Iron Chelation in Soil: Scalable Biotechnology for Accelerating Carbon Dioxide Removal by Enhanced Rock Weathering.

Enhanced rock weathering (EW) is an emerging atmospheric carbon dioxide removal (CDR) strategy being scaled up by the commercial sector. Here, we combine multiomics analyses of belowground microbiomes, laboratory-based dissolution studies, and incubation investigations of soils from field EW trials to build the case for manipulating iron chelators in soil to increase EW efficiency and lower costs. Microbial siderophores are high-affinity, highly selective iron (Fe) chelators that enhance the uptake of Fe from soil minerals into cells. Applying RNA-seq metatranscriptomics and shotgun metagenomics to soils and basalt grains from EW field trials revealed that microbial communities on basalt grains significantly upregulate siderophore biosynthesis gene expression relative to microbiomes of the surrounding soil. Separate in vitro laboratory incubation studies showed that micromolar solutions of siderophores and high-affinity synthetic chelator (ethylenediamine-N,N'-bis-2-hydroxyphenylacetic acid, EDDHA) accelerate EW to increase CDR rates. Building on these findings, we develop a potential biotechnology pathway for accelerating EW using the synthetic Fe-chelator EDDHA that is commonly used in agronomy to alleviate the Fe deficiency in high pH soils. Incubation of EW field trial soils with potassium-EDDHA solutions increased potential CDR rates by up to 2.5-fold by promoting the abiotic dissolution of basalt and upregulating microbial siderophore production to further accelerate weathering reactions. Moreover, EDDHA may alleviate potential Fe limitation of crops due to rising soil pH with EW over time. Initial cost-benefit analysis suggests potassium-EDDHA could lower EW-CDR costs by up to U.S. $77 t CO2 ha-1 to improve EW's competitiveness relative to other CDR strategies.

Mode of Fixation and Survivorship in Primary Total Knee Arthroplasty in the American Joint Replacement Registry.

BACKGROUND: A recent rapid increase in cementless total knee arthroplasty (TKA) has been noted in the American Joint Replacement Registry (AJRR). The purpose of our study was to compare TKA survivorship based on the mode of fixation reported to the AJRR in the Medicare population. METHODS: Primary TKAs from Medicare patients submitted to AJRR from 2012 to 2022 were analyzed. The Medicare and AJRR databases were merged. Cox regression stratified by sex compared revision outcomes (all-cause, infection, mechanical loosening, and fracture) for cemented, cementless, and hybrid fixation, controlling for age and the Charlson comorbidity index (CCI). RESULTS: A total of 634,470 primary TKAs were analyzed. Cementless TKAs were younger (71.8 versus 73.1 years, P < .001) than cemented TKAs and more frequently utilized in men (8.2 versus 5.8% women, P < .001). Regional differences were noted, with cementless fixation more common in the Northeast (10.5%) and South (9.2%) compared to the West (4.4%) and Midwest (4.3%) (P < .001). No significant differences were identified in all-cause revision rates in men or women ≥ 65 for cemented, cementless, or hybrid TKA after adjusting for age and CCI. Significantly lower revision for fracture was identified for cemented compared to cementless and hybrid fixation in women ≥ 65 after adjusting for age and CCI (P = .0169). CONCLUSIONS: No survivorship advantage for all-cause revision was noted based on the mode of fixation in men or women ≥ 65 after adjusting for age and CCI. A significantly lower revision rate for fractures was noted in women ≥ 65 utilizing cemented fixation. Cementless fixation in primary TKA should be used with caution in elderly women.

Superficial versus deep parasternal intercostal plane blocks: cadaveric evaluation of injectate spread.

