Effects of Liqi Tongbian decoction on gut microbiota, SCFAs production, and 5-HT pathway in STC rats with Qi Stagnation Pattern.

Slow transit constipation (STC) is a common and debilitating condition characterized by delayed colonic transit and difficulty in fecal expulsion, significantly impacting patients' physical and mental wellbeing as well as their overall quality of life. This study investigates the therapeutic potential of Liqi Tongbian Decoction (LTD) in the treatment of STC, especially in cases involving the context of Qi stagnation, through a multifaceted approach involving the modulation of intestinal flora and short-chain fatty acids (SCFAs). We employed a rat model of STC with Qi Stagnation Pattern, established using the "loperamide + tail-clamping provocation method," to explore the effects of LTD on fecal characteristics, intestinal motility, and colonic pathology. Importantly, LTD exhibited the ability to increase the richness, diversity, and homogeneity of intestinal flora while also modulating the composition of microorganisms. It significantly increased the production of SCFAs, especially butyric acid. Moreover, LTD exerted a substantial influence on the synthesis of serotonin (5-HT) by modulating the expression of tryptophan hydroxylase (TPH) and interacting with the 5-HT4 receptor (5-HT4R), resulting in enhanced colonic motility. Correlation analyses revealed a positive correlation between certain bacterial genera, such as Lachnospiraceae_NK4A136 spp. and Clostridiales spp. and the concentrations of butyric acid and 5-HT. These results suggest a mechanistic link between microbiome composition, SCFAs production, and 5-HT synthesis. These findings highlight the potential of LTD to alleviate STC by facilitating a beneficial interplay among intestinal flora, SCFAs production, and 5-HT-mediated colonic motility, providing novel insights into the management of STC with Qi Stagnation Pattern.

National pilot of entrustable professional activities in pathology residency training.

Entrustable professional activities (EPAs) are observable clinical skills and/or procedures that have been introduced into medical education at the student and resident levels in most specialties to determine readiness to advance into residency or independent practice, respectively. This publication describes the process and outcomes of a pilot study looking at the feasibility of using two anatomic pathology and two clinical pathology EPAs in pathology residency in 6 pathology residency programs that volunteered for the study. Faculty development on EPAs and their assessment was provided to pilot program faculty, and EPA assessment tools were developed and used by the pilot programs. Pre- and post-study surveys were given to participating residents, faculty, and program directors to gauge baseline practices and to gather feedback on the EPA implementation experience. Results demonstrated overall good feasibility in implementing EPAs. Faculty acceptance of EPAs varied and was less than that of program directors. Residents reported a significant increase in the frequency with which faculty provided formative assessments that included specific examples of performance and specific ways to improve, as well as increased frequency with which faculty provided summative assessments that included specific ways to improve. EPAs offered the most benefit in setting clear expectations for performance of each task, for providing more specific feedback to residents, and in increasing Program director's understanding of resident strengths abilities and weaknesses.

Accuracy of augmented reality-guided needle placement for pulsed radiofrequency treatment of pudendal neuralgia: a pilot study on a phantom model.

Background: Pudendal neuralgia (PN) is a chronic neuropathy that causes pain, numbness, and dysfunction in the pelvic region. The current state-of-the-art treatment is pulsed radiofrequency (PRF) in which a needle is supposed to be placed close to the pudendal nerve for neuromodulation. Given the effective range of PRF of 5 mm, the accuracy of needle placement is important. This study aimed to investigate the potential of augmented reality guidance for improving the accuracy of needle placement in pulsed radiofrequency treatment for pudendal neuralgia. Methods: In this pilot study, eight subjects performed needle placements onto an in-house developed phantom model of the pelvis using AR guidance. AR guidance is provided using an in-house developed application on the HoloLens 2. The accuracy of needle placement was calculated based on the virtual 3D models of the needle and targeted phantom nerve, derived from CBCT scans. Results: The median Euclidean distance between the tip of the needle and the target is found to be 4.37 (IQR 5.16) mm, the median lateral distance is 3.25 (IQR 4.62) mm and the median depth distance is 1.94 (IQR 7.07) mm. Conclusion: In this study, the first method is described in which the accuracy of patient-specific needle placement using AR guidance is determined. This method could potentially improve the accuracy of PRF needle placement for pudendal neuralgia, resulting in improved treatment outcomes.

