Predicting 5-year dementia conversion in veterans with mild cognitive impairment.

INTRODUCTION: Identifying mild cognitive impairment (MCI) patients at risk for dementia could facilitate early interventions. Using electronic health records (EHRs), we developed a model to predict MCI to all-cause dementia (ACD) conversion at 5 years. METHODS: Cox proportional hazards model was used to identify predictors of ACD conversion from EHR data in veterans with MCI. Model performance (area under the receiver operating characteristic curve [AUC] and Brier score) was evaluated on a held-out data subset. RESULTS: Of 59,782 MCI patients, 15,420 (25.8%) converted to ACD. The model had good discriminative performance (AUC 0.73 [95% confidence interval (CI) 0.72-0.74]), and calibration (Brier score 0.18 [95% CI 0.17-0.18]). Age, stroke, cerebrovascular disease, myocardial infarction, hypertension, and diabetes were risk factors, while body mass index, alcohol abuse, and sleep apnea were protective factors. DISCUSSION: EHR-based prediction model had good performance in identifying 5-year MCI to ACD conversion and has potential to assist triaging of at-risk patients. Highlights: Of 59,782 veterans with mild cognitive impairment (MCI), 15,420 (25.8%) converted to all-cause dementia within 5 years.Electronic health record prediction models demonstrated good performance (area under the receiver operating characteristic curve 0.73; Brier 0.18).Age and vascular-related morbidities were predictors of dementia conversion.Synthetic data was comparable to real data in modeling MCI to dementia conversion. Key Points: An electronic health record-based model using demographic and co-morbidity data had good performance in identifying veterans who convert from mild cognitive impairment (MCI) to all-cause dementia (ACD) within 5 years.Increased age, stroke, cerebrovascular disease, myocardial infarction, hypertension, and diabetes were risk factors for 5-year conversion from MCI to ACD.High body mass index, alcohol abuse, and sleep apnea were protective factors for 5-year conversion from MCI to ACD.Models using synthetic data, analogs of real patient data that retain the distribution, density, and covariance between variables of real patient data but are not attributable to any specific patient, performed just as well as models using real patient data. This could have significant implications in facilitating widely distributed computing of health-care data with minimized patient privacy concern that could accelerate scientific discoveries.

Changes in neurologic status after traumatic brain injury in the Resuscitation Outcomes Consortium Hypertonic Saline trial.

Objectives: Traumatic brain injury (TBI) is an important public health problem resulting in significant death and disability. Emergency medical services (EMS) personnel often provide initial treatment for TBI, but only limited data describe the long-term course and outcomes of this care. We sought to characterize changes in neurologic status among adults with TBI patients enrolled in the Resuscitation Outcomes Consortium Hypertonic Saline (ROC-HS) trial. Methods: We used data from the TBI cohort of the ROC-HS trial. The trial included adults with TBI, with Glasgow Coma Scale (GCS) ≤8, and excluded those with shock (systolic blood pressure [SBP] ≤70 or SBP 71-90 with a heart rate [HR] ≥108). The primary outcome was Glasgow Outcome Scale-Extended (GOS-E; 1 = dead, 8 = no disability) determined at (a) hospital discharge and (b) 6-month follow-up. We assessed changes in GOS-E between hospital discharge and 6-month follow-up using descriptive statistics and Sankey graphs. Results: Among 1279 TBI included in the analysis, GOS-E categories at hospital discharge were as follows: favorable (GOS-E 5-8) 220 (17.2%), unfavorable (GOS-E 2-4) 664 (51.9%), dead (GOS-E 1) 321 (25.1%), and missing 74 (5.8%). GOS-E categories at 6-month follow-up were as follows: favorable 459 (35.9%), unfavorable 279 (21.8%), dead 346 (27.1%), and missing 195 (15.2%). Among initial TBI survivors with complete GOS-E, >96% followed one of three neurologic recovery patterns: (1) favorable to favorable (20.0%), (2) unfavorable to favorable (40.3%), and (3) unfavorable to unfavorable (36.0%). Few patients deteriorated from favorable to unfavorable neurologic status, and there were few additional deaths. Conclusions: Among TBI receiving initial prehospital care in the ROC-HS trial, changes in 6-month neurologic status followed distinct patterns. Among TBI with unfavorable neurologic status at hospital discharge, almost half improved to favorable neurologic status at 6 months. Among those with favorable neurologic status at discharge, very few worsened or died at 6 months. These findings have important implications for TBI clinical care, research, and trial design.

