Local Control of Pyoderma Gangrenosum Using Human Amniotic Membrane and Transcriptome Analysis.

Pyoderma gangrenosum (PG) is a rare, chronic, ulcerative disease characterized by non-healing wounds that worsen with debridement, a phenomenon called pathergy. No consensus regarding pathogenesis, diagnosis, or treatment exists for PG. A previous pilot study using dehydrated human amniotic/chorionic membrane (dHACM), following excisional debridement, augmented PG wound healing and allowed for subsequent wound closure through split-thickness skin grafting (STSG). In this clinical trial (NCT05120726), four patients with an established PG diagnosis were enrolled to undergo treatment with dHACM and characterize the pre- and post-treatment transcriptome profiles. RNA sequencing was used to isolate the total RNA from specimens. Genes of particular interest were quantified through real-time quantitative reverse transcription polymerase chain reaction. We observed varied changes to the local expression of inflammatory response, positive regulators of cellular proliferation, and extracellular matrix disassembly cytokines. All PG wounds produced granulation tissue following treatment and were closed using split-thickness skin grafts.

A PROMPT Update on Partial REBOA: Initial Clinical Data and Overview of the DoD-Funded Partial REBOA Outcomes Multicenter ProspecTive (PROMPT) Study.

INTRODUCTION: Retrograde Endovascular Balloon Occlusion of the Aorta (REBOA) is an effective management for the transient responder, but the ischemic consequences of complete aortic occlusion currently limit its use. Multiple DoD-funded preclinical studies have clearly demonstrated that partial REBOA reduces distal ischemia to potentially extend safe occlusion times, while still providing effective temporization of noncompressible torso hemorrhage. Early versions of REBOA devices were designed to completely occlude the aorta and had little ability to provide partial occlusion. Recently, a new REBOA device (pREBOA-PRO) was designed specifically to allow for partial occlusion, with the hypothesis that this may reduce the complications of aortic occlusion and extend safe occlusion times while maintaining the benefits on cardiac and cerebrovascular circulation as well as reductions in resuscitation requirements. MATERIALS AND METHODS: To ascertain the impact of a new purpose-built partial REBOA device on the extension of safe occlusion time, the Partial REBOA Outcomes Multicenter ProspecTive (PROMPT) trial compared available data from the pREBOA-PRO with existing data from 200 clinical uses of pREBOA-PRO and available data in the AAST AORTA Registry were reviewed to design primary endpoints and clinical evidence for a prospective multi-center trial, the PROMPT Study. Together with the endpoints identified in preclinical studies of partial REBOA, primary endpoints for the PROMPT study were identified and power analyses were conducted to determine the target patient enrollment goals. RESULTS: Results from the clinical implementation of partial REBOA at a single trauma center were used to conduct the initial power analysis for the primary endpoint of Acute Kidney Injury (AKI) after prolonged occlusion. The rate of AKI after complete REBOA was 55% (12/20) compared to 33% (4/12) after partial REBOA (Madurska et al., 2021). With an alpha of 0.05 and power (ß) of 0.8, the projected sample size for comparison on a dichotomous outcome is 85 patients for the assessment of AKI. Initial power and endpoint analyses have been confirmed and extended with the ongoing analysis of partial and complete REBOA reported in the AORTA database. These analyses confirm preclinical findings which show that compared to complete REBOA, partial REBOA is associated with extended occlusion time in zone 1 (complete: 31 min vs. partial: 45 min, P = 0.003), lower rates of AKI after zone 1 occlusion (complete: 33% vs. partial: 19%, P = 0.05) and reduced resuscitation requirements (e.g., 25% reduction in pRBC administration: complete: 18 units vs. partial: 13 units, P = 0.02). CONCLUSIONS: The DoD-funded PROMPT study of partial REBOA will provide prospective observational clinical data on patients being treated with pREBOA-PRO. Outcomes will be stratified based on partial or complete occlusion to address whether partial REBOA has additional clinical benefits over complete REBOA, such as decreased distal ischemia, extension of safe occlusion time, improved hemodynamics during transition to and from occlusion, and reduced interoperative bleeding and blood product use. The results from this study are expected to confirm previous data demonstrating reduction of ischemic sequalae, improved transition to reperfusion, and reduced resuscitative requirements compared to complete REBOA.