Effects of long-term exposure to outdoor air pollution on COVID-19 incidence: A population-based cohort study accounting for SARS-CoV-2 exposure levels in the Netherlands.

Several studies have linked air pollution to COVID-19 morbidity and severity. However, these studies do not account for exposure levels to SARS-CoV-2, nor for different sources of air pollution. We analyzed individual-level data for 8.3 million adults in the Netherlands to assess associations between long-term exposure to ambient air pollution and SARS-CoV-2 infection (i.e., positive test) and COVID-19 hospitalisation risks, accounting for spatiotemporal variation in SARS-CoV-2 exposure levels during the first two major epidemic waves (February 2020-February 2021). We estimated average annual concentrations of PM10, PM2.5 and NO2 at residential addresses, overall and by PM source (road traffic, industry, livestock, other agricultural sources, foreign sources, other Dutch sources), at 1 × 1 km resolution, and weekly SARS-CoV-2 exposure at municipal level. Using generalized additive models, we performed interval-censored survival analyses to assess associations between individuals' average exposure to PM10, PM2.5 and NO2 in the three years before the pandemic (2017-2019) and COVID-19-outcomes, adjusting for SARS-CoV-2 exposure, individual and area-specific confounders. In single-pollutant models, per interquartile (IQR) increase in exposure, PM10 was associated with 7% increased infection risk and 16% increased hospitalisation risk, PM2.5 with 8% increased infection risk and 18% increased hospitalisation risk, and NO2 with 3% increased infection risk and 11% increased hospitalisation risk. Bi-pollutant models suggested that effects were mainly driven by PM. Associations for PM were confirmed when stratifying by urbanization degree, epidemic wave and testing policy. All emission sources of PM, except industry, showed adverse effects on both outcomes. Livestock showed the most detrimental effects per unit exposure, whereas road traffic affected severity (hospitalisation) more than infection risk. This study shows that long-term exposure to air pollution increases both SARS-CoV-2 infection and COVID-19 hospitalisation risks, even after controlling for SARS-CoV-2 exposure levels, and that PM may have differential effects on these COVID-19 outcomes depending on the emission source.

Radioactive iodine administration is not associated with improved disease-specific survival in classic papillary thyroid carcinoma greater than 4 cm confined to the thyroid.

BACKGROUND: We aimed to evaluate the impact of radioactive iodine on disease-specific survival in intrathyroidal (N0M0) papillary thyroid carcinoma >4 cm, given conflicting data in the American Thyroid Association guidelines regarding their management. METHODS: The Surveillance, Epidemiology, and End Results database was queried for N0M0 classic papillary thyroid carcinoma >4 cm. Kaplan-Meier estimates were performed to compare disease-specific survival between radioactive iodine-treated and untreated groups. A multivariable Cox regression was performed to identify predictors of disease-specific survival. RESULTS: There were more patients aged ≥55 (41.7% vs 32.3%, P = .001) and fewer multifocal tumors (25.3% vs 30.6%, P = .006) in the no radioactive iodine group. Ten-year disease-specific survival was similar between the radioactive iodine treated and untreated groups (97.2% vs 95.6%, P = .34). Radioactive iodine was not associated with a significant disease-specific survival benefit (adjusted hazard ratio = 0.78, confidence interval [0.39-1.58], P = .49). Age ≥55 (adjusted hazard ratio = 3.50, confidence interval [1.69-7.26], P = .001) and larger tumor size (adjusted hazard ratio = 1.04, confidence interval [1.02-1.06], P < .001) were associated with an increased risk of disease-specific death. Subgroup analyses did not demonstrate improved disease-specific survival with radioactive iodine in patients ≥55 and in tumors >5 cm. CONCLUSION: Adjuvant radioactive iodine administration in classic papillary thyroid carcinoma >4 cm confined to the thyroid did not significantly impact disease-specific survival. Thus, these patients may not require routine treatment with adjuvant radioactive iodine.

