Effects of passive cycling on cerebrovascular reactivity in acute brain injured patients: A pilot study.

INTRODUCTION: Early mobilization benefits critically ill patients, but concerns persist, especially in neurologic intensive care unit patients with acute brain injuries. This study assesses early mobility's impact on cerebrovascular autoregulation (CA) and systemic hemodynamics. METHODS: This single-center retrospective study focused on adult neurologic intensive care unit patients undergoing passive cycle ergometry. Data were collected from December 2020 to April 2022. Physical therapists conducted sessions using a standardized protocol, monitoring mean arterial blood pressure (MAP) and intracranial pressure (ICP). The Pressure Reactivity Index (PRx) was calculated as a measure of CA. Statistical analysis included mixed models and repeated measures ANOVA. RESULTS: Eleven patients undergoing continuous physiologic monitoring and early mobility were included, primarily with subarachnoid hemorrhage or intracranial hemorrhage. Median time to protocol initiation was 4 days, with two patients discontinuing due to hemodynamic disturbances. Over a total of 11-hours of neuromonitoring data, passive cycling demonstrated a significant reduction in heart rate (HR), MAP, and ICP across different rotations per minute (RPM) settings compared to baseline. No significant alterations in PRx or cerebral perfusion pressure (CPP) were noted at various RPM levels. However, a significant difference in PRx emerged between patients who completed the protocol and those who did not, particularly at 10 RPM. DISCUSSION: This study offers preliminary insights into the impact of early mobility on CA in acute brain injured patients. While passive cycling demonstrates promise in preserving cerebral hemodynamics, its tolerability may not be uniform across all brain-injured patients. These findings highlight the need to determine optimal early mobilization timing and intensity in this population, emphasizing the necessity for larger prospective studies to validate these findings and inform clinical practice. DETAILS: This manuscript complies with all instructions to the authors. All coauthors meet the authorship requirements and have reviewed and approved the contents of the manuscript. The manuscript has not been published totally or partly, accepted for publication, or under editorial review for publication elsewhere. We have no conflicts of interest to disclose. STROBE checklist was reviewed prior to the submission of this paper. The manuscript adheres to ethical guidelines and was approved by Cleveland Clinic's institutional research board for retrospective study. There is no funding to disclose for this study.

A TrkB and TrkC partial agonist restores deficits in synaptic function and promotes activity-dependent synaptic and microglial transcriptomic changes in a late-stage Alzheimer's mouse model.

INTRODUCTION: Tropomyosin related kinase B (TrkB) and C (TrkC) receptor signaling promotes synaptic plasticity and interacts with pathways affected by amyloid beta (Aß) toxicity. Upregulating TrkB/C signaling could reduce Alzheimer's disease (AD)-related degenerative signaling, memory loss, and synaptic dysfunction. METHODS: PTX-BD10-2 (BD10-2), a small molecule TrkB/C receptor partial agonist, was orally administered to aged London/Swedish-APP mutant mice (APPL/S) and wild-type controls. Effects on memory and hippocampal long-term potentiation (LTP) were assessed using electrophysiology, behavioral studies, immunoblotting, immunofluorescence staining, and RNA sequencing. RESULTS: In APPL/S mice, BD10-2 treatment improved memory and LTP deficits. This was accompanied by normalized phosphorylation of protein kinase B (Akt), calcium-calmodulin-dependent kinase II (CaMKII), and AMPA-type glutamate receptors containing the subunit GluA1; enhanced activity-dependent recruitment of synaptic proteins; and increased excitatory synapse number. BD10-2 also had potentially favorable effects on LTP-dependent complement pathway and synaptic gene transcription. DISCUSSION: BD10-2 prevented APPL/S/Aß-associated memory and LTP deficits, reduced abnormalities in synapse-related signaling and activity-dependent transcription of synaptic genes, and bolstered transcriptional changes associated with microglial immune response. HIGHLIGHTS: Small molecule modulation of tropomyosin related kinase B (TrkB) and C (TrkC) restores long-term potentiation (LTP) and behavior in an Alzheimer's disease (AD) model. Modulation of TrkB and TrkC regulates synaptic activity-dependent transcription. TrkB and TrkC receptors are candidate targets for translational therapeutics. Electrophysiology combined with transcriptomics elucidates synaptic restoration. LTP identifies neuron and microglia AD-relevant human-mouse co-expression modules.