Cytokine Profile of Adipose-Derived Stem Cells From Patients With Burn Injuries and Infection.

INTRODUCTION: Adipose-derived stem cells (ASCs) are multipotent stem cells capable of differentiating into many cell lineages. They play an important role in wound healing by secreting cytokines. Prior studies have demonstrated the presence of proinflammatory cytokines in burn wounds. However, no studies have been performed evaluating the cytokines released by burn wounds with infections. We hypothesized that there is an alteration in the paracrine factors secreted by ASCs in burn wounds with concomitant infections. METHODS: Adipose tissue was collected from patients with burn injuries at their index operation. ASCs were extracted and grown under standard tissue culture techniques. The supernatant was extracted. Cytokine analyses were performed with multiplex assays. Infection was determined using a burn sepsis protocol. The cytokine profiles of the two groups were compared using a Mann-Whitney U test. RESULTS: Sixteen patients were enrolled in the study, 50% with bacterial infection (n = 8). There was no significant difference in the baseline demographics of the two groups (P > 0.05). There were significantly lower concentrations of interleukin 13 and interferon gamma (P < 0.05) in burn patients with concomitant infections. CONCLUSIONS: ASCs are critical to burn wound healing. This study demonstrated diminished production of interleukin 13, an immunoregulatory cytokine involved in the antiinflammatory pathway by downregulating macrophage activity. This study also demonstrated significantly lower levels of interferon gamma in patient with burns and concomitant infection. This cytokine is crucial for antimicrobial defenses.

Designing Health Center Self-Measured Blood Pressure Program Models to Improve Hypertension Control.

With the aim of achieving higher, equitable hypertension control rates, 350 nationwide federally qualified health centers implemented self-measured blood pressure programs (SMBP) over a three-year grant initiative. Various SMBP program designs with systematic processes, team-based care models, and culturally sensitive approaches with improved BP control are highlighted.

Accuracy of glomerular filtration rate estimation using creatinine and cystatin C for identifying and monitoring moderate chronic kidney disease: the eGFR-C study.