Adjuvant treatment with S-1 in patients after R0-resection of adenocarcinoma of the stomach and esophagogastric junction - A multicenter phase I/II feasibility study (GMBH-STO-0114).

INTRODUCTION: S-1 has been shown to be an effective adjuvant treatment option for East Asian patients who underwent gastrectomy for stage II/III gastric cancer. We conducted a phase I/II study to evaluate the feasibility, tolerability and efficacy of administering S-1 in the adjuvant setting after R0-resection of adenocarcinoma of the stomach and esophagogastric junction (EGJ) in Caucasian patients. METHODS: In this single-cohort, open-label, phase I/II trial, we enrolled patients with locally advanced adenocarcinoma of the stomach or EGJ having undergone R0-resection with or without neoadjuvant treatment. One treatment cycle consisted of oral S-1 (30mg/m² bid) for 14 days. Cycles were repeated every 3 weeks for 18 cycles (54 weeks). Primary endpoint was feasibility and tolerability. Safety was evaluated according to the common toxicity criteria adverse events 4.0 criteria. Secondary endpoints were one-year relapse-free survival rate, relapse-free survival (RFS) and overall survival (OS). RESULTS: Between 10/2015 and 02/2018, 32 patients were enrolled in 12 German centres and 30 started adjuvant study treatment. Seventeen patients completed all 18 cycles. Two patients terminated study treatment due to adverse events (AEs), 7 due to patient's or investigator's decision and 4 due to recurrence or distant metastasis during adjuvant therapy. Dose levels were reduced to 25 mg/m² in 9 patients, and to 20 mg/m² in 1 patient. Of patients completing all 18 cycles, 5 did so with reduced dosage of S-1. Documented grade ≥ 3 AEs were neutropenia, diarrhoea, vomiting, polyneuropathy, palmar-plantar erythrodysaesthesia and rash. Serious AEs were observed in 7 patients. Median RFS was 32.2 months. One-year relapse-free survival rate was 77%. Data on OS were still premature at the end of the study. CONCLUSION: Adjuvant treatment with S-1 for one year is a feasible and safe treatment option for Caucasian patients diagnosed with gastric adenocarcinoma or cancer of the EGJ cancer after R0-resection.

Estimating the Potential Public Health Value of BCG Revaccination.

An upcoming trial may provide further evidence that adolescent/adult-targeted BCG revaccination prevents sustained Mycobacterium tuberculosis infection, but its public health value depends on its impact on overall tuberculosis morbidity and mortality, which will remain unknown. Using previously calibrated models for India and South Africa, we simulated BCG revaccination assuming 45% prevention-of-infection efficacy, and we evaluated scenarios varying additional prevention-of-disease efficacy between +50% (reducing risk) and -50% (increasing risk). Given the assumed prevention-of-infection efficacy and range in prevention-of-disease efficacy, BCG revaccination may have a positive health impact and be cost-effective. This may be useful when considering future evaluations and implementation of adolescent/adult BCG revaccination.

[Clinical aspects and treatment of tricuspid valve regurgitation]. / Klinik und Therapie der Trikuspidalklappeninsuffizienz.

Tricuspid regurgitation (TR) leading to right heart failure is prevalent and associated with increased mortality. The significant under-recognition of the disease resulted from insufficient medical therapies and the high associated risk of surgical therapy. Over the last decade there has been a rapid development of interventional treatment options so that the disease has increasingly become the focus of attention of specialists in internal medicine and interventional cardiologists. The etiology of TR is differentiated into primary TR, secondary atrial TR, secondary ventricular TR and TR associated with cardiac implantable electronic devices (CIED). The TR was identified as an independent predictor of mortality, independent of associated diseases such as atrial fibrillation, left-sided heart failure or pulmonary hypertension. Even patients with low to moderate TR have a significantly increased risk of mortality. Early diagnostics and estimation of the severity by echocardiography as well as timely referral to a tertiary heart valve center are decisive in order to evaluate possible treatment options before irreversible right ventricular damage and secondary organ dysfunction occur. For transcatheter edge-to-edge repair and transcatheter tricuspid valve replacement there is now first evidence from randomized controlled studies. While the understanding of TR is continuously improving, new tricuspid valve repair and replacement systems are in a state of steady progress. Whether the treatment has an effect on reduction of the mortality and stabilization of right ventricular failure with a reduction in hospitalization, will first be shown in future studies.