Genetic and multi-omic risk assessment of Alzheimer's disease implicates core associated biological domains.

INTRODUCTION: Alzheimer's disease (AD) is the predominant dementia globally, with heterogeneous presentation and penetrance of clinical symptoms, variable presence of mixed pathologies, potential disease subtypes, and numerous associated endophenotypes. Beyond the difficulty of designing treatments that address the core pathological characteristics of the disease, therapeutic development is challenged by the uncertainty of which endophenotypic areas and specific targets implicated by those endophenotypes to prioritize for further translational research. However, publicly funded consortia driving large-scale open science efforts have produced multiple omic analyses that address both disease risk relevance and biological process involvement of genes across the genome. METHODS: Here we report the development of an informatic pipeline that draws from genetic association studies, predicted variant impact, and linkage with dementia associated phenotypes to create a genetic risk score. This is paired with a multi-omic risk score utilizing extensive sets of both transcriptomic and proteomic studies to identify system-level changes in expression associated with AD. These two elements combined constitute our target risk score that ranks AD risk genome-wide. The ranked genes are organized into endophenotypic space through the development of 19 biological domains associated with AD in the described genetics and genomics studies and accompanying literature. The biological domains are constructed from exhaustive Gene Ontology (GO) term compilations, allowing automated assignment of genes into objectively defined disease-associated biology. This rank-and-organize approach, performed genome-wide, allows the characterization of aggregations of AD risk across biological domains. RESULTS: The top AD-risk-associated biological domains are Synapse, Immune Response, Lipid Metabolism, Mitochondrial Metabolism, Structural Stabilization, and Proteostasis, with slightly lower levels of risk enrichment present within the other 13 biological domains. DISCUSSION: This provides an objective methodology to localize risk within specific biological endophenotypes and drill down into the most significantly associated sets of GO terms and annotated genes for potential therapeutic targets.

Endocrinology/Primary Care Pharmacy Collaboration vs Endocrinology Care Alone in Patients With Type 2 Diabetes and A1c >9.

Background: Type 2 diabetes (T2D) requires close collaboration between patients and their care management team, often including endocrinology. Primary care pharmacist impact on diabetes management in collaboration with endocrinology is not well established. Objective: To assess if pharmacy and endocrinology collaboration results in a greater A1c reduction in patients with T2D vs endocrinology alone. Methods: This retrospective, observational cohort study was conducted in adult outpatients with T2D and baseline A1c >9% who saw endocrinology within 1 year preceding the study period (January 1, 2021 to January 1, 2022). Patients were included if they had a follow-up A1c 6 months (±90 days) from index date and completed at least 1 endocrinology visit during the study period. Patients managed by endocrinology/primary care pharmacist collaboration (Endo/PharmD) were compared with those who received endocrinology care alone (Endo). Primary outcome was change in A1c from baseline to 6 months. Secondary outcomes included total number of completed visits and percentage of patients achieving A1c <6.5%, <7%, <8%, and <9% between groups at 6 months. Results: A total of 418 patients were included (22 Endo/PharmD, 396 Endo). The change in follow-up A1c was not significantly different between groups, -0.481% (standard error [SE] = 0.396); P = 0.6179. Endo/PharmD patients had significantly more provider visits during the study period (5.3 ± 2.3 vs 2.3 ± 1.2; P < 0.001). No significant difference was observed in odds of A1c goal attainment between groups at 6 months. Conclusion and Relevance: Endocrinology/primary care pharmacist collaboration occurred infrequently but was associated with a trend toward greater A1c reduction in patients with T2D and A1c >9%.