Background: Estimation of glomerular filtration rate using equations based on creatinine is widely used to manage chronic kidney disease. In the UK, the Chronic Kidney Disease Epidemiology Collaboration creatinine equation is recommended. Other published equations using cystatin C, an alternative marker of kidney function, have not gained widespread clinical acceptance. Given higher cost of cystatin C, its clinical utility should be validated before widespread introduction into the NHS. Objectives: Primary objectives were to: (1) compare accuracy of glomerular filtration rate equations at baseline and longitudinally in people with stage 3 chronic kidney disease, and test whether accuracy is affected by ethnicity, diabetes, albuminuria and other characteristics; (2) establish the reference change value for significant glomerular filtration rate changes; (3) model disease progression; and (4) explore comparative cost-effectiveness of kidney disease monitoring strategies. Design: A longitudinal, prospective study was designed to: (1) assess accuracy of glomerular filtration rate equations at baseline (n = 1167) and their ability to detect change over 3 years (n = 875); (2) model disease progression predictors in 278 individuals who received additional measurements; (3) quantify glomerular filtration rate variability components (n = 20); and (4) develop a measurement model analysis to compare different monitoring strategy costs (n = 875). Setting: Primary, secondary and tertiary care. Participants: Adults (≥ 18 years) with stage 3 chronic kidney disease. Interventions: Estimated glomerular filtration rate using the Chronic Kidney Disease Epidemiology Collaboration and Modification of Diet in Renal Disease equations. Main outcome measures: Measured glomerular filtration rate was the reference against which estimating equations were compared with accuracy being expressed as P30 (percentage of values within 30% of reference) and progression (variously defined) studied as sensitivity/specificity. A regression model of disease progression was developed and differences for risk factors estimated. Biological variation components were measured and the reference change value calculated. Comparative costs of monitoring with different estimating equations modelled over 10 years were calculated. Results: Accuracy (P30) of all equations was ≥ 89.5%: the combined creatinine-cystatin equation (94.9%) was superior (p < 0.001) to other equations. Within each equation, no differences in P30 were seen across categories of age, gender, diabetes, albuminuria, body mass index, kidney function level and ethnicity. All equations showed poor (< 63%) sensitivity for detecting patients showing kidney function decline crossing clinically significant thresholds (e.g. a 25% decline in function). Consequently, the additional cost of monitoring kidney function annually using a cystatin C-based equation could not be justified (incremental cost per patient over 10 years = £43.32). Modelling data showed association between higher albuminuria and faster decline in measured and creatinine-estimated glomerular filtration rate. Reference change values for measured glomerular filtration rate (%, positive/negative) were 21.5/-17.7, with lower reference change values for estimated glomerular filtration rate. Limitations: Recruitment of people from South Asian and African-Caribbean backgrounds was below the study target. Future work: Prospective studies of the value of cystatin C as a risk marker in chronic kidney disease should be undertaken. Conclusions: Inclusion of cystatin C in glomerular filtration rate-estimating equations marginally improved accuracy but not detection of disease progression. Our data do not support cystatin C use for monitoring of glomerular filtration rate in stage 3 chronic kidney disease. Trial registration: This trial is registered as ISRCTN42955626. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 11/103/01) and is published in full in Health Technology Assessment; Vol. 28, No. 35. See the NIHR Funding and Awards website for further award information.

Chronic kidney disease, which affects approximately 14% of the adult population, often has no symptoms but, in some people, may later develop into kidney failure. Kidney disease is most often detected using a blood test called creatinine. Creatinine does not identify everyone with kidney disease, or those most likely to develop more serious kidney disease. An alternative blood test called cystatin C may be more accurate, but it is more expensive than the creatinine test. We compared the accuracy of these two tests in more than 1000 people with moderate kidney disease. Participants were tested over 3 years to see if the tests differed in their ability to detect worsening kidney function. We also wanted to identify risk factors associated with loss of kidney function, and how much the tests normally vary to better understand what results mean. We compared the accuracy and costs of monitoring people with the two markers. Cystatin C was found slightly more accurate than the creatinine test at estimating kidney function when comparing the baseline single measurements (95% accurate compared to 90%), but not at detecting worsening function over time. This means that the additional cost of monitoring people over time with cystatin C to detect kidney disease progression could not be justified. Kidney test results could vary by up to 20% between tests without necessarily implying changes in underlying kidney function ­ this is the normal level of individual variation. Cystatin C marginally improved accuracy of kidney function testing but not ability to detect worsening kidney function. Cystatin C improves identification of moderate chronic kidney disease, but our results do not support its use for routine monitoring of kidney function in such patients.

Combining the constitutive TRAIL-secreting induced neural stem cell therapy with the novel anti-cancer drug TR-107 in glioblastoma.

Tumor-homing neural stem cell (NSC) therapy is emerging as a promising treatment for aggressive cancers of the brain. Despite their success, developing tumor-homing NSC therapy therapies that maintain durable tumor suppression remains a challenge. Herein, we report a synergistic combination regimen where the novel small molecule TR-107 augments NSC-tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) therapy (hiNeuroS-TRAIL) in models of the incurable brain cancer glioblastoma (GBM) in vitro. We report that the combination of hiNeuroS-TRAIL and TR-107 synergistically upregulated caspase markers and restored sensitivity to the intrinsic apoptotic pathway by significantly downregulating inhibitory pathways associated with chemoresistance and radioresistance in the TRAIL-resistant LN229 cell line. This combination also showed robust tumor suppression and enhanced survival of mice bearing human xenografts of both solid and invasive GBMs. These findings elucidate a novel combination regimen and suggest that the combination of these clinically relevant agents may represent a new therapeutic option with increased efficacy for patients with GBM.