Minimizing Nipple-Areolar Complex Complications in Prepectoral Breast Reconstruction After Nipple-Sparing Mastectomy.

PURPOSE: Nipple-areolar complex (NAC) viability remains a significant concern following prepectoral tissue expander (TE) reconstruction after nipple-sparing mastectomy (NSM). This study assesses the impact of intraoperative TE fill on NAC necrosis and identifies strategies for mitigating this risk. METHODS: A chart review of all consecutive, prepectoral TEs placed immediately after NSM was performed between March 2017 and December 2022 at a single center. Demographics, mastectomy weight, intraoperative TE fill, and complications were extracted for all patients. Partial NAC necrosis was defined as any thickness of skin loss including part of the NAC, whereas total NAC necrosis was defined as full-thickness skin loss involving the entirety of the NAC. P < 0.05 was considered statistically significant. RESULTS: Forty-six patients (83 breasts) with an average follow-up of 22 months were included. Women were on average 46 years old, nonsmoker (98%), and nondiabetic (100%) and had a body mass index of 23 kg/m2. All reconstructions were performed immediately following prophylactic mastectomies in 49% and therapeutic mastectomies in 51% of cases. Three breasts (4%) were radiated, and 15 patients (33%) received chemotherapy. Mean mastectomy weight was 346 ± 274 g, median intraoperative TE fill was 150 ± 225 mL, and median final TE fill was 350 ± 170 mL. Partial NAC necrosis occurred in 7 breasts (8%), and there were zero instances of complete NAC necrosis. On univariate analysis, partial NAC necrosis was not associated with any patient demographic or operative characteristics, including intraoperative TE fill. In multivariable models controlling for age, body mass index, mastectomy weight, prior breast surgery, and intraoperative TE fill, partial NAC necrosis was associated with lower body mass index (odds ratio, 0.53; confidence interval [CI], 0.29-0.98; P < 0.05) and higher mastectomy weight (odds ratio, 1.1; CI, 1.01-1.20; P < 0.05). Prior breast surgery approached significance, as those breasts had a 19.4 times higher odds of partial NAC necrosis (95% CI, 0.88-427.6; P = 0.06). CONCLUSIONS: Nipple-areolar complex necrosis following prepectoral TE reconstruction is a rare but serious complication. In this study of 83 breasts, 7 (8%) developed partial NAC necrosis, and all but one were able to be salvaged.

Estimating migration timing and abundance in partial migratory systems by integrating continuous antenna detections with physical captures.