Vitamin D and prebiotics for intestinal health in cystic fibrosis: Rationale and design for a randomized, placebo-controlled, double-blind, 2 x 2 trial of administration of prebiotics and cholecalciferol (vitamin D3) (Pre-D trial) in adults with cystic fibrosis.

Individuals with cystic fibrosis (CF) have dysfunctional intestinal microbiota and increased gastrointestinal (GI) inflammation also known as GI dysbiosis. It is hypothesized that administration of high-dose cholecalciferol (vitamin D3) together with a prebiotic (inulin) will be effective, and possibly additive or synergistic, in reducing CF-related GI and airway dysbiosis. Thus, a 2 x 2 factorial design, placebo-controlled, double-blinded, pilot and feasibility, clinical trial was proposed to test this hypothesis. Forty adult participants with CF were block-randomized into one of four groups: 1) high-dose oral vitamin D3 (50,000 IU weekly) plus oral prebiotic placebo daily; 2) oral prebiotic (12 g inulin daily) plus oral placebo vitamin D3 weekly; 3) combined oral vitamin D3 weekly and oral prebiotic inulin daily; and 4) oral vitamin D3 placebo weekly and oral prebiotic placebo. The primary endpoints included 12-week changes in the microbial bacterial communities, gut and airway microbiota richness and diversity before and after the intervention. This pilot study examined whether vitamin D3 with or without prebiotics supplementation was feasible, changed airway and gut microbiota, and reduced dysbiosis, which in turn, may improve health outcomes and quality of life of patients with CF.

Organization of microtubule plus-end dynamics by phase separation in mitosis.

In eukaryotes, microtubule polymers are essential for cellular plasticity and fate decisions. End-binding (EB) proteins serve as scaffolds for orchestrating microtubule polymer dynamics and are essential for cellular dynamics and chromosome segregation in mitosis. Here, we show that EB1 forms molecular condensates with TIP150 and MCAK through liquid-liquid phase separation to compartmentalize the kinetochore-microtubule plus-end machinery, ensuring accurate kinetochore-microtubule interactions during chromosome segregation in mitosis. Perturbation of EB1-TIP150 polymer formation by a competing peptide prevents phase separation of the EB1-mediated complex and chromosome alignment at the metaphase equator in both cultured cells and Drosophila embryos. Lys220 of EB1 is dynamically acetylated by p300/CBP-associated factor in early mitosis, and persistent acetylation at Lys220 attenuates the phase separation of the EB1-mediated complex, dissolves droplets in vitro, and harnesses accurate chromosome segregation. Our data suggest a novel framework for understanding the organization and regulation of eukaryotic spindle for accurate chromosome segregation in mitosis.

Inhibition of UV-Induced Stress Signaling and Inflammatory Responses in SKH-1 Mouse Skin by Topical Small-Molecule PD-L1 Blockade.

The immune checkpoint ligand PD-L1 has emerged as a molecular target for skin cancer therapy and might also hold promise for preventive intervention targeting solar UV light-induced skin damage. In this study, we have explored the role of PD-L1 in acute keratinocytic photodamage testing the effects of small-molecule pharmacological inhibition. Epidermal PD-L1 upregulation in response to chronic photodamage was established using immunohistochemical and proteomic analyses of a human skin cohort, consistent with earlier observations that PD-L1 is upregulated in cutaneous squamous cell carcinoma. Topical application of the small-molecule PD-L1 inhibitor BMS-202 significantly attenuated UV-induced activator protein-1 transcriptional activity in SKH-1 bioluminescent reporter mouse skin, also confirmed in human HaCaT reporter keratinocytes. RT-qPCR analysis revealed that BMS-202 antagonized UV induction of inflammatory gene expression. Likewise, UV-induced cleavage of procaspase-3, a hallmark of acute skin photodamage, was attenuated by topical BMS-202. NanoString nCounter transcriptomic analysis confirmed downregulation of cutaneous innate immunity- and inflammation-related responses, together with upregulation of immune response pathway gene expression. Further mechanistic analysis confirmed that BMS-202 antagonizes UV-induced PD-L1 expression both at the mRNA and protein levels in SKH-1 epidermis. These data suggest that topical pharmacological PD-L1 antagonism using BMS-202 shows promise for skin protection against photodamage.