Does the use of double hormone replacement therapy for trauma patient organ donors improve organ recovery for transplant.

BACKGROUND: With an ongoing demand for transplantable organs, optimization of donor management protocols, specifically in trauma populations, is important for obtaining a high yield of viable organs per patient. Endocrine management of brain-dead potential organ donors (BPODs) is controversial, leading to heterogeneous clinical management approaches. Previous studies have shown that when levothyroxine was combined with other treatments, including steroids, vasopressin, and insulin, BPODs had better organ recovery and survival outcomes were increased for transplant recipients. AIM: To determine if levothyroxine use in combination with steroids in BPODs increased the number of organs donated in trauma patients. METHODS: A retrospective review of adult BPODs from a single level 1 trauma center over ten years was performed. Exclusion criteria included patients who were not solid organ donors, patients who were not declared brain dead (donation after circulatory death), and patients who did not receive steroids in their hospital course. Levothyroxine and steroid administration, the number of organs donated, the types of organs donated, and demographic information were recorded. Univariate analyses were performed with P < 0.05 considered to be statistically significant. RESULTS: A total of 88 patients met inclusion criteria, 69 (78%) of whom received levothyroxine and steroids (ST/LT group) vs 19 (22%) receiving steroids without levothyroxine (ST group). No differences were observed between the groups for gender, race, pertinent injury factors, age, or other hormone therapies used (P > 0.05). In the ST/LT group, 68.1% (n = 47) donated a high yield (3-5) of organ types per donor compared to 42.1% (n = 8) in the ST group (P = 0.038). There was no difference in the total number of organ types donated between the groups (P = 0.068). CONCLUSION: This study suggests that combining levothyroxine and steroid administration increases high-yield organ donation per donor in BPODs in the trauma patient population. Limitations to this study include the retrospective design and the relatively small number of organ donors who met inclusion criteria. This study is unique in that it mitigates steroid administration as a confounding variable and focuses specifically on the adjunctive use of levothyroxine.

Time to Positive Blood Cultures Among Critically Ill Children Admitted to the PICU.

OBJECTIVES: Our study aimed to assess the time to positivity (TTP) of clinically significant blood cultures in critically ill children admitted to the PICU. DESIGN: Retrospective review of positive blood cultures in patients admitted or transferred to the PICU. SETTING: Large tertiary-care medical center with over 90 PICU beds. PATIENTS: Patients 0-20 years old with bacteremia admitted or transferred to the PICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was the TTP, defined as time from blood culture draw to initial Gram stain result. Secondary endpoints included percentage of cultures reported by elapsed time, as well as the impact of pathogen and host immune status on TTP. Host immune status was classified as previously healthy, standard risk, or immunocompromised. Linear regression for TTP was performed to account for age, blood volume, and Gram stain. Among 164 episodes of clinically significant bacteremia, the median TTP was 13.3 hours (interquartile range, 10.7-16.8 hr). Enterobacterales, Staphylococcus aureus, Streptococcus agalactiae, and Streptococcus pneumoniae were most commonly identified. By 12, 24, 36, and 48 hours, 37%, 89%, 95%, and 97% of positive cultures had resulted positive, respectively. Median TTP stratified by host immune status was 13.2 hours for previously healthy patients, 14.0 hours for those considered standard risk, and 10.6 hours for immunocompromised patients (p = 0.001). Median TTP was found to be independent of blood volume. No difference was seen in TTP for Gram-negative vs. Gram-positive organisms (12.2 vs. 13.9 hr; p = 0.2). CONCLUSIONS: Among critically ill children, 95% of clinically significant blood cultures had an initial positive result within 36 hours, regardless of host immune status. Need for antimicrobial therapy should be frequently reassessed and implementation of a shorter duration of empiric antibiotics should be considered in patients with low suspicion for infection.

Splenic artery embolization in the treatment of blunt splenic injury: single level 1 trauma center experience.