Many populations migrate between two different habitats (e.g. wintering/foraging to breeding area, mainstem-tributary, river-lake, river-ocean, river-side channel) as part of their life history. Detection technologies, such as passive integrated transponder (PIT) antennas or sonic receivers, can be placed at boundaries between habitats (e.g. near the confluence of rivers) to detect migratory movements of marked animals. Often, these detection systems have high detection probabilities and detect many individuals but are limited in their ability to make inferences about abundance because only marked individuals can be detected. Here, we introduce a mark-recapture modelling approach that uses detections from a double-array PIT antenna system to imply movement directionality from arrays and estimate migration timing. Additionally, when combined with physical captures, the model can be used to estimate abundances for both migratory and non-migratory groups and help quantify partial migration. We first test our approach using simulation, and results indicate our approach displayed negligible bias for total abundance (less than ±1%) and slight biases for state-specific abundance estimates (±1%-6%). We fit our model to array detections and physical captures of three native fishes (humpback chub [Gila cypha], flannelmouth sucker [Catostomus latipinnis] and bluehead sucker [Catostomus discobolus]) in the Little Colorado River (LCR) in Grand Canyon, AZ, a system that exhibits partial migration (i.e. includes residents and migrants). Abundance estimates from our model confirm that, for all three species, migratory individuals are much more numerous than residents. There was little difference in movement timing between 2021 (a year without preceding winter/spring floods) and 2022 (a year with a small flood occurring in early April). In both years, flannelmouth sucker arrived in mid-March whereas humpback chub and bluehead sucker arrivals occurred early- to mid-April. With humpback chub and flannelmouth sucker, movement timing was influenced by body size so that large individuals were more likely to arrive early compared to smaller individuals. With more years of data, this model framework could be used to evaluate ecological questions pertaining to flow cues and movement timing or intensity, relative trends in migrants versus residents and ecological drivers of skipped spawning.

Antimicrobial Resistance Profiles of Campylobacter spp. Recovered from Chicken Farms in Two Districts of Bangladesh.

The rapid emergence of antimicrobial resistance (AMR) in Campylobacter has reinforced its status as a foodborne pathogen of significant public health concern. Resistant Campylobacter is typically transferred to humans via the consumption of contaminated animal products, particularly poultry. The genes associated with antimicrobial resistance in Campylobacter spp. are poorly understood. To address this knowledge gap, we conducted a prevalence survey of AMR Campylobacter across 84 chicken farms in two districts of Bangladesh. Pooled cloacal swabs were collected from chickens and underwent bacteriological testing for Campylobacter spp. with PCR confirmation. Antimicrobial susceptibility was tested against 14 antibiotics by disk diffusion method, and 12 resistance genes were screened in Campylobacter-positive isolates using multiplex PCR. A total of 34 (40.5%) farms were Campylobacter-positive of which 73.5% of isolates were resistant to at least 10 antibiotics. The antimicrobial susceptibility results indicate a high level of resistance against streptomycin (97.1%), clindamycin (97.1%), ampicillin (94.1%), tetracycline (94.1%), erythromycin (91.2%), ciprofloxacin (88.2%), nalidixic acid (85.3%), and imipenem (82.4%), and comparatively a low frequency of resistance to chloramphenicol (47.1%), ceftazidime (44.1%), and colistin (35.3%). Multidrug-resistant (MDR) and extensively drug-resistant Campylobacter were identified in 97.1%, and 50% of isolates, respectively. Ten resistance genes were identified including blaTEM (in 97.1% of isolates), strA-strB (85.9%), tetA (70.6%), tetB (32.4%), qnrS (23.5%), blaCTX-M-1 (20.6%), qnrB (20.6%), blaSHV (8.8%), aadB (5.9%), and qnrA (2.9%). Our findings demonstrate that resistance to ampicillin, tetracycline, and ceftazidime in Campylobacter isolates was significantly (p ≤ 0.05) associated with the presence of blaTEM, tetA, and blaSHV genes, respectively. The high rates of AMR in Campylobacter isolates from our study are not surprising given the liberal use of antimicrobials and incomplete biosecurity provisions on farms. Of particular concern are resistance rates to those classes of antibiotics that should be reserved for human use (azithromycin, ciprofloxacin, and colistin). AMR was more prevalent in chicken farms that used multiple antibiotics, engaged in prophylactic treatment of the birds, and improperly disposed of antibiotic packages. The high prevalence of MDR in chicken-derived Campylobacter isolates from the different regions of our study reinforces the need for more prudent use of antimicrobial compounds in Bangladeshi chicken farms.

Results of an interlaboratory study on the working curve in vat photopolymerization.