BACKGROUND: Deep and superficial parasternal intercostal plane blocks provide anterior chest wall analgesia for both breast and cardiac surgery. Our primary objective of this cadaveric study was to describe the parasternal spread of deep and superficial parasternal intercostal plane blocks. Our secondary objectives were to describe needle proximity to the internal mammary artery when performing deep parasternal intercostal plane blocks, and compare lateral injectate spread and extension into the rectus sheath. METHODS: We performed ultrasound-guided deep and superficial parasternal intercostal plane blocks 2 cm from the sternum at the T3-4 interspace in four fresh frozen cadavers as described in clinical studies. RESULTS: Parasternal spread of injectate was greater with the deep parasternal intercostal plane injection than with the superficial parasternal intercostal plane injection. The internal mammary artery was ∼3 mm away from the needle trajectory in cadaver #1 and ∼5 mm from the internal mammary artery in cadaver #2. Lateral spread extended to the midclavicular line for all deep parasternal intercostal plane blocks and beyond the midclavicular line for all superficial parasternal intercostal plane blocks. Neither block extended to the rectus sheath. CONCLUSIONS: A greater number of parasternal interspaces were covered with the deep parasternal intercostal plane block than with the superficial parasternal intercostal plane block when one injection was performed at the T3-4 interspace. However, considering proximity to the internal mammary artery, and potential devastating consequences of an arterial injury, we propose that the deep parasternal intercostal plane block be classified as an advanced block and that future studies focus on optimising superficial parasternal intercostal plane parasternal spread.

Fully resorbable poly-4-hydroxybutyrate (P4HB) mesh for soft tissue repair and reconstruction: A scoping review.

Background: Poly-4-hydroxybutyrate (P4HB) is a fully resorbable, biologically-produced polymer with a strength and flexibility comparable to permanent synthetic polymers. The objective was to identify/summarize all peer-reviewed publications involving P4HB mesh. Methods: A scoping review was conducted within PubMed and included articles published through October 2022. Results: A total of n = 79 studies were identified (n = 12 in vitro/bench; n = 14 preclinical; n = 6 commentaries; n = 50 clinical). Of the clinical studies, n = 40 reported results applicable to hernia and n = 10 to plastic/reconstructive surgery and involved patients of all Centers for Disease Control (CDC) wound classes and Ventral Hernia Working Group (VHWG) grades. Conclusion: P4HB mesh provides long-term hernia repair strength and exhibits promising clinical outcomes beyond its resorption period. Future studies should include randomized controlled trials comparing P4HB to other biomaterials, as well as optimal patient selection, operative technique, long-term outcomes, minimization of potential mesh-related complications, and potential contraindications/complications for P4HB in hernia/abdominal wall reconstruction.

Anesthetic Management and Deep Sedation After Emergence From General Anesthesia: A Retrospective Cohort Study.

BACKGROUND: Residual deep sedation during anesthesia recovery may predict postoperative complications. We examined the incidence and risk factors for deep sedation after general anesthesia. METHODS: We retrospectively reviewed health records of adults who underwent procedures with general anesthesia and were admitted to the postanesthesia care unit from May 2018 to December 2020. Patients were dichotomized by Richmond Agitation-Sedation Scale (RASS) score: ≤-4 (deeply sedated/unarousable) or ≥-3 (not deeply sedated). Anesthesia risk factors for deep sedation were assessed with multivariable logistic regression. RESULTS: Of the 56,275 patients included, 2003 had a RASS ≤-4 (35.6 [95% CI, 34.1-37.2] cases per 1000 anesthetics administered). On adjusted analyses, the likelihood of a RASS ≤-4 increased when more soluble halogenated anesthetics were used. Compared with desflurane without propofol, the odds ratio (OR [95% CI]) for a RASS ≤-4 was higher with sevoflurane (1.85 [1.45-2.37]) and isoflurane (4.21 [3.29-5.38]) without propofol. Compared with desflurane without propofol, the odds of a RASS ≤-4 further increased with use of desflurane-propofol (2.61 [1.99-3.42]), sevoflurane-propofol (4.20 [3.28-5.39]), isoflurane-propofol (6.39 [4.90-8.34]), and total intravenous anesthesia (2.98 [2.22-3.98]). A RASS ≤-4 was also more likely with the use of dexmedetomidine (2.47 [2.10-2.89]), gabapentinoids (2.17 [1.90-2.48]), and midazolam (1.34 [1.21-1.49]). Deeply sedated patients discharged to general care wards had higher odds of opioid-induced respiratory complications (2.59 [1.32-5.10]) and higher odds of naloxone administration (2.93 [1.42-6.03]). CONCLUSIONS: Likelihood of deep sedation after recovery increased with intraoperative use of halogenated agents with higher solubility and increased further when propofol was concomitantly used. Patients who experience deep sedation during anesthesia recovery have an increased risk of opioid-induced respiratory complications on general care wards. These findings may be useful for tailoring anesthetic management to reduce postoperative oversedation.