PURPOSE: To describe the experience of a single level 1 trauma center in the management of blunt splenic injuries (BSI). METHODS: This is a retrospective study with Institutional Review Board approval. The medical records of 450 patients with BSI treated between January 2016 and December 2022 were reviewed. Seventy-two patients were treated with splenic artery embolization (SAE), met the study criteria, and were eligible for data analysis. Spleen injuries were graded in accordance with the American Association for the Surgery of Trauma Organ Injury Scale. Univariate data analysis was performed, with P < 0.05 considered statistically significant. RESULTS: The splenic salvage rate was 90.3% (n = 65/72). Baseline demographics were similar between the groups (P > 0.05). Distal embolization with Gelfoam® had similar rates of splenic salvage to proximal embolization with coils (90% vs. 94.1%, P > 0.05). There was no significant difference in the rate of splenic infarction between distal embolization with Gelfoam® (20%, 4/20) and proximal embolization with coils (17.6%, 3/17) (P > 0.05). There was no significant difference in procedure length (68 vs. 75.8 min) or splenic salvage rate (88.5% vs. 92.1%) between proximal and distal embolization (P > 0.05). There was no significant difference in procedure length (69.1 vs. 73.6 min) or splenic salvage rate (93.1% vs. 86.4%) between Gelfoam® and coil embolization (P > 0.05). Combined proximal and distal embolization was associated with a higher rate of splenic abscess formation (25%, 2/8) when compared with proximal (0%, 0/26) or distal (0%, 0/38) embolization alone (P = 0.0003). The rate of asymptomatic and symptomatic splenic infarction was significantly higher in patients embolized at combined proximal and distal locations (P = 0.04, P = 0.01). CONCLUSION: The endovascular management of BSI is safe and effective. The overall splenic salvage rate was 90.3%. Distal embolization with Gelfoam® was not associated with higher rates of splenic infarction when compared with proximal embolization with coils. Combined proximal and distal embolization was associated with a higher incidence of splenic infarction and splenic abscess formation. CLINICAL SIGNIFICANCE: Distal splenic embolization with Gelfoam® is safe and may be beneficial in the setting of blunt splenic trauma.

Photobiomodulation Treatment with a Home-Use Device for COVID-19: A Randomized Controlled Trial for Efficacy and Safety.

Background: Photobiomodulation therapy (PBMT) using devices to deliver red and/or near-infrared light to tissues has shown promising effects in clinical settings for respiratory diseases, including potential benefits in managing symptoms associated with COVID-19. Objective: To determine if at-home self-administered PBMT for patients with COVID-19 is safe and effective. Methods: This was a randomized controlled trial (RCT) carried out at home during the COVID-19 pandemic (September 2020 to August 2021). The treatment group self-administered the Vielight RX Plus PBMT device (635 nm intranasal and 810 nm chest LEDs) and were monitored remotely. Eligible patients scored 4-7 (out of 7) for severity on the Wisconsin Upper Respiratory Symptom Survey (WURSS-44). Patients were randomized equally to Control group receiving standard-of-care (SOC) only or Treatment group receiving SOC plus PBMT. The device was used for 20 min 2X/day for 5 days and, subsequently, once daily for 30 days. The primary end-point was time-to-recovery (days) based on WURSS-44 question 1, "How sick do you feel today?". Subgroup analysis was performed, and Kaplan-Meier and Cox Proportional Hazards analysis were employed. Results: One hundred and ninety-nine eligible patients (18-65 years old) were divided into two subgroups as follows: 136 patients with 0-7 days of symptoms at baseline and 63 patients with 8-12 days of symptoms. Those with 0-7 days of symptoms at baseline recovered significantly faster with PBMT. The median for Treatment group was 18 days [95% confidence interval (CI), 13-20] versus the Control group 21 days (95% CI, 15-28), p = 0.050. The treatment:control hazard ratio was 1.495 (95% CI, 0.996-2.243), p = 0.054. Patients with symptom duration ≥7 days did not show any significant improvement. No deaths or severe adverse events (SAEs) occurred in the Treatment group, whereas there was 1 death and 3 SAEs requiring hospitalization in the Control group. Conclusions: Patients with ≤7 days of COVID-19 symptoms recovered significantly faster with PBMT compared to SOC. Beyond 7 days, PBMT showed no superiority over SOC. Trial Registration: ClinicalTrials.gov NCT04418505.

