connecting region. Together, these newly identified features contribute to a model for enteroviral 5' UTRs with type I IRES elements that links structure to function during the hierarchical processes directed by genomic RNA during viral infection.IMPORTANCE Enterovirus infections are responsible for human diseases, including myocarditis, pancreatitis, acute flaccid paralysis, and poliomyelitis. The virulence of these viruses depends on efficient recognition of the RNA genome by a large family of host proteins and protein synthesis factors, which in turn relies on the three-dimensional folding of the first 750 nucleotides of the molecule. Structural information about this region of the genome, called the 5' untranslated region (5' UTR), is needed to assist in the process of vaccine and antiviral development. This work presents a model for the structure of the enteroviral 5' UTR. The model includes an RNA element called an intrinsically disordered RNA region (IDRR). Intrinsically disordered proteins (IDPs) are well known, but correlates in RNA have not been proposed. The proposed IDRR is a 20-nucleotide region, long known for its functional importance, where structural flexibility helps explain recognition by factors controlling multiple functional states.

Detection of a Single-Copy Plasmid, pXFSL21, in Xylella fastidiosa Strain Stag's Leap with Two Toxin-Antitoxin Systems Using Next-Generation Sequencing.

Plasmids are important genetic elements contributing to bacterial evolution and environmental adaptation. Xylella fastidiosa is a nutritionally fastidious Gram-negative bacterium causing economically devastating diseases such as Pierce's disease (PD) of grapevine. In this study, the plasmid status of a highly virulent PD strain, Stag's Leap, originally isolated from Napa Valley, CA, was studied using sequencing and bioinformatics tools. DNA samples extracted from a pure culture in periwinkle wilt medium (in vitro DNA) and a PD-symptomatic grapevine artificially inoculated in the greenhouse (in planta DNA) were subject to next-generation sequencing (NGS) analyses (Illumina MiSeq or HiSeq). Sequence analyses and polymerase chain reaction experiments revealed the presence of a circular plasmid, pXFSL21, of 21,665 bp. This plasmid existed as a single copy per bacterial genome under both in vitro and in planta conditions. Two toxin-antitoxin (T-A) systems (ydcD-ydcE and higB-higA) were detected in pXFSL21, a possible mechanism for the long-term survival of this single-copy plasmid in the bacterial population. BLAST searches against the GenBank database (version 222) detected homologs of the two T-A systems in chromosomes or plasmids of some X. fastidiosa strains. However, double T-A systems were found only in pXFSL21. pXFSL21 was not found in other known PD strains and, therefore, could serve as a molecular marker for strain Stag's Leap monitoring and tracking. The NGS-based technique outlined in this article provides an effective tool for identifying single- or low-copy-number plasmids in fastidious prokaryotes.

Incidence, demographics, and outcomes of nonoperative management of appendicitis in the United States.

BACKGROUND: Appendicitis is the most common intraabdominal surgical emergency in the United States, with over 250,000 cases each year. Several recent studies have evaluated the efficacy of nonoperative management of appendicitis. We measured changes in the treatment of appendicitis in the United States from 1998 to 2014 and evaluated outcomes in the contemporary cohort of appendicitis cases from 2010 to 2014. METHODS: The National Inpatient Sample was queried for cases with a principal diagnosis of appendicitis. Cases with peritoneal abscesses were excluded. We determined trends in management and then compared cases managed nonoperatively versus those managed with early operation for demographics and outcomes including mortality, total charges, and length of stay using univariate analysis, binary logistic regression analysis, and case-control matching. RESULTS: Although early operation remains the dominant treatment for acute appendicitis in the United States, there is an accelerating trend in nonoperative management. Nonoperative management is associated with increased age, number of comorbidities, and inpatient diagnoses. In univariate, multiple regression, and case-control analysis, nonoperative management is associated with decreased total charges but significantly increased risk of mortality. CONCLUSIONS: Elderly patients and patients with medical comorbidities are more likely to be treated nonoperatively for appendicitis than younger patients. Although previously published data support nonoperative management of appendicitis in low-risk surgical patients, we suggest that elderly or medically complex patients may benefit from early operative treatment of appendicitis and are potentially at risk of poor outcomes from nonoperative management.

A Type 3 Prophage of 'Candidatus Liberibacter asiaticus' Carrying a Restriction-Modification System.