Risk Factors Associated with Advanced Colorectal Neoplasia in Adults Younger than Age 45.

BACKGROUND: Colorectal cancer (CRC) is rising in young adults between ages 20 to 49 years. CRC screening is endorsed for average-risk individuals beginning at ages 45 to 49 years. Targeting screening for individuals <45 years may be warranted if risk factors for advanced neoplasia can be identified. AIM: To identify factors associated with advanced colorectal neoplasia in adults aged <45 years. METHOD: Individuals ages 18 to 44 years who underwent colonoscopy at Cleveland Clinic between 2011 and 2021 with ≥1 advanced neoplasm (AN) were included. Patients with inflammatory bowel disease or inherited CRC syndromes were excluded. Demographics, comorbidities, family history of CRC, and colonoscopy indication were obtained. Patients with a normal colonoscopy constituted the control group. A multivariable logistic regression model was used to investigate the relationship between clinical variables and the presence of advanced colorectal neoplasia. RESULTS: In all, 13,006 patients were included, of which 651 (5%) patients had AN: 404 (62%) with tubular adenoma ≥10 mm, 29 (4.5%) tubular adenoma with high-grade dysplasia, 210 (32%) tubulovillous adenomas, 27 (4%) traditional serrated adenomas, 82 (13%) sessile serrated lesions ≥10 mm, 7(2%) sessile serrated lesions with dysplasia, and 29 (4.4%) patients had a CRC. Factors associated with AN were older age (means 38.5 vs. 36.6 y), history of smoking, diabetes, non-White race, higher body mass index (29.9 vs. 28.5 kg/m2), and lower vitamin D (27.6 vs. 32.2 ng/dl), all P<0.001. In the reduced multivariable model, factors associated with AN included tobacco use (OR 2.026 (current vs. never, P<0.0001), age (OR increase by 1.06 per year, P<0.0001), male gender (OR 1.476, P<0.0001), family history of CRC (OR 3.91, P<0.0001), aspirin use (1.31, P=0.035), and diabetes (OR 2.106, P 0.001). CONCLUSION: Increasing age, male gender, exposure to tobacco, family history of CRC, diabetes, and aspirin use were independently associated with advanced neoplasia in adults younger than 45. Targeted early screening to young adults with these risk factors may be justified. Large collaborative prospective studies are needed to validate our findings.

Phencyclidine Positivity on Urine Drug Screening in Patients Treated for Alcohol Withdrawal on a Dual-diagnosis Medically Assisted Withdrawal Unit.

OBJECTIVES: Little contemporary research has explored phencyclidine (PCP) use in people with alcohol use disorder. Therefore, we sought to determine the prevalence of PCP positivity on urine toxicology screening among patients admitted for alcohol withdrawal, identify correlates of PCP positivity, and investigate PCP positivity's relationship to length of stay (LOS) and risk of facility readmission. METHODS: This was a retrospective study of patients admitted to a dual-diagnosis medically assisted withdrawal unit for alcohol withdrawal from 2014 to 2019. Univariate tests and logistic regression were used to investigate potential correlates of PCP positivity on admission toxicology screening (primary outcome). Multivariable linear regression models and survival analyses analyzing LOS and risk of readmission (secondary outcomes) were also developed. RESULTS: Ninety of 3731 patients (2.4%) screened positive for PCP. There were significant associations on univariate testing between PCP positivity and age, race, homeless status, and urine toxicology positivity for amphetamines, benzodiazepines, barbiturates, cocaine, tetrahydrocannabinol, and oxycodone. On multivariate logistic regression, only tetrahydrocannabinol, barbiturates, and cocaine positivity were associated with PCP positivity. Multivariate logistic regression and survival analysis found no statistically significant associations between PCP positivity and LOS or risk of readmission. CONCLUSIONS: This study provides rare analysis of contemporary data on PCP use among patients undergoing medically assisted alcohol withdrawal. Phencyclidine positivity was uncommon, but use appears considerably higher among this patient population than the general population. There was no significant association between PCP positivity and LOS or readmission risk.