Beyond Infection: Mortality and End-of-Life Care Associated with Infectious Disease Consultation in an Academic Health System.

BACKGROUND: Infectious diseases (ID) physicians are increasingly faced with the challenge of caring for patients with terminal illnesses or incurable infections. METHODS: This was a retrospective cohort of all patients with an ID consult within an academic health system 1/1/2014 - 12/31/2023, including community, general, and transplant ID consult services. RESULTS: There were 60,820 inpatient ID consults (17,235 community, 29,999 general, and 13,586 transplant) involving 37,848 unique patients. The number of consults increased by 94% and the rate rose from 5.0 to 9.9 consults per 100 inpatients (p<0.001). In total, 7.5% of patients receiving an ID consult died during admission, and 1,006 (2.6%) of patients were discharged to hospice. In-hospital mortality was 5.2% for community ID, 7.8% for general ID, and 10.7% for transplant ID patients (p<0.001). Six-month mortality was 9% for all non-obstetric admissions, , vs. 19% for community ID, 20.9% for general ID, and 22.3% for transplant ID.In total 2,866 (7.6%) of all patients receiving ID consultation also received palliative care consultation during the same hospitalization. The index ID consult preceded any palliative consult in the majority (69.5%) of cases. 16.3% of patients had a do-not-resuscitate order during the index hospitalization. 12.2% of all patients with a do-not-resuscitate order had this placed on the same day as the ID consult. CONCLUSIONS: Patients receiving ID consultation were increasingly complex and more likely to die soon after consultation. These results provide a framework for ID clinicians to consider their role in end-of-life care.

Nutritional Screening, Initial Management and Referral for Older People with Sarcopenia or Frailty - Results from a UK-Wide Survey.

Objectives: We surveyed healthcare staff working with older people to understand current practice in nutrition screening, initial management and referral for older people with sarcopenia and frailty. Methods: We conducted a UK-wide web-based survey of staff working with older people in both hospital and community settings. Surveys were distributed through professional organisation e-mail lists and social media channels. Descriptive data were generated from categorical responses and inductive thematic analysis was applied to free-text responses. Results: Data were analysed from 169 respondents (110 hospital, 59 community), representing 99 healthcare organisations. 91 (83%) hospital respondents and 24 (41%) community respondents reported that nutrition screening was performed on all patients with sarcopenia or frailty. The Malnutrition Universal Screening Tool was most commonly used to trigger referral to dietetics teams, but there was considerable variation in management before referral, referral thresholds and referral pathways. Themes derived from free-text responses included the need for training, issues of responsibility and ownership, inadequate resources (time, staff and equipment) and ineffective or inefficient processes for referral and management. Conclusions: Current UK nutritional care for older people with sarcopenia and frailty is heterogeneous. There are opportunities for better tools, processes, training and resources to improve current practice and pathways.

Every minute matters: Improving outcomes for penetrating trauma through prehospital advanced resuscitative care.