Vitamin D and Prebiotics for Intestinal Health in Cystic Fibrosis: Rationale and design for a randomized, placebo-controlled, double-blind, 2 × 2 trial of administration of prebiotics and cholecalciferol (vitamin D3) (Pre-D Trial) in adults with cystic fibrosis.

Individuals with cystic fibrosis (CF) have dysfunctional intestinal microbiota and increased gastrointestinal (GI) inflammation also known as GI dysbiosis. It is hypothesized that administration of high-dose cholecalciferol (vitamin D3) together with a prebiotic (inulin) will be effective, and possibly additive or synergistic, in reducing CF-related GI dysbiosis and improving intestinal functions. Thus, a 2 × 2 factorial design, placebo-controlled, double-blind, clinical trial was proposed to test this hypothesis. Forty adult participants with CF will be block-randomized into one of four groups: 1) high-dose oral vitamin D3 (50,000 IU weekly) plus oral prebiotic placebo daily; 2) oral prebiotic (12 g inulin daily) plus oral placebo vitamin D3 weekly; 3) combined oral vitamin D3 weekly and oral prebiotic inulin daily; and 4) oral vitamin D3 placebo weekly and oral prebiotic placebo. The primary endpoints will include 12-week changes in the reduced relative abundance of gammaproteobacteria, and gut microbiota richness and diversity before and after the intervention. This clinical study will examine whether vitamin D3 with or without prebiotics will improve intestinal health and reduce GI dysbiosis, which in turn, should improve health outcomes and quality of life of patients with CF.

EMS Treatment Guidelines in Major Traumatic Brain Injury With Positive Pressure Ventilation.

Importance: The Excellence in Prehospital Injury Care (EPIC) study demonstrated improved survival in patients with severe traumatic brain injury (TBI) following implementation of the prehospital treatment guidelines. The impact of implementing these guidelines in the subgroup of patients who received positive pressure ventilation (PPV) is unknown. Objective: To evaluate the association of implementation of prehospital TBI evidence-based guidelines with survival among patients with prehospital PPV. Design, Setting, and Participants: The EPIC study was a multisystem, intention-to-treat study using a before/after controlled design. Evidence-based guidelines were implemented by emergency medical service agencies across Arizona. This subanalysis was planned a priori and included participants who received prehospital PPV. Outcomes were compared between the preimplementation and postimplementation cohorts using logistic regression, stratified by predetermined TBI severity categories (moderate, severe, or critical). Data were collected from January 2007 to June 2017, and data were analyzed from January to February 2023. Exposure: Implementation of the evidence-based guidelines for the prehospital care of patient with TBI. Main Outcomes and Measures: The primary outcome was survival to hospital discharge, and the secondary outcome was survival to admission. Results: Among the 21 852 participants in the main study, 5022 received prehospital PPV (preimplementation, 3531 participants; postimplementation, 1491 participants). Of 5022 included participants, 3720 (74.1%) were male, and the median (IQR) age was 36 (22-54) years. Across all severities combined, survival to admission improved (adjusted odds ratio [aOR], 1.59; 95% CI, 1.28-1.97), while survival to discharge did not (aOR, 0.94; 95% CI, 0.78-1.13). Within the cohort with severe TBI but not in the moderate or critical subgroups, survival to hospital admission increased (aOR, 6.44; 95% CI, 2.39-22.00), as did survival to discharge (aOR, 3.52; 95% CI, 1.96-6.34). Conclusions and Relevance: Among patients with severe TBI who received active airway interventions in the field, guideline implementation was independently associated with improved survival to hospital admission and discharge. This was true whether they received basic airway interventions or advanced airways. These findings support the current guideline recommendations for aggressive prevention/correction of hypoxia and hyperventilation in patients with severe TBI, regardless of which airway type is used.

Botryorhodine J, a new anti-MRSA depsidone isolated from endophytic fungus Alternaria alternata Pas11.

A new depsidone derivative botryorhodine J (1), along with six known compounds (2-7) were obtained from solid rice cultures of Alternaria alternata Pas11 that was isolated from leaves of Phragmites australis. The structure of the new compound was elucidated on the basis of combination of NMR spectroscopic data and high resolution mass spectrometry (HRMS). All the isolated compounds were evaluated for their antibacterial activities against a panel of Gram-positive bacterial strains (methicillin-resistant Staphylococcus aureus [MRSA], Bacillus subtilis and S. aureus). Compounds 1 and 6 displayed antibacterial activity against the three bacterial strains with the minimum inhibitory concentration values (MICs) of 14 - 32 µg/mL, while compound 5 showed good antibacterial activity against above bacterial strains with MIC values of 5 - 8 µg/mL.