Association of Indication for Hospitalization With Subsequent Amyloid Positron Emission Tomography and Magnetic Resonance Imaging Biomarkers.

BACKGROUND: Hospitalization in older age is associated with accelerated cognitive decline, typically preceded by neuropathologic changes. We assess the association between indication for hospitalization and brain neurodegeneration. METHODS: Included were participants from the Mayo Clinic Study of Aging, a population-based longitudinal study, with ≥1 brain imaging available in those older than 60 years of age between 2004 and 2017. Primary analyses used linear mixed-effects models to assess association of hospitalization with changes in longitudinal trajectory of cortical thinning, amyloid accumulation, and white matter hyperintensities (WMH). Additional analyses were performed with imaging outcomes dichotomized (normal vs abnormal) using Cox proportional hazards regression. RESULTS: Of 2 480 participants, 1 966 had no hospitalization and 514 had ≥1 admission. Hospitalization was associated with accelerated cortical thinning (annual slope change -0.003 mm [95% confidence interval (CI) -0.005 to -0.001], p = .002), but not amyloid accumulation (0.003 [95% CI -0.001 to 0.006], p = .107), or WMH increase (0.011 cm3 [95% CI -0.001 to 0.023], p = .062). Interaction analyses assessing whether trajectory changes are dependent on admission type (medical vs surgical) found interactions for all outcomes. While surgical hospitalizations were not, medical hospitalizations were associated with accelerated cortical thinning (-0.004 mm [95% CI -0.008 to -0.001, p = .014); amyloid accumulation (0.010, [95% CI 0.002 to 0.017, p = .011), and WMH increase (0.035 cm3 [95% CI 0.012 to 0.058, p = .006). Hospitalization was not associated with developing abnormal cortical thinning (p = .407), amyloid accumulation (p = .596), or WMH/infarctions score (p = .565). CONCLUSIONS: Medical hospitalizations were associated with accelerated cortical thinning, amyloid accumulation, and WMH increases. These changes were modest and did not translate to increased risk for crossing the abnormality threshold.

Surgical site infections during the COVID-19 era: A retrospective, multicenter analysis.

BACKGROUND: Surgical site infections (SSIs) are an undesired perioperative outcome. Recent studies have shown increases in hospital acquired infections during the coronavirus disease 2019 (COVID-19) pandemic. The objective of this study was to evaluate postoperative SSIs in the COVID-19-era compared to a historical cohort at a large, multicenter, academic institution. METHODS: A retrospective review of all patients who underwent National Health and Safety Network (NHSN) inpatient surgical procedures between January 1, 2018 and December 31, 2020. Patients from the COVID-19-era (March-December 2020) were compared and matched 1:1 with historical controls (2018/2019) utilizing the standardized infection ratio (SIR) to detect difference. RESULTS/DISCUSSION: During the study period, 29,904 patients underwent NHSN procedures at our institution. When patients from the matched cohort (2018/2019) were compared to the COVID-19-era cohort (2020), a decreased risk of SSI was observed following colorectal surgery (RR = 0.94, 95% CI [0.65, 1.37], P = .76), hysterectomy (RR = 0.88, 95% CI [0.39, 1.99], P = .75), and knee prothesis surgery (RR = 0.95, 95% CI [0.52, 1.74], P = .88), though not statistically significant. An increased risk of SSI was observed following hip prosthesis surgery (RR 1.09, 95% CI [0.68, 1.75], P = .72), though not statistically significant. CONCLUSIONS: The risk of SSI in patients who underwent NHSN inpatient surgical procedures in 2020 with perioperative COVID-19 precautions was not significantly different when compared to matched controls at our large, multicenter, academic institution.