INTRODUCTION: Prehospital resuscitation with blood products is gaining popularity for patients with traumatic hemorrhage. The MEDEVAC trial demonstrated a survival benefit exclusively among patients who received blood or plasma within 15 minutes of air medical evacuation. In fast-paced urban EMS systems with a high incidence of penetrating trauma, mortality data based on the timing to first blood administration is scarce. We hypothesize a survival benefit in patients with severe hemorrhage when blood is administered within the first 15 minutes of EMS patient contact. METHODS: This was a retrospective analysis of a prospective database of prehospital blood (PHB) administration between 2021 and 2023 in an urban EMS system facing increasing rates of gun violence. PHB patients were compared to trauma registry controls from an era before prehospital blood utilization (2016-2019). Included were patients with penetrating injury and SBP ≤ 90 mmHg at initial EMS evaluation that received at least one unit of blood product after injury. Excluded were isolated head trauma or prehospital cardiac arrest. Time to initiation of blood administration before and after PHB implementation and in-hospital mortality were the primary variables of interest. RESULTS: A total of 143 patients (PHB = 61, controls = 82) were included for analysis. Median age was 34 years with no difference in demographics. Median scene and transport intervals were longer in the PHB cohort, with a 5-minute increase in total prehospital time. Time to administration of first unit of blood was significantly lower in the PHB vs. control group (8 min vs 27 min; p < 0.01). In-hospital mortality was lower in the PHB vs. control group (7% vs 29%; p < 0.01). When controlling for patient age, NISS, tachycardia on EMS evaluation, and total prehospital time interval, multivariate regression revealed an independent increase in mortality by 11% with each minute delay to blood administration following injury (OR 1.11, 95%CI 1.04-1.19). CONCLUSION: Compared to patients with penetrating trauma and hypotension who first received blood after hospital arrival, resuscitation with blood products was started 19 minutes earlier after initiation of a PHB program despite a 5-minute increase in prehospital time. A survival for early PHB use was demonstrated, with an 11% mortality increase for each minute delay to blood administration. Interventions such as PHB may improve patient outcomes by helping capture opportunities to improve trauma resuscitation closer to the point of injury. LEVEL OF EVIDENCE: Prospective, Level IV.

Clinical outcomes in patients with piperacillin/tazobactam-non-susceptible but ceftriaxone-susceptible E. coli or K. pneumoniae bloodstream infection.

BACKGROUND: A small proportion of Escherichia coli and Klebsiella pneumoniae demonstrate in vitro non-susceptibility to piperacillin/tazobactam but retain susceptibility to ceftriaxone. Uncertainty remains regarding how best to treat these isolates. OBJECTIVES: We sought to compare clinical outcomes between patients with piperacillin/tazobactam-non-susceptible but ceftriaxone-susceptible E. coli or K. pneumoniae bloodstream infection receiving definitive therapy with ceftriaxone versus an alternative effective antibiotic. METHODS: We retrospectively identified patients with a positive blood culture for piperacillin/tazobactam-non-susceptible but ceftriaxone-susceptible E. coli or K. pneumoniae between 1 January 2013 and 31 December 2022. Patients were divided into one of two definitive treatment groups: ceftriaxone or alternative effective antibiotic. Our primary outcome was a composite of 90 day all-cause mortality, hospital readmission, or recurrence of infection. We used Cox proportional hazards models to compare time with the composite outcome between groups. RESULTS: Sixty-two patients were included in our analysis. Overall, median age was 63 years (IQR 49.5-71.0), the most common source of infection was intra-abdominal (25/62; 40.3%) and the median total duration of therapy was 12.0 days (IQR 9.0-16.8). A total of 9/22 (40.9%) patients in the ceftriaxone treatment group and 18/40 (45.0%) patients in the alternative effective antibiotic group met the composite endpoint. In an adjusted time-to-event analysis, there was no difference in the composite endpoint between groups (HR 0.67, 95% CI 0.30-1.50). The adjusted Bayesian posterior probability that the HR was less than or equal to 1 (i.e. ceftriaxone is as good or better than alternative therapy) was 85%. CONCLUSIONS: These findings suggest that ceftriaxone can be used to effectively treat bloodstream infections with E. coli or K. pneumoniae that are non-susceptible to piperacillin/tazobactam but susceptible to ceftriaxone.

The impact of post-operative enteral nutrition on duodenal injury outcomes: A post hoc analysis of an EAST multicenter trial.