Prophages, the lysogenic form of bacterial phages, are important genetic entities of 'Candidatus Liberibacter asiaticus' (CLas), a nonculturable α-proteobacterium associated with citrus Huanglongbing. Two CLas prophages have been described, SC1 (NC_019549.1, Type 1) and SC2 (NC_019550.1, Type 2), which involve the lytic cycle and the lysogenic cycle, respectively. To explore the prophage repertoire, 523 CLas DNA samples extracted from leaf petioles of CLas-infected citrus were collected from southern China and surveyed for Type 1 and Type 2 prophages by specific PCR. Eighteen samples were found lacking both prophages. One sample, JXGC, sequenced using Illumina HiSeq, generated >100 million short sequence reads (150 bp per read). Read mapping to known prophage sequences showed a sequence coverage of 46% to SC1 and 50% to SC2. BLAST search using SC1 and SC2 as queries identified three contigs from the JXGC de novo assembly that form a circular P-JXGC-3 (31,449 bp), designated as a new Type 3 prophage. Chromosomal integration of P-JXGC-3 was detected to occur within a helicase gene, resulting in a duplication of this gene. P-JXGC-3 had 36 open reading frames (ORFs), 10 of which were not found in Type 1 or Type 2 prophages, including four genes that encoded a restriction-modification (R-M) system (hsdR, hsdS, hsdM1, and hsdM2). Typed by prophage-specific PCR, the CLas strains in southern China contained all combinations of the three prophage types with the exception of a Type 2-Type 3 combination, suggesting active ongoing prophage-phage interactions. Based on gene annotation, P-JXGC-3 is not capable of reproduction via the lytic cycle. The R-M system was speculated to play a role against Type 1 prophage-phage invasion.

Conjugative Plasmid Transfer in Xylella fastidiosa Is Dependent on tra and trb Operon Functions.

The insect-transmitted plant pathogen Xylella fastidiosa is capable of efficient horizontal gene transfer (HGT) and recombination. Natural transformation occurs at high rates in X. fastidiosa, but there also is evidence that certain strains of X. fastidiosa carry native plasmids equipped with transfer and mobilization genes, suggesting conjugation as an additional mechanism of HGT in some instances. Two operons, tra and trb, putatively encoding a conjugative type IV secretion system, are found in some but not all X. fastidiosa isolates, often on native plasmids. X. fastidiosa strains that carry the conjugative transfer genes can belong to different subspecies and frequently differ in host ranges. Using X. fastidiosa strain M23 (X. fastidiosa subsp. fastidiosa) or Dixon (X. fastidiosa subsp. multiplex) as the donor strain and Temecula (X. fastidiosa subsp. fastidiosa) as the recipient strain, plasmid transfer was characterized using the mobilizable broad-host-range vector pBBR5pemIK. Transfer of plasmid pBBR5pemIK was observed under in vitro conditions with both donor strains and was dependent on both tra and trb operon functions. A conjugative mechanism likely contributes to gene transfer between diverse strains of X. fastidiosa, possibly facilitating adaptation to new environments or different hosts.IMPORTANCEXylella fastidiosa is an important plant pathogen worldwide, infecting a wide range of different plant species. The emergence of new diseases caused by X. fastidiosa, or host switching of existing strains, is thought to be primarily due to the high frequency of HGT and recombination in this pathogen. Transfer of plasmids by a conjugative mechanism enables movement of larger amounts of genetic material at one time, compared with other routes of gene transfer such as natural transformation. Establishing the prevalence and functionality of this mechanism in X. fastidiosa contributes to a better understanding of HGT, adaptation, and disease emergence in this diverse pathogen.

Infected Iliac Pseudoaneurysm after Cardiac Catheterization Complicated by Girdlestone Pseudoarthroplasty for Recurrent Infection of Hip Prosthesis.

We report a massive infected pseudoaneurysm of the right external iliac artery in the setting of Girdlestone pseudoarthroplasty (GSA) for chronic infection. Around the time of her GSA, the patient underwent cardiac catheterization with resultant pseudoaneurysm formation. Infection was likely due to spread from her previous chronic infection. Delay in presentation occurred due to attribution of her symptoms to her GSA. The patient underwent ligation of the right external iliac artery and hip disarticulation and was discharged on antibiotics. At follow-up, she had significantly reduced pain. Although vascular complications from orthopedic procedures are well described, this case seems to have been caused by secondary infection of her iatrogenic external iliac artery pseudoaneurysm.