Antimicrobial Resistance Risk Assessment of Vibrio parahaemolyticus Isolated from Farmed Green Mussels in Singapore.

Vibrio parahaemolyticus, commonly found in seafood products, is responsible for gastroenteritis resulting from the consumption of undercooked seafood. Hence, there is a need to characterize and quantify the risk involved from this pathogen. However, there has been no study reporting the quantification of hemolytic antimicrobial-resistant (AMR) Vibrio parahaemolyticus in locally farmed shellfish in Singapore. In this study, ampicillin, penicillin G, tetracycline resistant, and non-AMR hemolytic V. parahaemolyticus were surveyed and quantified in green mussel samples from different premises in the food chain (farm and retail). The occurrence data showed that 31/45 (68.9%) of farmed green mussel samples, 6/6 (100%) farm water samples, and 41/45 (91.1%) retail shellfish samples detected the presence of hemolytic V. parahaemolyticus. V. parahaemolyticus counts ranged from 1.6-5.9 Log CFU/g in the retail shellfish samples and 1.0-2.9 Log CFU/g in the farm water samples. AMR risk assessments (ARRA), specifically for ampicillin, penicillin G, tetracycline, and hemolytic (non-AMR) scenarios were conducted for the full farm-to-home and partial retail-to-home chains. The hemolytic ARRA scenario estimated an average probability of illness of 5.7 × 10-3 and 1.2 × 10-2 per serving for the full and partial chains, respectively, translating to 165 and 355 annual cases per total population or 2.9 and 6.2 cases per 100,000 population, respectively. The average probability of illness per year ratios for the three ARRAs to the hemolytic ARRA were 0.82, 0.81, and 0.47 (ampicillin, penicillin G, and tetracycline, respectively) for the full chain and 0.54, 0.39, and 0.09 (ampicillin, penicillin G, and tetracycline, respectively) for the partial chain. The sensitivity analysis showed that the overall cooking effect, initial concentrations of pathogenic V. parahaemolyticus, and harvest duration and harvest temperature were key variables influencing the risk estimates in all of the modelled ARRAs. The study findings can be used by relevant stakeholders to make informed decisions for risk management that improve food safety.

Thiol-Aldehyde Polycondensation for Bio-based Adaptable and Degradable Phenolic Polymers.

Designing sustainable materials with tunable mechanical properties, intrinsic degradability, and recyclability from renewable biomass through a mild process has become vital in polymer science. Traditional phenolic resins are generally considered to be not degradable or recyclable. Here we report the design and synthesis of linear and network structured phenolic polymers using facile polycondensation between natural aldehyde-bearing phenolic compounds and polymercaptans. Linear phenolic products are amorphous with Tg between -9 °C and 12 °C. Cross-linked networks from vanillin and its di-aldehyde derivative exhibited excellent mechanical strength between 6-64 MPa. The connecting dithioacetals are associatively adaptable strong bonds and susceptible to degradation in oxidative conditions to regenerate vanillin. These results highlight the potential of biobased sustainable phenolic polymers with recyclability and selective degradation, as a complement to the traditional phenol-formaldehyde resins.

Antidepressants amitriptyline, fluoxetine, and traditional Chinese medicine Xiaoyaosan caused alterations in gut DNA virome composition and function in rats exposed chronic unpredictable mild stress.

Background: In clinical practice, antidepressant drugs are widely used to treat depression. Previous studies have attention to the impact of antidepressants on the bacterial microbiome, while the role of these drugs in the gut virome is still unclear. Methods: In this study, we estimated the effects of antidepressant amitriptyline (Ami), fluoxetine (Flu), and traditional Chinese medicine Xiaoyaosan (XYS) administration on gut viral composition and function in a chronic unpredictable mild stress (CUMS)-induced depression rat model based on shotgun metagenomic sequencing. Results: The results showed that treatment with Ami, Flu, and XYS significantly changed the gut viral composition compared with the CUMS-induced rats. At the family level, the abundance of f_unclassified_Caudovirales in CUMS rats was remarkably lower than in the HC rats, nevertheless, XYS significantly recovered the abundance of Caudovirales. Meanwhile, the abundance of Podoviridae was expanded in CUMS rats compared with the HC rats, and the profile was then significantly reduced after XYS treatment. Furthermore, both antidepressants and XYS increased the abundance of Siphoviridae compared with the CUMS rats, but only Ami treatments had significant differences. Subsequent function annotation further implied that Ami, Flu, and XYS showed to involve an alteration of the diverse viral functions, such as carbohydrate metabolism, xenobiotics biodegradation and metabolism, community-prokaryotes, translation, and neurodegenerative disease. Additionally, the co-occurrence network displayed that there are complex interactions between viral operational taxonomic units (vOTUs) represented by temperate phages and the majority of bacterial genera in the intestine ecosystem. Conclusion: Our study proved for the first time that depression is characterized by massive alterations and functional distortion of the gut viruses, and after oral administration of Ami, Flu, and XYS could affect disordered gut virome, which could be a novel target in depression.