Surgical Options for the Treatment of Perianal and Anovaginal Fistulas in the Setting of Ileoanal Pouch Crohn's Disease: Experience of a Tertiary Center.

BACKGROUND: The leading cause of pouch failure following ileal pouch-anal anastomosis are peri-pouch fistulas and pelvic sepsis. OBJECTIVE: Determine the overall efficacy of current surgical therapy for the treatment of perianal and anovaginal fistulizing disease related to Crohn's disease phenotype of the pouch. DESIGN: Retrospective cohort study of a prospectively maintained, IRB-approved database. SETTINGS/PATIENTS: Ninety-one (2.3%) patients of 3058 patients with an original diagnosis of ulcerative colitis who underwent proctocolectomy with ileal pouch-anal anastomosis between 2000 and 2021 at the Cleveland Clinic and underwent postoperative surgery for Crohn's-related perianal disease. INTERVENTIONS: Two hundred thirty-one operations for perianal or anovaginal fistula(s). MAIN OUTCOME AND MEASURES: Healing rate of surgical therapy for peri-pouch fistulizing disease, impact of recurrent interventions on outcomes, and predictors of surgical failure. RESULTS: Overall mean age was 39.1 (± 11.6) years, with a BMI of 25.3 (± 6.3) kg/m2. More than half of the patients were female (n = 52, 57.1%). Sixty-three patients (69.2%) had a perianal fistula, 25 (27.5%) had an anovaginal fistula, and 3 (3.3%) patients had both. Overall success rate for healing was 59.3% (n = 54/91) at a mean follow-up of 6.4 (± 4.8) years. Seventeen (18.7%) patients underwent a concomitant diverting loop ileostomy. Among them, eight (47.0%) patients had the ileostomy closure after a mean time of 9.7 (± 2.8) months. In the multivariable logistic regression model, patients who had seton insertions in any operation were significantly less likely to heal (OR 0.11 95%, CI 0.03-0.43, p = 0.001). Overall pouch failure rate was 12.1%. LIMITATIONS: Retrospective single-center study which lacks a control arm and consistent long-term follow-up specific to a population-based dataset. CONCLUSIONS: Pouch patients who develop perianal disease are difficult to treat, sometimes requiring pouch excision. However, when medical treatment alone is not effective, a multidisciplinary approach including surgical intervention can result in complete fistula healing in more than half of the cases.

A TrkB and TrkC partial agonist restores deficits in synaptic function and promotes activity-dependent synaptic and microglial transcriptomic changes in a late-stage Alzheimer's mouse model.

Introduction: TrkB and TrkC receptor signaling promotes synaptic plasticity and interacts with pathways affected by amyloid-ß (Aß)-toxicity. Upregulating TrkB/C signaling could reduce Alzheimer's disease (AD)-related degenerative signaling, memory loss, and synaptic dysfunction. Methods: PTX-BD10-2 (BD10-2), a small molecule TrkB/C receptor partial agonist, was orally administered to aged London/Swedish-APP mutant mice (APP L/S ) and wild-type controls (WT). Effects on memory and hippocampal long-term potentiation (LTP) were assessed using electrophysiology, behavioral studies, immunoblotting, immunofluorescence staining, and RNA-sequencing. Results: Memory and LTP deficits in APP L/S mice were attenuated by treatment with BD10-2. BD10-2 prevented aberrant AKT, CaMKII, and GLUA1 phosphorylation, and enhanced activity-dependent recruitment of synaptic proteins. BD10-2 also had potentially favorable effects on LTP-dependent complement pathway and synaptic gene transcription. Conclusions: BD10-2 prevented APP L/S /Aß-associated memory and LTP deficits, reduced abnormalities in synapse-related signaling and activity-dependent transcription of synaptic genes, and bolstered transcriptional changes associated with microglial immune response.