Intermittent Cerebrospinal Leak After Inadvertent Dural Puncture During Epidural Catheter Placement for Postoperative Analgesia.

Regional anesthesia is being used more frequently in pediatric anesthesia practice, including the perioperative care of neonates and infants. Adverse effects may be encountered during epidural needle placement, with catheter advancement, or subsequently during infusion of local anesthetic agents. We present the rare occurrence of a persistent cerebrospinal fluid (CSF) leak following inadvertent dural puncture (wet tap) during attempted placement of an epidural catheter in a 6-year-old child. Potential adverse effects of epidural anesthesia in children are discussed, and options for treatment of a persistent CSF leak after inadvertent dural puncture are reviewed.

Association of blood pressure variability with short- and long-term cognitive outcomes in patients with critical illness.

BACKGROUND: Blood pressure variability (BPV), a modifiable risk factor, can compromise cerebral perfusion in critically ill patients. We studied the association between BPV in the intensive care unit (ICU) and short- and long-term cognitive outcomes. METHODS: All patients were ≥50 years old. The short-term cognitive end points were delirium and depressed alertness without delirium. The long-term outcome was change in the slope of longitudinal cognitive scores. Primary BPV measure was average real variability (ARV) of systolic blood pressure. Associations were assessed with multivariable multinominal logistic regression and linear mixed effects models. RESULTS: Of 794 patients (1130 admissions) 185 developed delirium and 274 developed depressed alertness. There was a dose-response association of 24-h systolic ARV with delirium (adjusted OR, 95% CI 2.15 per 5 mm Hg increase, 1.31-3.06, P < 0.017) and with depressed alertness (OR 1.89, 95% CI 1.18-3.03, P < 0.008). For 371 patients with available longitudinal cognitive scores, the decline in cognitive trajectory was accelerated after discharge (annual change OR -0.097, 95% CI -0.122 to -0.073). This acceleration increased with delirium (additional decline -0.132 [-0.233 to 0.030], P = 0.011). We found no significant association between BPV and post-ICU cognitive trajectory. CONCLUSIONS: BPV was associated with increased likelihood of delirium in the ICU. Delirium, but not BPV, was associated with long-term cognitive decline.

Hemodynamics in Patients With Pheochromocytoma or Paraganglioma Undergoing Non-neuroendocrine Operations.

INTRODUCTION: Surgical resection of pheochromocytoma and paraganglioma (PPGL) may be associated with excessive hemodynamic variability. Whether hemodynamic variability occurs in patients with undiagnosed PPGL undergoing unrelated, non-neuroendocrine, operations is unknown. METHODS: We identified patients who underwent non-neuroendocrine surgical procedures up to 5 y before pathologic diagnosis of PPGL. For each PPGL, two non-PPGL patients were matched based on sex, age, type, and year of operation. Electronic medical records were reviewed for intraoperative blood pressures, heart rates, and hemodynamic variability was assessed with range (maximum-minimum), standard deviation, coefficient of variation, and average real variability. RESULTS: Thirty-seven PPGL patients underwent operations preceding the diagnosis of PPGL: 25 pheochromocytomas, 11 paragangliomas, and one metastatic pheochromocytoma. Median interquartile range tumor size at diagnosis was 35 mm (23 to 60). The time from index operation to PPGL diagnosis was ≤12 mo in 21 (56.8%) patients. In 23 (62.2%) patients, the subsequently diagnosed PPGL was functional. Fifteen (40.5%) PPGL and 20 (27.0%) control patients were preoperatively treated for hypertension (P = 0.149). Maximum intraoperative systolic BP was >180 mmHg for 4 (10.8%) PPGL patients and 3 (4.1%) controls (P = 0.219). Two PPGL patients had intraoperative systolic BP >230 mmHg. No significant differences were found with all other measures of intraoperative hemodynamic variability. Similarly, in secondary analysis there was no significant difference in intraoperative hemodynamic variability between biochemically active PPGL and their respective controls. CONCLUSIONS: Patients with undiagnosed PPGL undergoing a wide variety of non-neuroendocrine operations had intraoperative hemodynamic variability comparable to non-PPGL patients undergoing the same type of procedures.