A multiple imputation-based sensitivity analysis approach for regression analysis with a missing not at random covariate.

Missing covariate problems are common in biomedical and electrical medical record data studies while evaluating the relationship between a biomarker and certain clinical outcome, when biomarker data are not collected for all subjects. However, missingness mechanism is unverifiable based on observed data. If there is a suspicion of missing not at random (MNAR), researchers often perform sensitivity analysis to evaluate the impact of various missingness mechanisms. Under the selection modeling framework, we propose a sensitivity analysis approach with a standardized sensitivity parameter using a nonparametric multiple imputation strategy. The proposed approach requires fitting two working models to derive two predictive scores: one for predicting missing covariate values and the other for predicting missingness probabilities. For each missing covariate observation, the two predictive scores along with the pre-specified sensitivity parameter are used to define an imputing set. The proposed approach is expected to be robust against mis-specifications of the selection model and the sensitivity parameter since the selection model and the sensitivity parameter are not directly used to impute missing covariate values. A simulation study is conducted to study the performance of the proposed approach when MNAR is induced by Heckman's selection model. Simulation results show the proposed approach can produce plausible regression coefficient estimates. The proposed sensitivity analysis approach is also applied to evaluate the impact of MNAR on the relationship between post-operative outcomes and incomplete pre-operative Hemoglobin A1c level for patients who underwent carotid intervetion for advanced atherosclerotic disease.

Apixaban for Treatment of Atrial Fibrillation and Venous Thromboembolism After Lung Transplantation.

INTRODUCTION: Guidelines recommend the use of direct oral anticoagulation therapy over warfarin for the treatment of venous thromboembolism and atrial fibrillation. However, there is uncertainty and a lack of data supporting the safety and efficacy of anticoagulation therapy in lung transplant recipients. Additionally, there are unique considerations for this population, such as labile renal function and drug interactions. PROJECT AIMS: The objective of this program evaluation was to evaluate the safety and efficacy of apixaban therapy for atrial fibrillation and venous thromboembolism in lung transplant recipients. DESIGN: Medical records of all adult lung transplant recipients who received apixaban for atrial fibrillation or venous thromboembolism treatment between January 1, 2018, and August 31, 2020 were retrospectively reviewed. Safety was evaluated by the incidence of bleeding. Efficacy was evaluated by the recurrence of blood clots or the incidence of stroke. RESULTS: A total of 134 recipients were included in the review. Thromboembolisms occurred in 14 recipients (10%), and none experienced a stroke. Bleeding occurred in 12 recipients (9%). CONCLUSIONS: The results of this evaluation were similar to those seen in smaller studies of the safety and efficacy of direct oral anticoagulation therapy for the treatment of atrial fibrillation or venous thromboembolism in lung transplant recipients, especially in recipients taking interacting azole antifungals. Prospective, comparative studies are needed to confirm these findings.

Correlation between prehospital and in-hospital hypotension and outcomes after traumatic brain injury.