Antemortem Health System Utilization in People Experiencing Homelessness Who Died in the Emergency Department.

People experiencing homelessness (PEH) have high rates of mortality, medical and psychiatric comorbidities, and emergency department utilization. In this study, a health system's emergency department encounters were evaluated to identify PEH who died in the emergency department. Patient demographics, medical history, prehospital and emergency department characteristics, and health care utilization patterns were collected. Descriptive statistics were calculated. We identified 48 PEH pronounced dead in the emergency department; mean age at death was 46.5. Forty-four (92%) decedents presented in cardiac arrest, 12 (25%) of which were substance use-related; 4 (8%) presented with trauma. Out of 44 patients presenting in cardiac arrest, (20.5%) had bystander cardiopulmonary resuscitation (CPR) performed before arrival of emergency medical services. In the year prior to death, 15 (32%) decedents had no documented health care utilization, while 16 (33%) had 10 or more emergency department/outpatient visits. Our study is the first to characterize PEH who died in the emergency department, analyzing the pre-hospital and in-hospital characteristics and antemortem health system utilization in this population. A sizeable proportion of deceased PEH had no health system contact in the 12 months prior to death, suggesting that those with high mortality risk may underutilize health services. Conversely, a similar proportion of decedents had extensive (more than 10) health system utilization in the year prior to death, representing possible opportunities to reduce mortality.

First in Human Subjects Testing of the UroMonitor: A Catheter-free Wireless Ambulatory Bladder Pressure Monitor.

PURPOSE: Urodynamics is the standard method of diagnosing bladder dysfunction, but involves catheters and retrograde bladder filling. With these artificial conditions, urodynamics cannot always reproduce patient complaints. We have developed a wireless, catheter-free intravesical pressure sensor, the UroMonitor, which enables catheter-free telemetric ambulatory bladder monitoring. The purpose of this study was twofold: to evaluate accuracy of UroMonitor pressure data, and assess safety and feasibility of use in humans. MATERIALS AND METHODS: Eleven adult female patients undergoing urodynamics for overactive bladder symptoms were enrolled. After baseline urodynamics, the UroMonitor was transurethrally inserted into the bladder and position was confirmed cystoscopically. A second urodynamics was then performed with the UroMonitor simultaneously transmitting bladder pressure. Following removal of urodynamics catheters, the UroMonitor transmitted bladder pressure during ambulation and voiding in private. Visual analogue pain scales (0-5) were used to assess patient discomfort. RESULTS: The UroMonitor did not significantly alter capacity, sensation, or flow during urodynamics. The UroMonitor was also easily inserted and removed in all subjects. The UroMonitor reproduced bladder pressure, capturing 98% (85/87) of voiding and nonvoiding urodynamic events. All subjects voided with only the UroMonitor in place with low post-void residual volume. Median ambulatory pain score with the UroMonitor was rated 0 (0-2). There were no post-procedural infections or changes to voiding behavior. CONCLUSIONS: The UroMonitor is the first device to enable catheter-free telemetric ambulatory bladder pressure monitoring in humans. The UroMonitor appears safe and well tolerated, does not impede lower urinary tract function, and can reliably identify bladder events compared to urodynamics.

Utility of endoscopic ultrasound for assessment of locoregional recurrence of pancreatic adenocarcinoma after surgical resection.