Current usage and future trends in gross digital photography in Canada.

BACKGROUND: The purpose of this study was to assess the current usage, utilization and future direction of digital photography of gross surgical specimens in pathology laboratories across Canada. METHODS: An online survey consisting of 23 multiple choice and free-text questions regarding gross digital photography was sent out to via email to laboratory staff across Canada involved in gross dissection of surgical specimens. RESULTS: Sixty surveys were returned with representation from most of the provinces. Results showed that gross digital photography is utilized at most institutions (90.0%) and the primary users of the technology are Pathologists (88.0%), Pathologists' Assistants (54.0%) and Pathology residents (50.0%). Most respondents felt that there is a definite need for routine digital imaging of gross surgical specimens in their practice (80.0%). The top two applications for gross digital photography are for documentation of interesting/ complex cases (98.0%) and for teaching purposes (84.0%). The main limitations identified by the survey group are storage space (42.5%) and security issues (40.0%). Respondents indicated that future applications of gross digital photography mostly include teaching (96.6%), presentation at tumour boards/ clinical rounds (89.8%), medico-legal documentation (72.9%) and usage for consultation purposes (69.5%). CONCLUSIONS: The results of this survey indicate that pathology staff across Canada currently utilizes gross digital images for regular documentation and educational reasons. They also show that the technology will be needed for future applications in teaching, consultation and medico-legal purposes.

Granulocytic myeloid-derived suppressor cell activity during biofilm infection is regulated by a glycolysis/HIF1a axis.

Staphylococcus aureus is a leading cause of biofilm-associated prosthetic joint infection (PJI). A primary contributor to infection chronicity is an expansion of granulocytic myeloid-derived suppressor cells (G-MDSCs), which are critical for orchestrating the antiinflammatory biofilm milieu. Single-cell sequencing and bioinformatic metabolic algorithms were used to explore the link between G-MDSC metabolism and S. aureus PJI outcome. Glycolysis and the hypoxia response through HIF1a were significantly enriched in G-MDSCs. Interfering with both pathways in vivo, using a 2-deoxyglucose nanopreparation and granulocyte-targeted Hif1a conditional KO mice, respectively, attenuated G-MDSC-mediated immunosuppression and reduced bacterial burden in a mouse model of S. aureus PJI. In addition, single-cell RNA-Seq (scRNA-Seq) analysis of granulocytes from PJI patients also showed an enrichment in glycolysis and hypoxia-response genes. These findings support the importance of a glycolysis/HIF1a axis in promoting G-MDSC antiinflammatory activity and biofilm persistence during PJI.

'Through and Through' History: The Management of Gunshot Wounds From the 14th Century to the Present.

Gun violence killed over 46,000 Americans in 2021; almost 120,000 suffered gunshot wounds. This epidemic has attracted national attention and increasing concern from medical and surgical organizations, as evident in this special issue. 'Through and Through History' explores the surgical management of gunshot wounds from their earliest appearance in 14th-century Europe to the present. Interweaving the civilian and military experience, it details not only the evolution of care directly applied to patients but also the social, political, and scientific milieu that shaped decisions made and actions performed both in and out of the operating room. The article describes how surgeons have pushed the boundaries of medicine and science in each era, developing new therapies for their patients, a historical trend that persists today when such care has the potential to save tens of thousands of lives each year.

Quality of Integration of Air Force Trauma Surgeons Within the Center for Sustainment of Trauma and Readiness Skills, Cincinnati: A Pilot Study.