The working curve informs resin properties and print parameters for stereolithography, digital light processing, and other photopolymer additive manufacturing (PAM) technologies. First demonstrated in 1992, the working curve measurement of cure depth vs radiant exposure of light is now a foundational measurement in the field of PAM. Despite its widespread use in industry and academia, there is no formal method or procedure for performing the working curve measurement, raising questions about the utility of reported working curve parameters. Here, an interlaboratory study (ILS) is described in which 24 individual laboratories performed a working curve measurement on an aliquot from a single batch of PAM resin. The ILS reveals that there is enormous scatter in the working curve data and the key fit parameters derived from it. The measured depth of light penetration Dp varied by as much as 7x between participants, while the critical radiant exposure for gelation Ec varied by as much as 70x. This significant scatter is attributed to a lack of common procedure, variation in light engines, epistemic uncertainties from the Jacobs equation, and the use of measurement tools with insufficient precision. The ILS findings highlight an urgent need for procedural standardization and better hardware characterization in this rapidly growing field.

Inflammatory and tissue injury marker dynamics in pediatric acute respiratory distress syndrome.

BACKGROUND: The molecular signature of pediatric acute respiratory distress syndrome (ARDS) is poorly described, and the degree to which hyperinflammation or specific tissue injury contributes to outcomes is unknown. Therefore, we profiled inflammation and tissue injury dynamics over the first 7 days of ARDS, and associated specific biomarkers with mortality, persistent ARDS, and persistent multiple organ dysfunction syndrome (MODS). METHODS: In a single-center prospective cohort of intubated pediatric ARDS, we collected plasma on days 0, 3, and 7. Nineteen biomarkers reflecting inflammation, tissue injury, and damage associated molecular patterns were measured. We assessed the relationship between biomarkers and trajectories with mortality, persistent ARDS, or persistent MODS using multivariable mixed effect models. RESULTS: In 279 subjects (64 [23%] non-survivors), hyperinflammatory cytokines, tissue injury markers, and DAMPs were higher in non-survivors. Survivors and non-survivors showed different biomarker trajectories. IL-1α, sTNFR1, ANG2, and SPD increased in non-survivors, while DAMPs remained persistently elevated. ANG2 and P3NP were associated with persistent ARDS, whereas multiple cytokines, tissue injury markers, and DAMPs were associated with persistent MODS. Corticosteroid use did not impact the association of biomarker levels or trajectory with mortality. CONCLUSIONS: Pediatric ARDS survivors and non-survivors had distinct biomarker trajectories, with cytokines, endothelial and alveolar epithelial injury, and DAMPs elevated in non-survivors. Mortality markers overlapped with markers associated with persistent MODS, rather than persistent ARDS.

Effect of tobacco use on Zenker's diverticulotomy outcomes.

OBJECTIVE: To compare clinical outcomes in patients with and without history of tobacco use who underwent Zenker's diverticulotomy (ZD). STUDY DESIGN: Single institution retrospective review. SETTING: Tertiary care academic hospital. METHODS: A retrospective review of patients who underwent ZD via an open stapler, rigid endoscopic CO2 laser, stapler or harmonic scalpel, and flexible endoscopic technique from January 2006 to December 2020 was performed. Data were abstracted for patient demographics, diverticular features, and rates of adverse events and symptomatic recurrence. RESULTS: Out of 424 patients, 146 (34.4 %) had a history of tobacco use: 126 (29.7 %) were former smokers, and 20 (4.7 %) were active smokers. In univariable cross-sectional analyses, the likelihood of postoperative bleeding, perforation, emergency department visits, unplanned readmission, or recurrence did not demonstrate an association with tobacco use history even after adjustment for age, sex, and surgical approach. Similarly, in Cox Proportional Hazards regression, tobacco use was not associated with an increased risk of recurrence, even after correcting for age, sex, and type of surgery. The median time to recurrence observed in our cohort was 11.5 years amongst non-smokers, 8.7 years amongst former smokers, and 1.2 years amongst active smokers (p = 0.94). CONCLUSIONS: There were no significant differences in post-operative adverse events or frequency of recurrence of ZD between active, former, and non-smokers. Although underpowered and not statistically significant, median time to recurrence appears to be shorter in smokers when compared with former and non-smokers following surgery.