Background and study aims Up to 80 % of patients with pancreatic adenocarcinoma develop locoregional recurrence after primary resection. However, the detection of recurrent pancreatic ductal adenocarcinoma (RPDAC) after pancreatic surgery can be challenging because of difficulty distinguishing locoregional recurrence from normal postoperative or post-radiation changes. We sought to evaluate the utility of endoscopic ultrasound (EUS), in detecting pancreatic adenocarcinoma recurrence after surgical resection and its impact on the clinical management of patients. Patients and methods This was a retrospective study of all pancreatic cancer patients who underwent EUS post-resection at two tertiary care centers between January 2004 and June 2019. Results Sixty-seven patients were identified. Of these, 57 (85 %) were diagnosed with RPDAC, resulting in change in clinical management of 46 (72 %) patients. EUS identified masses not seen on computed tomography, magnetic resonance imaging, or positron emission tomography in seven (14 %). Conclusions EUS is useful in detecting RPDAC after pancreatic surgery and can lead to significant impact on clinical management.

Assessment of Cerebral Autoregulation Using Invasive and Noninvasive Methods of Intracranial Pressure Monitoring.

BACKGROUND: Pulse amplitude index (PAx), a descriptor of cerebrovascular reactivity, correlates the changes of the pulse amplitude of the intracranial pressure (ICP) waveform (AMP) with changes in mean arterial pressure (MAP). AMP relies on cerebrovascular compliance, which is modulated by the state of the cerebrovascular reactivity. PAx can aid in prognostication after acute brain injuries as a tool for the assessment of cerebral autoregulation and could potentially tailor individual management; however, invasive measurements are required for its calculation. Our aim was to evaluate the relationship between noninvasive PAx (nPAx) derived from a novel noninvasive device for ICP monitoring and PAx derived from gold standard invasive methods. METHODS: We retrospectively analyzed invasive ICP (external ventricular drain) and non-invasive ICP (nICP), via mechanical extensometer (Brain4Care Corp.). Invasive and non-invasive ICP waveform morphology data was collected in adult patients with brain injury with arterial blood pressure monitoring. The time series from all signals were first treated to remove movement artifacts. PAx and nPAx were calculated as the moving correlation coefficients of 10-s averages of AMP or non-invasive AMP (nAMP) and MAP. AMP/nAMP was determined by calculating the fundamental frequency amplitude of the ICP/nICP signal over a 10-s window, updated every 10-s. We then evaluated the relationship between invasive PAx and noninvasive nPAx using the methods of repeated-measures analysis to generate an estimate of the correlation coefficient and its 95% confidence interval (CI). The agreement between the two methods was assessed using the Bland-Altman test. RESULTS: Twenty-four patients were identified. The median age was 53.5 years (interquartile range 40-70), and intracranial hemorrhage (84%) was the most common etiology. Twenty-one (87.5%) patients underwent mechanical ventilation, and 60% were sedated with a median Glasgow Coma Scale score of 8 (7-15). Mean PAx was 0.0296 ± 0.331, and nPAx was 0.0171 ± 0.332. The correlation between PAx and nPAx was strong (R = 0.70, p < 0.0005, 95% CI 0.687-0.717). Bland-Altman analysis showed excellent agreement, with a bias of - 0.018 (95% CI - 0.026 to - 0.01) and a localized regression trend line that did not deviate from 0. CONCLUSIONS: PAx can be calculated by conventional and noninvasive ICP monitoring in a statistically significant evaluation with strong agreement. Further study of the applications of this clinical tool is warranted, with the goal of early therapeutic intervention to improve neurologic outcomes following acute brain injuries.

A Field-expedient Arm Care Screening Tool Can Identify Musculoskeletal Risk Factors in Baseball Players.