BACKGROUND AND OBJECTIVE: Hypotension has a powerful effect on patient outcome after traumatic brain injury (TBI). The relative impact of hypotension occurring in the field versus during early hospital resuscitation is unknown. We evaluated the association between hypotension and mortality and non-mortality outcomes in four cohorts defined by where the hypotension occurred [neither prehospital nor hospital, prehospital only, hospital only, both prehospital and hospital]. METHODS: Subjects ≥10 years with major TBI were included. Standard statistics were used for unadjusted analyses. We used logistic regression, controlling for significant confounders, to determine the adjusted odds (aOR) for outcomes in each of the three cohorts. RESULTS: Included were 12,582 subjects (69.8% male; median age 44 (IQR 26-61). Mortality by hypotension status: No hypotension: 9.2% (95%CI: 8.7-9.8%); EMS hypotension only: 27.8% (24.6-31.2%); hospital hypotension only: 45.6% (39.1-52.1%); combined EMS/hospital hypotension 57.6% (50.0-65.0%); (p < 0.0001). The aOR for death reflected the same progression: 1.0 (reference-no hypotension), 1.8 (1.39-2.33), 2.61 (1.73-3.94), and 4.36 (2.78-6.84), respectively. The proportion of subjects having hospital hypotension was 19.0% (16.5-21.7%) in those with EMS hypotension compared to 2.0% (1.8-2.3%) for those without (p < 0.0001). Additionally, the proportion of patients with TC hypotension was increased even with EMS "near hypotension" up to an SBP of 120 mmHg [(aOR 3.78 (2.97, 4.82)]. CONCLUSION: While patients with hypotension in the field or on arrival at the trauma center had markedly increased risk of death compared to those with no hypotension, those with prehospital hypotension that was not resolved before hospital arrival had, by far, the highest odds of death. Furthermore, TBI patients who had prehospital hypotension were five times more likely to arrive hypotensive at the trauma center than those who did not. Finally, even "near-hypotension" in the field was strongly and independently associated the risk of a hypotensive hospital arrival (<90 mmHg). These findings are supportive of the prehospital guidelines that recommend aggressive prevention and treatment of hypotension in major TBI.

Impact of pneumoperitoneum pressure during laparoscopic hysterectomy: A randomized controlled trial.

OBJECTIVE: Minimally invasive hysterectomy is a commonly performed gynecologic procedure with associated postoperative pain managed with opioid medications. Uncontrolled postoperative pain leads to increased opioid use/abuse, longer hospital stays, increase in healthcare visits, and may negatively affect patient satisfaction. Current data suggests that reduced pneumoperitoneum insufflation pressure during laparoscopic surgery may impact postoperative pain. Given the current opioid epidemic, surgeons are proactively finding ways to reduce postoperative pain. It is unclear how reduced pneumoperitoneum pressure impacts the surgeon. We investigated the impact of reduced pneumoperitoneum insufflation pressure on surgeon satisfaction. STUDY DESIGN: This was a pilot, double-blinded, randomized controlled trial from March 2020 to July 2021 comparing pneumoperitoneum pressure of 15 mmHg to reduced pressures of 12 mmHg and 10 mmHg during laparoscopic hysterectomy. RESULTS: A total of 40 patients were randomized (13 - 15 mmHg, 13 - 12 mmHg, and 14 - 10 mmHg). The primary outcome was surgeon satisfaction. Secondary outcomes included patient satisfaction, operative time, blood loss, postoperative pain, opioid usage, and discharge timing. There were no differences in baseline demographics or perioperative characteristics. Surgeon satisfaction was negatively impacted with lower pneumoperitoneum pressures greatest with 10 mmHg, including overall satisfaction (p =.01), overall effect of the pneumoperitoneum (p =.04), and quality of visualization (p =.01). There was an apparent although not statistically significant difference in operative time (p =.06) and blood loss (p =.054). There was no difference in patient satisfaction, postoperative pain scores, opioid usage, or time to discharge. CONCLUSION(S): Reduced pneumoperitoneum insufflation pressure during laparoscopic hysterectomy negatively impacted surgeon satisfaction with a trend towards longer operative times and greater blood loss, and did not positively impact patient satisfaction, postoperative pain, opioid demand, or discharge timing.

Long-term stability of reactor microbiome through bioaugmentation with Alcaligenes aquatilis AS1 promotes nitrogen removal of piggery wastewater.