Photobacterium damsela Necrotizing Fasciitis of the Arm.

Photobacterium damsela is a gram-negative bacterium that is known to cause infection, most commonly in marine animals and rarely in humans. Photobacterium damsela typically results in skin and soft tissue infections in humans and has been associated with necrotizing fasciitis in several case reports. After an initially benign presentation, P damsela necrotizing fasciitis often progresses rapidly to multiorgan failure and death. Here, we present a fatal case of P damsela necrotizing fasciitis after a minor cut while scaling a fish with a discussion of current literature and treatment strategies.

Vascular Response Toward an Absorbable Sirolimus-eluting Polymeric Scaffold for Vascular Application in a Model of Normal Porcine Carotid Arteries.

BACKGROUND: Fully absorbable polymeric scaffolds, as a potential alternative to permanent metallic stents, are entering the clinical field. The aim of this study is to assess the in vivo biocompatibility of a novel Sirolimus-eluting (SIR) absorbable scaffold based on poly(L-lactide) (PLLA) and poly(4-hydroxybutyrate) (P4HB) for interventional application. METHODS: Absorbable PLLA/P4HB scaffolds either loaded with SIR coating or unloaded scaffolds were implanted interventionally into common carotid arteries of 14 female. Bare metal stents (BMS) served as control. Peroral dual anti-platelet therapy was administered throughout the study. Stented common carotid arteries segments were explanted after 4 weeks, and assessed histomorphometrically. RESULTS: The absorbable scaffolds showed a decreased residual lumen area and higher stenosis after 4 weeks (PLLA/P4HB: 6.56 ± 0.41 mm² and 37.56 ± 4.67%; SIR-PLLA/P4HB: 6.90 ± 0.58 mm² and 35.60 ± 3.15%) as compared to BMS (15.29 ± 1.86 mm² and 7.65 ± 2.27%). Incorporation of SIR reduced the significantly higher inflammation of unloaded scaffolds however not to a level compared to bare metal stent (PLLA/P4HB: 1.20 ± 0.19; SIR-PLLA/P4HB: 0.96 ± 0.24; BMS: 0.54 ± 0.12). In contrast, the BMS showed a slightly elevated vascular injury score (0.74 ± 0.15), as compared to the PLLA/P4HB (0.54 ± 0.20) and the SIR-PLLA/P4HB (0.48 ± 0.15) groups. CONCLUSION: In this preclinical model, the new absorbable polymeric (SIR-) scaffolds showed similar technical feasability and safety for vascular application as the permanent metal stents. The higher inflammatory propensity of the polymeric scaffolds was slightly reduced by SIR-coating. A smaller strut thickness of the polymeric scaffolds might have been a positive effect on tissue ingrowth between the struts and needs to be addressed in future work on the stent design.

Postoperative Apnea in a Neonate Following an Epidural Bolus Dose Through a High Thoracic Epidural Catheter.