Neuropathologic changes at age 90+ related to sleep duration 19 to 40 years earlier: The 90+ Study.

INTRODUCTION: We investigated the association between sleep duration and neuropathologic changes 19 to 40 years later in oldest-old (age 90+) participants of The 90+ Study. METHODS: Participants self-reported sleep duration and underwent neuropathologic evaluation. We categorized sleep duration as < 7, 7 to 8 = reference, > 8 hours and dichotomized neuropathologic changes as present/absent. We estimated odds ratio (OR) and 95% confidence intervals (CI) using logistic regression. RESULTS: In 264 participants, mean age at sleep self-report was 69 years, mean age at autopsy was 98 years, and mean interval between sleep self-report and autopsy was 29 years (range: 19-40). Those reporting > 8 hours of sleep had lower likelihood of limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) inclusions (OR = 0.18; CI = 0.04-0.82) and amyloid beta deposits (OR = 0.34; 95% CI = 0.12-0.94). DISCUSSION: Long self-reported sleep is associated with lower odds of neurodegenerative neuropathologic changes 19 to 40 years later in the oldest-old, suggesting a potential role of sleep in accumulation of dementia-related neuropathologies. HIGHLIGHTS: Association of self-reported sleep with non-Alzheimer's disease neuropathologic changes has not been explored. Whether sleep duration is related to dementia neuropathologic changes decades later is unclear. Long self-reported sleep is associated with lower odds of Alzheimer's disease neuropathologic change 19 to 40 years later in the oldest-old. Long self-reported sleep is associated with lower odds of limbic-predominant age-related TDP-43 encephalopathy neuropathologic change 19 to 40 years later in the oldest-old.

A Single Hospital-Wide Antibiogram is Insufficient to Account for Differences in Antibiotic Resistance Patterns Across Multiple ICUs.

BACKGROUND: Infection is a common cause of mortality within intensive care units (ICUs). Antibiotic resistance patterns and culture data are used to create antibiograms. Knowledge of antibiograms facilitates guiding empiric therapies and reduces mortality. Most major hospitals utilize data collection to create hospital-wide antibiograms. Previous studies have shown significant differences in susceptibility patterns between hospital wards and ICUs. We hypothesize that institutional or combined ICU antibiograms are inadequate to account for differences in susceptibility for patients in individual ICUs. METHODS: Culture and susceptibility data were reviewed over a 1-year period for 13 bacteria in the following ICUs: Surgical/Trauma, Medical, Neuroscience, Burn, and Emergency department. Antibiotic management decisions are made by individual teams. RESULTS: Nine species had sufficient data for inclusion into an All-ICU antibiogram. E coli and S aureus were the most common isolates. Seven species had significant differences in susceptibility patterns between ICUs. E cloacae showed higher rates of resistance to multiple antibiotics in the STICU than other ICUs. P aeruginosa susceptibility rates in the NSICU and BICU were 88% and 92%, respectively, compared to 60% and 55% in the STICU and MICU. Cephalosporins and Aztreonam had reduced efficacy against E coli in the NSICU, however remain effective in other ICUs. CONCLUSIONS: The results of this study show that different ICUs do have variability in antibiotic susceptibility patterns within a single hospital. While this only represents a single institution, it shows that the use of hospital-wide antibiograms is inadequate for creating empiric antibiotic protocols within individual ICUs.

Effect of CSL112 on Recurrent Myocardial Infarction and Cardiovascular Death: Insights from the AEGIS-II Trial.