Bioaugmentation is considered as an attractive method for nitrogen removal in water treatment, but its effectiveness in actual high-strength piggery wastewater has not been adequately verified and the mechanism of bioaugmentation in actual wastewater treatment system is not very clear especially from the perspectives of microbial communities and functional genes. This study investigated the mechanisms of a heterotrophic nitrifying-aerobic denitrifying strain Alcaligenes aquatilis AS1 in the bioaugmentation of continuous biological nitrogen removal of actual piggery wastewater at laboratory scale. The addition of strain AS1 significantly improved the nitrogen removal efficiency (more than 95% of NH4+-N and 75% of TN were removed) and raised the activated sludge resistance to shock loading. AS1 addition also significantly shifted the microbiota structure and interactions among microbial networks were enhanced to obtain the stable bacterial communities. Moreover, strain AS1 achieved effective proliferation and long-term colonization in activated sludge with a relative abundance of genus Alcaligenes more than 70% during the whole operation process and played a dominant role in biological nitrogen removal, while different genera were respectively enriched and involved in pollutants removal at different stages in the control group. In addition, the abundances of most functional genes involved in carbon (C) degradation, carbon fixation and nitrogen (N), phosphorus (P), sulfur (S) cycling in activated sludge were significantly increased in reactor AS1, indicating that strain AS1 not only relied on its unique C and N metabolic activities, but also recruited microorganisms with diverse functions to jointly remove pollutants in wastewater, which could be a common bioaugmentation mechanism in open reactors. This study proves the promising application prospect of strain AS1 in the treatment of high-strength piggery wastewater and shows great importance for guiding bioaugmentation application of functional strains in practical wastewater treatment systems.

Risk factors associated with venous thromboembolism in laparoscopic surgery in non-obese patients with benign disease.

INTRODUCTION: Few studies have focused on intraoperative positioning as a risk factor for venous thromboembolism (VTE). Positioning that places the legs in a dependent position may be a risk factor. We theorized that the reverse-Trendelenburg position specifically would increase the risk of postoperative VTE. METHODS AND PROCEDURES: 374,017 subjects undergoing laparoscopic surgery in the 2015-2018 NSQIP database were included. Diagnosis of cancer and BMI ≥ 30 were excluded. Subjects were grouped based on positioning: reverse-Trendelenburg (RT), supine (S), and Trendelenburg (T). RESULTS: The RT, S, and T groups consisted of 117,887, 66,511, and 189,619 subjects, respectively. Overall median BMI was 25.7, and 82.8% of subjects were non-smokers. VTE within 30 days postoperative was seen in 0.25% RT, 0.23% S, and 0.4% T (p < 0.0001); 30-day mortality was 0.34% RT, 0.25% S, and 0.19% T (p < 0.0001). After adjusting for potential confounders and other risk factors, RT position was associated with a lower risk of VTE compared to S (OR 1.49 with 95% CI 1.16, 1.93) and T (OR 1.34 with 95% CI 1.15, 1.56) positions. VTE risk was significantly different across the three groups (p = 0.0001). Inpatient procedures had a higher VTE risk vs outpatient (OR 2.49 with 95% CI 2.10, 2.95). Increasing operative time was associated with higher VTE risk [4th (> 106 min) vs 1st (≤ 40 min) quartiles (OR 3.54 with 95% CI 2.79, 4.48)]. CONCLUSIONS: Among other risk factors, inpatient procedures and longer operative times are associated with higher VTE risk in laparoscopic surgery performed for benign disease in non-obese patients. The risk was significantly different across the three positioning groups with lowest risk in the RT group and highest risk in the S group.

The Effect of Patient Positioning on Ureteral Efflux During Intraoperative Cystoscopy: A Randomized Controlled Trial.

STUDY OBJECTIVE: To identify the relationship between patient position during surgery and time to confirmation of ureteral patency on cystoscopy. DESIGN: Randomized controlled trial. SETTING: Academic tertiary care medical center. PATIENTS OR PARTICIPANTS: A total of 91 adult women undergoing laparoscopic (either conventional or robotic) hysterectomy between February 2021 and February 2022 were randomized to intervention (n = 45) or control (n = 46). Exclusion criteria included known kidney disease or urinary tract anomaly, current ureteral stent, pregnancy, malignancy, and recognized intraoperative urinary tract injury. INTERVENTIONS: Subjects in the control group were placed in a 0° supine position during cystoscopy. Subjects in the intervention group were placed in a 20° angle in reverse Trendelenburg (RT) position during cystoscopy. MEASUREMENTS AND MAIN RESULTS: The primary outcome, time to confirmation of bilateral ureteral patency, was measured at the time the second ureteral jet was viewed during intraoperative cystoscopy. There was no significant difference in mean time to confirmation (66.5 seconds in supine vs 67 seconds in RT, p = .2) nor in total cystoscopy time (111 seconds in supine vs 104.5 seconds in RT, p = .39). There were no significant differences in need for alternative modalities to aid in ureteral efflux visualization, delayed diagnosis of ureteric injury, and operative time. RT position seemed to have reduced the time to confirmation for the small group of patients with longer confirmation time (>120 seconds). CONCLUSION: RT position does not change time to confirmation of bilateral ureteral patency compared with supine position. However, there may be a benefit in position change if time to confirmation is >120 seconds.