Regional anesthesia is being used more frequently in the practice of pediatric anesthesia including neonates and infants. While generally safe and effective, adverse effects may occur related to catheter placement or its subsequent use. We present the rare occurrence of high motor blockade with apnea following the administration of a bolus dose of the local anesthetic agent, 2-chloroprocaine, into the thoracic epidural catheter of a 4-week-old, 2.2-kg former premature neonate. The patient had an epidural catheter that had been threaded from the caudal space to the thoracic level to provide analgesia following an abdominal surgical procedure. Subsequent investigation with a standard chest radiograph revealed a higher than intended placement of the epidural catheter (T4 instead of T8-10) which resulted in a transient high motor blockade with apnea. The epidural infusion was discontinued and assisted ventilation was provided by bag-valve-mask ventilation. Immediately, the heart rate and oxygen saturation returned to baseline values, and within 5 min the patient became more active, spontaneous ventilation resumed, and a strong cry was noted. The epidural catheter was removed and the remainder of the postoperative course was unremarkable. Adverse effects of epidural anesthesia in neonates are discussed and options for identifying the correct placement of a thoracic epidural catheter are reviewed.

Immune Function following Major Spinal Surgery and General Anesthesia.

There are reported differences in the effects that general anesthetics may have on immune function after minor surgery. To date, there are no prospective trials comparing total intravenous anesthesia (TIVA) with a volatile agent-based technique and its effects on immune function after major spinal surgery in adolescents. Twenty-six adolescents undergoing spinal fusion were randomized to receive TIVA with propofol-remifentanil or a volatile agent-based technique with desflurane-remifentanil. Immune function measures were based on the antigen-presenting and cytokine production capacity, and relative proportions of cell populations. Overall characteristics of the two groups did not differ in terms of perioperative times, hemodynamics, or fluid shifts, but those treated with propofol had lower bispectral index values. Experimental groups had relatively high baseline interleukin-10 values, but both showed a significant inflammatory response with similar changes in their respective immune functions. This included a shift toward a granulocytic predominance; a transient reduction in monocyte markers with significant decrease in antigen-presenting capacity and cytokine production capacity. Anesthetic choice does not appear to differentially impact immune function, but exposure to anesthetics and surgical trauma results in reproducibly measurable suppression of both innate and adaptive immunity in adolescents undergoing posterior spinal fusion. The magnitude of this suppression was modest when compared with pediatric and adult patients with critical illnesses. This study highlighted the need to evaluate immune function in a broader population of surgical patients with higher severity of illness.

Evidence-based aerosol clearance times in a healthcare environment.

BACKGROUND: As researchers race to understand the nature of COVID-19 transmission, healthcare institutions must treat COVID-19 patients while also safeguarding the health of staff and other patients. One aspect of this process involves mitigating aerosol transmission of the SARS-CoV2 virus. The U.S. Centers for Disease Control and Prevention (CDC) provides general guidance on airborne contaminant removal, but directly measuring aerosol clearance in clinical rooms provides empirical evidence to guide clinical procedure. AIM: We present a risk-assessment approach to empirically measuring and certifying the aerosol clearance time (ACT) in operating and procedure rooms to improve hospital efficiency while also mitigating the risk of nosocomial infection. METHODS: Rooms were clustered based on physical and procedural parameters. Sample rooms from each cluster were randomly selected and tested by challenging the room with aerosol and monitoring aerosolized particle concentration until 99.9% clearance was achieved. Data quality was analysed and aerosol clearance times for each cluster were determined. FINDINGS: Of the 521 operating and procedure rooms considered, 449 (86%) were issued a decrease in clearance time relative to CDC guidance, 32 (6%) had their clearance times increased, and 40 (8%) remained at guidance. The average clearance time change of all rooms assessed was a net reduction of 27.8%. CONCLUSION: The process described here balances the need for high-quality, repeatable data with the burden of testing in a functioning clinical setting. Implementation of this approach resulted in a reduction in clearance times for most clinical rooms, thereby improving hospital efficiency while also safeguarding patients and staff.

The effects of shoulder arthroscopy on ultrasound image quality of the interscalene brachial plexus: a pre-procedure vs post-procedure comparative study.