BACKGROUND: Preseason movement screening can identify modifiable risk factors, deterioration of function, and potential for injury in baseball players. Limited resources and time prevent high school baseball coaches from performing movement screens on their players. HYPOTHESIS: The arm care screen (ACS) will be highly sensitive to detecting musculoskeletal risk factors. STUDY DESIGN: Cross-sectional. LEVEL OF EVIDENCE: Level 3. METHODS: A total of 150 baseball players were independently scored on the ACS electronically by reviewing a video recording of each player's screening performance. Discriminability of the ACS was determined with a 2 × 2 contingency table dichotomizing musculoskeletal risk factors as present or absent based on a predetermined cutoff value and those who passed or failed the corresponding ACS subtest. RESULTS: High sensitivity was observed on the reciprocal shoulder mobility (0.89; 95% CI 0.81-0.94), 90/90 total body rotation (0.86; 95% CI 0.79-0.92), and lower body diagonal reach (0.85; 95% CI 0.78-0.91) tests of the ACS suggesting sufficient ability to identify musculoskeletal impairments and risk factors. CONCLUSION: The ACS is a simplistic screening tool that the coach can administer to discriminate between youth, high school, and college-level baseball players who possess musculoskeletal risk factors. The ACS subtests demonstrated high sensitivity for correctly identifying musculoskeletal risk factors common in baseball players and can be useful as a screening tool for baseball coaches developing arm care exercise programs. CLINICAL RELEVANCE: A field-expedient screen could provide coaches the ability to identify musculoskeletal risk factors that need to be addressed to minimize injury risk factors in a time-efficient manner.

Post-infarction ventricular septal defect: percutaneous or surgical management in the UK national registry.

AIMS: Post-infarction ventricular septal defect (PIVSD) is a mechanical complication of acute myocardial infarction (AMI) with a poor prognosis. Surgical repair is the mainstay of treatment, although percutaneous closure is increasingly undertaken. METHODS AND RESUTS: Patients treated with surgical or percutaneous repair of PIVSD (2010-2021) were identified at 16 UK centres. Case note review was undertaken. The primary outcome was long-term mortality. Patient groups were allocated based upon initial management (percutaneous or surgical). Three-hundred sixty-two patients received 416 procedures (131 percutaneous, 231 surgery). 16.1% of percutaneous patients subsequently had surgery. 7.8% of surgical patients subsequently had percutaneous treatment. Times from AMI to treatment were similar [percutaneous 9 (6-14) vs. surgical 9 (4-22) days, P = 0.18]. Surgical patients were more likely to have cardiogenic shock (62.8% vs. 51.9%, P = 0.044). Percutaneous patients were substantially older [72 (64-77) vs. 67 (61-73) years, P < 0.001] and more likely to be discussed in a heart team setting. There was no difference in long-term mortality between patients (61.1% vs. 53.7%, P = 0.17). In-hospital mortality was lower in the surgical group (55.0% vs. 44.2%, P = 0.048) with no difference in mortality after hospital discharge (P = 0.65). Cardiogenic shock [adjusted hazard ratio (aHR) 1.97 (95% confidence interval 1.37-2.84), P < 0.001), percutaneous approach [aHR 1.44 (1.01-2.05), P = 0.042], and number of vessels with coronary artery disease [aHR 1.22 (1.01-1.47), P = 0.043] were independently associated with long-term mortality. CONCLUSION: Surgical and percutaneous repair are viable options for management of PIVSD. There was no difference in post-discharge long-term mortality between patients, although in-hospital mortality was lower for surgery.

Are There Differences in the Cranial Base of Humans and Apes?

PURPOSE: Differences in skull-base angles between humans, other hominid species and apes might account for the ability of humans to develop complex speech. This study compared midline skull base angles, and angles related to insertion of skull base musculature between these species. METHODS: 126 human adult, 29 adolescent, 19 children, and 13 fetus skulls were compared to 32 ape and a subset of non-human antiquity hominid casts of skulls (13). Cranial base measurements were taken using an eMicroscribe 3d G2 digitizer. Midline and muscle insertion measurements were obtained. RESULTS: There were statistical differences in both the midline angles of the skull base (humans, 119o; apes, 130o) and in the Skull base angles related to points of muscle insertion (humans, 113o; apes, 124o), with humans exhibiting a more acute angle than the apes and other non-human hominids. There were no differences between human adults and children CONCLUSION: Acute angle differentiation of the midline skull base between humans and apes was confirmed with an alternate measurement method. Whether these angular differences are the primary reason for the lower position of the larynx in humans and the potential for more complex speech is still in debate.