BACKGROUND: The AEGIS-II trial hypothesized that CSL112, an intravenous formulation of human apoA-I, would lower the risk of plaque disruption, decreasing the risk of recurrent events such as myocardial infarction (MI) among high-risk patients with MI. OBJECTIVES: This exploratory analysis evaluates the effect of CSL112 therapy on the incidence of CV death and recurrent MI. METHODS: The AEGIS-II trial was an international, multicenter, randomized, double-blind, placebo-controlled trial that randomized 18,219 high-risk acute MI patients to 4 weekly infusions of apoA-I (6g CSL112) or placebo. RESULTS: The incidence of the composite of cardiovascular death and type 1 MI was 11-16% lower in the CSL112 group over the study period (HR of 0.84 [95% CI 0.7-1.0; p=0.056] day 90, HR 0.86, [95% CI 0.74-0.99; p=0.048] day 180, and HR 0.89, [95% CI 0.79-1.01 p=0.07; p=0.07] day 365). Similarly, the incidence of CV death or any MI was numerically lower in CSL112 treated patients throughout the follow-up period (HR 0.92 [95% CI 0.8-1.05], 0.89 [95% CI 0.79-0.996], 0.91 [0.82-1.01]. The effect of CSL112 treatment on MI was predominantly observed for type 1 MI and type 4b (MI due to stent thrombosis). CONCLUSION: While CSL112 did not significantly reduce the occurrence of the primary study endpoints, patients treated with CSL112 infusions had numerically lower rates of CV death and MI, type-1 MI, and stent thrombosis-related MI compared to placebo. These findings could suggest a role of apoA-I in reducing subsequent plaque disruption events via enhanced cholesterol efflux. Further prospective data would be needed to confirm these observations.

An effective method for preparing histological sections of blow fly intra-puparial stages for minimum PMI estimations.

Blow flies (Diptera: Calliphoridae) are generally early colonisers of fresh cadavers, enabling the estimation of a minimum post-mortem interval (minPMI) based on an accurate aging of the oldest immature stages associated with a cadaver. In blow flies, the pupal stage and the subsequent development of the adult take place inside a protective case, the puparium, formed from the hardened and darkened cuticle of the third instar larva. Because the puparium is an opaque structure that shows virtually no external changes, qualitative analyses of the internal tissues can be very informative for determining reliable age-specific morphological markers. Those analyses can be performed using either non-invasive but expensive and not widely accessible techniques, or traditional histological methods, which are invasive as they require the serial sectioning of the sample. Histological methods are often readily available for forensic researchers and practitioners; however, the histological study of blow fly intra-puparial stages has traditionally been hampered by the poor paraffin infiltration of tissues due to the abundance of fat bodies, resulting in usually fragmented sections and the subsequent loss of relevant information. We present here an effective method for the preparation of histological sections of blow fly intra-puparial stages, maximising the paraffin infiltration while enabling the production of clean and entire sections that allow for the use of reliable age-specific morphological markers, thus improving the accuracy of minPMI estimations when access to more costly techniques is not feasible.

Cost Savings of Whole Blood Versus Component Therapy at a Community Level 1 Trauma Center.

BACKGROUND: Blood product component-only resuscitation (CORe) has been the standard of practice in both military and civilian trauma care with a 1:1:1 ratio used in attempt to recreate whole blood (WB) until recent data demonstrated WB to confer a survival advantage, leading to the emergence of WB as the contemporary resuscitation strategy of choice. Little is known about the cost and waste reduction associated with WB vs CORe. METHODS: This study is a retrospective single-center review of adult trauma patients admitted to a community trauma center who received WB or CORe as part of their massive transfusion protocol (MTP) resuscitation from 2017 to 2021. The WB group received a minimum of one unit WB while CORe received no WB. Univariate and multivariate analyses were completed. Statistical analysis was conducted using a 95% confidence level. Non-normally distributed, continuous data were analyzed using the Wilcoxon rank sum test. RESULTS: 576 patients were included (201 in WB and 375 in CORe). Whole blood conveyed a survival benefit vs CORe (OR 1.49 P < .05, 1.02-2.17). Whole blood use resulted in an overall reduction in products prepared (25.8%), volumes transfused (16.5%), product waste (38.7%), and MTP activation (56.3%). Cost savings were $849 923 annually and $3 399 693 over the study period. DISCUSSION: Despite increased patient volumes over the study period (43.7%), the utilization of WB as compared to CORe resulted in an overall $3.39 million cost savings while improving mortality. As such, we propose WB should be utilized in all resuscitation strategies for the exsanguinating trauma patient.