BACKGROUND: Fluid extravasation from the shoulder compartment and subsequent absorption into adjacent soft tissue is a well-documented phenomenon in arthroscopic shoulder surgery. We aimed to determine if a qualitative difference in ultrasound imaging of the interscalene brachial plexus exists in relation to the timing of performing an interscalene nerve block (preoperative or postoperative). METHODS: This single-center, prospective observational study compared pre- and postoperative interscalene brachial plexus ultrasound images of 29 patients undergoing shoulder arthroscopy using a pretest-posttest methodology where individual patients served as their own controls. Three fellowship-trained regional anesthesiologists evaluated image quality and confidence in performing a block for each ultrasound scan using a five-point Likert scale. The association of image quality with age, gender, BMI, duration of surgery, obstructive sleep apnea, and volume of arthroscopic irrigation fluid were analyzed as secondary outcomes. RESULTS: Aggregate preoperative mean scores in quality of ultrasound visualization were higher than postoperative scores (preoperative 4.5 vs postoperative 3.8; p < .001), as was confidence in performing blockade based upon the imaging (preoperative 4.8 vs postoperative 4.2; p < .001). Larger BMI negatively affected visualization of the brachial plexus in the preoperative period (p < 0.05 for both weight categories). Patients with intermediate-high risk or confirmed obstructive sleep apnea had lower aggregate postoperative mean scores compared to the low-risk group for both ultrasound visualization (3.4 vs 4.0; p < .05) and confidence in block performance (3.8 vs 4.4; p < .05). CONCLUSION: Due to the potential reduction of ultrasound visualization of the interscalene brachial plexus after shoulder arthroscopy, we advocate for a preoperative interscalene nerve block when feasible. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT03657173 ; September 4, 2018).

Exposure to anesthesia is not associated with development of α-synucleinopathies: A nested case-control study.

INTRODUCTION: Preclinical studies suggest that inhalational anesthetics may induce neuropathology changes in the nigrostriatal system, leading to development of α-synucleinopathies. We explored the role of general anesthesia in the development of Parkinson disease (PD) and other α-synucleinopathies. METHODS: All α-synucleinopathy cases in Olmsted County, Minnesota, from January 1991, to December 2010, were identified from diagnostic codes, and then reviewed for type and index date of diagnosis. Cases were matched by sex and age (±1 year) to a referent control, a resident living in Olmsted County, and free of α-synucleinopathies before the index date (year of onset of the α-synucleinopathy). Medical records of both cases and controls were reviewed for lifetime exposure to anesthesia prior to the index date. RESULTS: A total of 431 cases with clinically defined α-synucleinopathies were identified. Of these, 321 (74%) underwent 1,069 procedures under anesthesia before the diagnosis date, and in the control group, 341 (79%) underwent 986 procedures. When assessed as a dichotomous variable, anesthetic exposure was not significantly associated with α-synucleinopathies (odds ratio [OR], 0.75; 95% CI, 0.54-1.05; P=.094). No association was observed when anesthetic exposure was quantified by the number of exposures (OR, 0.64, 0.89, and  0.74, for 1, 2-3, and ≥4 exposures, respectively, compared to no exposure as the reference; P=.137) or quantified by the cumulative duration of exposure assessed as a continuous variable (OR, 1.00; 95% CI, 0.97-1.02 per 1-h increase of anesthetic exposure; P=.776). CONCLUSIONS: We did not observe a significant association between exposure to general anesthesia and risk for the development of α-synucleinopathies.

Gait Speed and Instrumental Activities of Daily Living in Older Adults After Hospitalization: A Longitudinal Population-Based Study.