INTRODUCTION: While previous studies have analyzed military surgeon experience within military-civilian partnerships (MCPs), there has never been an assessment of how well military providers are integrated within an MCP. The Center for Sustainment of Trauma and Readiness Skills, Cincinnati supports the Critical Care Air Transport Advanced Course and maintains the clinical skills of its staff by embedding them within the University of Cincinnati Medical Center. We hypothesized that military trauma surgeons are well integrated within University of Cincinnati Medical Center and that they are exposed to a similar range of complex surgical pathophysiology as their civilian partners. MATERIALS AND METHODS: After Institutional Review Board approval, Current Procedural Terminology (CPT) codes were abstracted from billing data for trauma surgeons covering University of Cincinnati Hospitals in 2019. The number of trauma resuscitations and patient acuity metrics were abstracted from the Trauma Registry and surgeon Knowledge, Skills, and Abilities clinical activity (KSA-CA) scores were calculated using their CPT codes. Finally, surgeon case distributions were studied by sorting their CPT codes into 23 categories based on procedure type and anatomic location. Appropriate, chi-squared or Mann-Whitney U-tests were used to compare these metrics between the military and civilian surgeon groups and the metrics were normalized by the group's full-time equivalent (FTE) to adjust for varying weeks on service between groups. RESULTS: Data were available for two active duty military and nine civilian staff. The FTEs were significantly lower in the military group: military 0.583-0.583 (median 0.583) vs. civilian 0.625-1.165 (median 1.0), P = 0.04. Per median FTE and surgeon number, both groups performed a similar number of trauma resuscitations (civilian 214 ± 54 vs. military 280 ± 13, P = 0.146) and KSA-CA points (civilian 55,629 ± 25,104 vs. military 36,286 ± 11,267; P = 0.582). Although the civilian surgeons had a higher proportion of hernia repairs (P < 0.001) and laparoscopic procedures (P = 0.006), the CPT code categories most relevant to combat surgery (those relating to solid organ, hollow viscus, cardiac, thoracic, abdominal, and tissue debridement procedures) were similar between the surgeon groups. Finally, patient acuity metrics were similar between groups. CONCLUSION: This is the first assessment of U.S. Air Force trauma surgeon integration relative to their civilian partners within an MCP. Normalized by FTE, there was no difference between the two groups' trauma experience to include patient acuity metrics and KSA-CA scores. The proportion of CPT codes that was most relevant to expeditionary surgery was similar between the military and civilian partners, thus optimizing the surgical experience for the military trauma surgeons within University of Cincinnati Medical Center. The methods used within this pilot study can be generalized to any American College of Surgeons verified Trauma Center MCP, as standard databases were used.

Colonoscopies in Australia - how much does the National Bowel Cancer Screening Program contribute to colonoscopy use?

Objectives and importance of study: Colorectal cancer (CRC) is Australia's fourth most commonly diagnosed cancer. CRC screening is an effective intervention to reduce this burden. The National Bowel Cancer Screening Program (NBCSP) provides 2-yearly immunochemical faecal occult blood tests (iFOBTs) to Australians aged 50-74 years; a diagnostic colonoscopy is conducted after a positive iFOBT. Clinical guidelines inform colonoscopy usage, and appropriate use of these guidelines is vital to investigate gastrointestinal symptoms, detect bowel abnormalities and CRC, and remove precancerous polyps. Colonoscopy services are under strain, with limited formal strategies to prioritise patients. There are concerns among practitioners and patient advocates that the NBCSP generates additional colonoscopy requests and increases wait times, worsening patient outcomes and prolonging distress. In this research study, we estimate and project colonoscopy use in Australia from 2001 to 2030 and determine the impact of the NBCSP by examining model-estimated NBCSP colonoscopy demand. METHODS: Colonoscopy use in Australia was compiled using Medicare Benefits Schedule (MBS) claims for colonoscopies from 2001 to 2019. From these data, projections were made from 2020 to 2030. Policy1-Bowel, a microsimulation model, was used to estimate NBCSP-related colonoscopy demand from screening follow-up and colonoscopic surveillance from 2006 to 2030. RESULTS: MBS-funded colonoscopy use increased from 284 676 in 2001 to 663 213 in 2019. Annual use is projected to be more than 780 000 by 2030. Of these, 10-14% are projected to be generated by the NBCSP. Per-capita MBS-funded colonoscopy utilisation increased 0.2% annually over 2015-2019, a slowing of growth compared to previous trends. CONCLUSION: The NBCSP accounts for a modest fraction of colonoscopy use in Australia, and a better understanding of colonoscopy use not associated with the NBCSP is needed. Promoting adherence to guideline-recommended iFOBT and colonoscopy use could ease pressure on services and improve outcomes.

The Ability of Military Critical Care Air Transport Members to Visually Estimate Percent Systolic Pressure Variation.