Carfilzomib versus rituximab for treatment of de novo donor-specific antibodies in lung transplant recipients.

INTRODUCTION: De novo donor-specific antibodies (DSAs) increase the risk of chronic lung allograft dysfunction (CLAD) in lung transplant recipients (LTRs). Both carfilzomib (CFZ) and rituximab (RTX) lower the mean fluorescent intensity (MFI) of DSAs, but comparative data are lacking. We compared CLAD-free survival and the degree and duration of DSA depletion after treatment of LTRs with CFZ or RTX. METHODS: LTRs that received CFZ or RTX for DSA depletion between 08/01/2015 and 08/31/2020 were included. The primary outcome was CLAD-free survival. Secondary outcomes were change in MFI at corresponding loci within 6 months of treatment (ΔMFI), time to DSA rebound, and change in % predicted FEV1 6 months after treatment (ΔFEV1). RESULTS: Forty-four LTRs were identified, 7 of whom had ≥2 drug events; therefore, 53 drug events were divided into 2 groups, CFZ (n = 17) and RTX (n = 36). Use of plasmapheresis, immunoglobulin, and mycophenolate augmentation was equivalent in both groups. CLAD-free survival with a single RTX event was superior to that after ≥2 drug events (p = 0.001) but comparable to that with a single CFZ event (p = 0.399). Both drugs significantly lowered the MFI at DQ locus, and the median ΔMFI was comparable. Compared to the RTX group, the CFZ group had a shorter median interval to DSA rebound (p = 0.015) and a lower ΔFEV1 at 6 months (p = 0.014). CONCLUSION: Although both CFZ and RTX reduced the MFI of circulating DSAs, RTX prolonged the time to DSA rebound. Despite more pronounced improvement in FEV1 with RTX, comparable CLAD-free survival between the 2 groups suggests that both drugs offer a reasonable treatment strategy for DSAs in LTRs.

Optimal Out-of-Hospital Blood Pressure in Major Traumatic Brain Injury: A Challenge to the Current Understanding of Hypotension.

STUDY OBJECTIVE: Little is known about the out-of-hospital blood pressure ranges associated with optimal outcomes in traumatic brain injuries (TBI). Our objective was to evaluate the associations between out-of-hospital systolic blood pressure (SBP) and multiple hospital outcomes without assuming any predefined thresholds for hypotension, normotension, or hypertension. METHODS: This was a preplanned secondary analysis from the Excellence in Prehospital Injury Care (EPIC) TBI study. Among patients (age ≥10 years) with major TBIs (Barell Matrix type 1 and/or Abbreviated Injury Scale-head severity ≥3) and lowest out-of-hospital SBPs of 40 to 299 mmHg, we utilized generalized additive models to summarize the distributions of various outcomes as smoothed functions of SBP, adjusting for important and significant confounders. The subjects who were enrolled in the study phase after the out-of-hospital TBI guideline implementation were used to validate the models developed from the preimplementation cohort. RESULTS: Among 12,169 included cases, the mortality model revealed 3 distinct ranges: (1) a monotonically decreasing relationship between SBP and the adjusted probability of death from 40 to 130 mmHg, (2) lowest adjusted mortality from 130 to 180 mmHg, and (3) rapidly increasing mortality above 180 mmHg. A subanalysis of the cohorts with isolated TBIs and multisystem injuries with TBIs revealed SBP mortality patterns that were similar to each other and to that of the main analysis. While the specific SBP ranges varied somewhat for the nonmortality outcomes (hospital length of stay, ICU length of stay, discharge to skilled nursing/inpatient rehabilitation, and hospital charges), the patterns were very similar to that of mortality. In each model, validation was confirmed utilizing the postimplementation cohort. CONCLUSION: Optimal adjusted mortality was associated with a surprisingly high SBP range (130 to 180 mmHg). Below this level, there was no point or range of inflection that would indicate a physiologically meaningful threshold for defining hypotension. Nonmortality outcomes showed very similar patterns. These findings highlight how sensitive the injured brain is to compromised perfusion at SBP levels that, heretofore, have been considered adequate or even normal. While the study design does did not allow us to conclude that the currently recommended treatment threshold (<90 mmHg) should be increased, the findings imply that the definition of hypotension in the setting of TBI is too low. Randomized trials evaluating treatment levels significantly higher than 90 mmHg are needed.