BACKGROUND: Hospitalization can impair physical and functional status of older adults, but it is unclear whether these deficits are transient or chronic. This study determined the association between hospitalization of older adults and changes in long-term longitudinal trajectories of 2 measures of physical and functional status: gait speed (GS) and instrumental activities of daily living measured with Functional Activities Questionnaire (FAQ). METHOD: Linear mixed-effects models assessed the association between hospitalization (nonelective vs elective, and surgical vs medical) and outcomes of GS and FAQ score in participants (older than 60 years) enrolled in the Mayo Clinic Study of Aging who had longitudinal assessments. RESULTS: Of 4902 participants, 1879 had ≥1 hospital admission. Median GS at enrollment was 1.1 m/s. The slope of the annual decline in GS before hospitalization was -0.015 m/s. The parameter estimate (95% CI) for additional annual change in GS trajectory after hospitalization was -0.009 (-0.011 to -0.006) m/s, p < .001. The accelerated GS decline was greater for medical versus surgical hospitalizations (-0.010 vs -0.003 m/s, p = .005), and nonelective versus elective hospitalizations (-0.011 vs -0.006 m/s, p = .067). The odds of a worsening FAQ score increased on average by 4% per year. Following hospitalization, odds of FAQ score worsening further increased (multiplicative annual increase in odds ratio per year [95% CI] following hospitalization was 1.05 [1.03, 1.07], p < .001). CONCLUSIONS: Hospitalization of older adults is associated with accelerated long-term decline in GS and functional limitations, especially after nonelective admissions and those for medical indications. However, for most well-functioning participants, these changes have little clinical significance.

Transcriptome-targeted analysis of human peripheral blood-derived macrophages when cultured on biomaterial meshes.

Surgical meshes are commonly used to repair defects and support soft tissues. Macrophages (Mφs) are critical cells in the wound healing process and are involved in the host response upon foreign biomaterials. There are various commercially available permanent and absorbable meshes used by surgeons for surgical interventions. Polypropylene (PP) meshes represent a permanent biomaterial that can elicit both inflammatory and anti-inflammatory responses. In contrast, poly-4-hydroxybutyrate (P4HB) based meshes are absorbable and linked to positive clinical outcomes but have a poorly characterized immune response. This study evaluated the in vitro targeted transcriptomic response of human Mφs seeded for 48 h on PP and P4HB surgical meshes. The in vitro measured response from human Mφs cultured on P4HB exhibited inflammatory and anti-inflammatory gene expression profiles typically associated with wound healing, which aligns with in vivo animal studies from literature. The work herein provides in vitro evidence for the early transcriptomic targeted signature of human Mφs upon two commonly used surgical meshes. The findings suggest a transition from an inflammatory to a non-inflammatory phenotype by P4HB as well as an upregulation of genes annotated under the pathogen response pathway.

Brain MRI after critical care admission: A longitudinal imaging study.

PURPOSE: To investigate the association between episodes of critical care hospitalizations and delirium with structural brain changes in older adults. MATERIALS AND METHODS: We included Mayo Clinic Study of Aging participants ≥60 years old at the time of study enrollment (October 29, 2004, through September 11, 2017) with available brain MRI and 'amyloid' positron emission tomography (PET) scans. We tested the hypothesis that a) intensive care unit (ICU) admission is associated with greater cortical thinning and atrophy in entorhinal cortex, inferior temporal cortex, middle temporal cortex, and fusiform cortex (Alzheimer''s disease-signature regions); b) atrophy in hippocampus and corpus callosum; c) delirium accelerates these changes; and d) ICU admission is not associated with increased deposition of cortical amyloid. RESULTS: ICU admission was associated with cortical thinning in temporal, frontal, and parietal cortices, and decreases in hippocampal/corpus callosum volumes, but not Alzheimer''s disease-signature regions. For hippocampal volume, and 10 of 14 cortical thickness measurements, the change following ICU admission was significantly more pronounced for those who experienced delirium. ICU admission was not associated with an increased amyloid burden. CONCLUSIONS: Critical care hospitalization is associated with accelerated brain atrophy in selected brain regions, without increases in amyloid deposition, suggesting a pathogenesis based on neurodegeneration unrelated to Alzheimer''s pathway.