INTRODUCTION: Inappropriate fluid management during patient transport may lead to casualty morbidity. Percent systolic pressure variation (%SPV) is one of several technologies that perform a dynamic assessment of fluid responsiveness (FT-DYN). Trained anesthesia providers can visually estimate and use %SPV to limit the incidence of erroneous volume management decisions to 1-4%. However, the accuracy of visually estimated %SPV by other specialties is unknown. The aim of this article is to determine the accuracy of estimated %SPV and the incidence of erroneous volume management decisions for Critical Care Air Transport (CCAT) team members before and after training to visually estimate and utilize %SPV. MATERIAL AND METHODS: In one sitting, CCAT team providers received didactics defining %SPV and indicators of fluid responsiveness and treatment with %SPV ≤7 and ≥14.5 defining a fluid nonresponsive and responsive patient, respectively; they were then shown ten 45-second training arterial waveforms on a simulated Propaq M portable monitor's screen. Study subjects were asked to visually estimate %SPV for each arterial waveform and queried whether they would treat with a fluid bolus. After each training simulation, they were told the true %SPV. Seven days post-training, the subjects were shown a different set of ten 45-second testing simulations and asked to estimate %SPV and choose to treat, or not. Nonparametric limits of agreement for differences between true and estimated %SPV were analyzed using Bland-Altman graphs. In addition, three errors were defined: (1) %SPV visual estimate errors that would label a volume responsive patient as nonresponsive, or vice versa; (2) incorrect treatment decisions based on estimated %SPV (algorithm application errors); and (3) incorrect treatment decisions based on true %SPV (clinically significant treatment errors). For the training and testing simulations, these error rates were compared between, and within, provider groups. RESULTS: Sixty-one physicians (MDs), 64 registered nurses (RNs), and 53 respiratory technicians (RTs) participated in the study. For testing simulations, the incidence and 95% CI for %SPV estimate errors with sufficient magnitude to result in a treatment error were 1.4% (0.5%, 3.2%), 1.6% (0.6%, 3.4%), and 4.1% (2.2%, 6.9%) for MDs, RNs, and RTs, respectively. However, clinically significant treatment errors were statistically more common for all provider types, occurring at a rate of 7%, 10%, and 23% (all P < .05). Finally, students did not show clinically relevant reductions in their errors between training and testing simulations. CONCLUSIONS: Although most practitioners correctly visually estimated %SPV and all students completed the training in interpreting and applying %SPV, all groups persisted in making clinically significant treatment errors with moderate to high frequency. This suggests that the treatment errors were more often driven by misapplying FT-DYN algorithms rather than by inaccurate visual estimation of %SPV. Furthermore, these errors were not responsive to training, suggesting that a decision-making cognitive aid may improve CCAT teams' ability to apply FT-DYN technologies.

Synthesis of 1,3-diphenyl-6-alkyl/aryl-substituted fulvene chromophores: observation of π-π interactions in a 6-pyrene-substituted 1,3-diphenylfulvene.

The synthesis, structural, and electronic properties of nine 1,3-diphenyl-6-alkyl/aryl substituted pentafulvenes were studied. Pyrene ring π-π interactions were revealed from analysis of the experimental crystal packing of 1,3-diphenyl-6-(1-pyrene)fulvene and supporting DFT calculations. Photophysical properties derived from UV-vis and fluorescence emission measurements demonstrated tunable and low HOMO-LUMO band gaps for the series. The presented results point to a model synthetic approach for incorporation of extended π systems and donor-π-acceptor groups for fulvene-based electronic materials.

Hospital-Acquired Condition Rate of Admitting Facility Does Not Predict Mortality in Traumatically Injured Patients.

BACKGROUND: Hospital-acquired conditions (HACs) are increasingly scrutinized as markers of hospital quality and are subject to increasing regulatory and financial pressure. Despite this, there is little evidence that HACs are associated with poor outcomes in traumatically injured patients, or that lower HAC rates are a marker of a better quality of care. Our study compares mortality rates in hospitals with high versus low rates of HAC. Our hypothesis is that high HAC trauma centers have higher mortality. METHODS: The latest editions of the National Trauma Data Bank (NTDB) containing facility identification keys (2011 to 2015) were combined. The HACs targeted by the Centers for Medicare and Medicaid Services (CMS) Hospital-Acquired Condition Reduction Program (HACRP) were identified. Hospital-acquired conditions per 1000 patient-days were calculated for individual trauma centers, and these facilities were stratified into quartiles by HAC rate. Propensity score matching was used to match patients admitted to hospitals in the highest versus the lowest quartiles. RESULTS: Complete data was available for 3,510,818 patients; 58,296 (1.67%) developed HACs recorded in the NTDB. Good performing centers had a mean of 0.84 HACs per 1000 patient-days compared to 7.82 at poor-performing centers. After propensity matching, patients treated at good performing centers had higher mortality of 1.22% versus 1.02% at poor-performing centers (p<0.001). The facility characteristics most over-represented in the poor performing quartile were: University (45.19% vs 10.59%, p<0.001), American College of Surgeons (ACS) Level I Status (31.85% vs 2.24%, p<0.001), and bed size > 600 (28.15% vs 5.5%, p<0.001). CONCLUSION: Injured patients treated at poor-performing centers (high HAC) have reduced mortality relative to good performing centers (low HAC). Large academic centers were overwhelmingly represented in the poor-performing quartile. Hospital-acquired conditions may be markers of a non-modifiable underlying patient and facility characteristics rather than markers of poor hospital quality.