BACKGROUND: Leak following surgical repair of traumatic duodenal injuries results in prolonged hospitalization and oftentimes nil per os(NPO) treatment. Parenteral nutrition(PN) has known morbidity; however, duodenal leak(DL) patients often have complex injuries and hospital courses resulting in barriers to enteral nutrition(EN). We hypothesized EN alone would be associated with 1)shorter duration until leak closure and 2)less infectious complications and shorter hospital length of stay(HLOS) compared to PN. METHODS: This was a post-hoc analysis of a retrospective, multicenter study from 35 Level-1 trauma centers, including patients >14 years-old who underwent surgery for duodenal injuries(1/2010-12/2020) and endured post-operative DL. The study compared nutrition strategies: EN vs PN vs EN + PN using Chi-Square and Kruskal-Wallis tests; if significance was found pairwise comparison or Dunn's test were performed. RESULTS: There were 113 patients with DL: 43 EN, 22 PN, and 48 EN + PN. Patients were young(median age 28 years-old) males(83.2%) with penetrating injuries(81.4%). There was no difference in injury severity or critical illness among the groups, however there were more pancreatic injuries among PN groups. EN patients had less days NPO compared to both PN groups(12 days[IQR23] vs 40[54] vs 33[32],p = <0.001). Time until leak closure was less in EN patients when comparing the three groups(7 days[IQR14.5] vs 15[20.5] vs 25.5[55.8],p = 0.008). EN patients had less intra-abdominal abscesses, bacteremia, and days with drains than the PN groups(all p < 0.05). HLOS was shorter among EN patients vs both PN groups(27 days[24] vs 44[62] vs 45[31],p = 0.001). When controlling for predictors of leak, regression analysis demonstrated EN was associated with shorter HLOS(ß -24.9, 95%CI -39.0 to -10.7,p < 0.001). CONCLUSION: EN was associated with a shorter duration until leak closure, less infectious complications, and shorter length of stay. Contrary to some conventional thought, PN was not associated with decreased time until leak closure. We therefore suggest EN should be the preferred choice of nutrition in patients with duodenal leaks whenever feasible. LEVEL OF EVIDENCE: IV.

Light management by algal aggregates in living photosynthetic hydrogels.

Rapid progress in algal biotechnology has triggered a growing interest in hydrogel-encapsulated microalgal cultivation, especially for the engineering of functional photosynthetic materials and biomass production. An overlooked characteristic of gel-encapsulated cultures is the emergence of cell aggregates, which are the result of the mechanical confinement of the cells. Such aggregates have a dramatic effect on the light management of gel-encapsulated photobioreactors and hence strongly affect the photosynthetic outcome. To evaluate such an effect, we experimentally studied the optical response of hydrogels containing algal aggregates and developed optical simulations to study the resultant light intensity profiles. The simulations are validated experimentally via transmittance measurements using an integrating sphere and aggregate volume analysis with confocal microscopy. Specifically, the heterogeneous distribution of cell aggregates in a hydrogel matrix can increase light penetration while alleviating photoinhibition more effectively than in a flat biofilm. Finally, we demonstrate that light harvesting efficiency can be further enhanced with the introduction of scattering particles within the hydrogel matrix, leading to a fourfold increase in biomass growth. Our study, therefore, highlights a strategy for the design of spatially efficient photosynthetic living materials that have important implications for the engineering of future algal cultivation systems.

Applying the Milan models to setting analytical performance specifications - considering all the information.

Analytical performance specifications (APS) are used for decisions about the required analytical quality of pathology tests to meet clinical needs. The Milan models, based on clinical outcome, biological variation, or state of the art, were developed to provide a framework for setting APS. An approach has been proposed to assign each measurand to one of the models based on a defined clinical use, physiological control, or an absence of quality information about these factors. In this paper we propose that in addition to such assignment, available information from all models should be considered using a risk-based approach that considers the purpose and role of the actual test in a clinical pathway and its impact on medical decisions and clinical outcomes in addition to biological variation and the state-of-the-art. Consideration of APS already in use and the use of results in calculations may also need to be considered to determine the most appropriate APS for use in a specific setting.