Recurrence risk of villitis of unknown etiology: Analysis of a large retrospective cohort study, systematic review and meta-analysis.

INTRODUCTION: Recurrence risk of villitis of unknown etiology (VUE) remains uncertain because of few studies and their methodologic limitations. We calculated recurrence risk in a large population of deliveries after minimizing important biases and compared it to others via systematic review and meta-analysis. METHODS: Over 11 years of placenta pathology reports on singleton deliveries were retrieved and searched for 'villitis' or 'VUE'. Cases of acute villitis and chronic villitis from infections were eliminated via pathologist review. Reports were merged to data containing gestational age, parity and gravida. Recurrence risk of VUE per patient, per parity and per gravida was determined among patients with ≥2 placentas examined for deliveries ≥20 weeks gestation. Results were compared to those from articles and their references identified by a MEDLINE® search. Recurrence risks among methodologically similar studies were pooled using a random effects model. RESULTS: Among 29 124 placenta pathology reports from 27 087 patients, there were 2423 cases of VUE among 2382 patients, of which 153 had ≥2 placentas examined. There were 41 recurrent cases of VUE for a recurrence risk of 27% per patient, 22% per parity, and 19% per gravida. We identified 64 articles, of which 4 were retained. One examined all placentas from all births over a ∼3-year period, finding a recurrence risk of 27%. The remaining 3 studies, along with our own, used indications for placental examination and had a pooled recurrence risk of 30% (95% Confidence Interval: 0.21-0.41). DISCUSSION: In our study, which is the largest, most comprehensive, and methodologically robust to date, VUE recurrence risk was ∼30%.

In-hospital mortality in acute ischemic stroke treated with hemicraniectomy in US hospitals.

Hemicraniectomy is a surgical procedure performed to prevent cerebral herniation and death in patients who have sustained a massive ischemic stroke in the anterior circulation territory. Information on in-hospital mortality in patients with large ischemic stroke treated with hemicraniectomy outside randomized trials is lacking. We sought to identify in-hospital mortality associated with hemicraniectomy in a large US sample. We selected our cohort from the National Inpatient Sample database for the years 2000 through 2006 using the clinical classification software codes for acute ischemic stroke (AIS) and arterial occlusion, and identified those patients treated with thrombolysis or hemicraniectomy by the procedure codes. A multivariate logistic regression model was used for adjusted analysis. Among 502,231 patients with AIS, 252 (0.05%) underwent hemicraniectomy, and 7526 (1.5%) were treated with thrombolysis. Compared with the nonsurgical group, patients treated with hemicraniectomy were younger (mean age, 55.6 vs 71.5 years) and had lower Charlson Comorbidity Index scores (92.8% vs 76.0%). The mortality rate was higher in the hemicraniectomy group (32.1% vs 10.8%; adjusted odds ratio [OR] = 3.91; 95% confidence interval [CI] = 2.97-5.16). In patients treated with thrombolysis, mortality was higher in the hemicraniectomy group compared with the nonsurgical group (35.3% vs 13.1%; P = .01). The rate of hospital utilization of hemicraniectomy varied between 0.04% and 0.06% among all stroke admissions; the trend did not change significantly over the 7-year study period (P = .06). The mortality rate in hemicraniectomy-treated patients was significantly lower than in historical cohorts however, hemicraniectomy remains associated with high in-hospital mortality. The rate of utilization of hemicraniectomy for AIS in US hospitals has remained essentially unchanged.