Natural Analogues in pH Variability and Predictability across the Coastal Pacific Estuaries: Extrapolation of the Increased Oyster Dissolution under Increased pH Amplitude and Low Predictability Related to Ocean Acidification.

Coastal-estuarine habitats are rapidly changing due to global climate change, with impacts influenced by the variability of carbonate chemistry conditions. However, our understanding of the responses of ecologically and economically important calcifiers to pH variability and temporal variation is limited, particularly with respect to shell-building processes. We investigated the mechanisms driving biomineralogical and physiological responses in juveniles of introduced (Pacific; Crassostrea gigas) and native (Olympia; Ostrea lurida) oysters under flow-through experimental conditions over a six-week period that simulate current and future conditions: static control and low pH (8.0 and 7.7); low pH with fluctuating (24-h) amplitude (7.7 ± 0.2 and 7.7 ± 0.5); and high-frequency (12-h) fluctuating (8.0 ± 0.2) treatment. The oysters showed physiological tolerance in vital processes, including calcification, respiration, clearance, and survival. However, shell dissolution significantly increased with larger amplitudes of pH variability compared to static pH conditions, attributable to the longer cumulative exposure to lower pH conditions, with the dissolution threshold of pH 7.7 with 0.2 amplitude. Moreover, the high-frequency treatment triggered significantly greater dissolution, likely because of the oyster's inability to respond to the unpredictable frequency of variations. The experimental findings were extrapolated to provide context for conditions existing in several Pacific coastal estuaries, with time series analyses demonstrating unique signatures of pH predictability and variability in these habitats, indicating potentially benefiting effects on fitness in these habitats. These implications are crucial for evaluating the suitability of coastal habitats for aquaculture, adaptation, and carbon dioxide removal strategies.

Comparison of manual therapy techniques on ankle dorsiflexion range of motion and dynamic single leg balance in collegiate athletes.

INTRODUCTION/PURPOSE: Literature consistently identifies two key examination components when managing ankle/foot pathologies: 1) dorsiflexion range of motion (DFROM) and 2) single limb balance. Mobilizations with movement (MWM) and Instrument-Assisted Soft Tissue (IASTM) are two emerging manual therapy (MT) options in the management of ankle/foot conditions. METHODOLOGY/SAMPLE: In this observational cohort study, 147 subjects were randomized in a block fashion as follows: 1) Control, 2) IASTM, 3) MWM, and 4) Combination of both MT interventions. Descriptive statistics of the sample were conducted with integrity checks followed by comparative analysis for mean change between the variables or DFROM and YBTLQ ™ performance. RESULTS: ANOVA Welch's F indicated significant differences between the treatment conditions (Welch's F (3,75.669) = 4.533, p = .006). Games-Howell post hoc tests indicated significantly more change in DFROM in the IASTM (p = .043) and CKCMOB (p = .026) conditions when they were administered as single treatments, than in the Control Condition or when the treatments were combined. Dynamic balance, as measured by the YBT-LQ™, did not yield a significant response based on the intervention arm. DISCUSSION/CLINICAL RELEVANCE: Specifically, IASTM or closed kinetic chain (CKC) MWM MT techniques used in isolation can be considered a cost-effective intervention that can be administered by a skilled MT practitioner in a "low risk-high reward" clinical scenario with potential biomechanical and neurophysiological benefits for improving CKCDFROM.

Reported firearm access among patients admitted to a dual diagnosis medically-assisted withdrawal unit over five years.

Background: Up to one-third of firearm-related suicides were carried out by individuals who had consumed alcohol shortly before their death. Despite the critical role of firearm access screening in suicide risk assessment, few studies have examined firearm access among patients with substance use disorders. This study examines the rates of firearm access among those admitted to a co-occurring diagnosis unit over a five year period. Methods: All patients admitted to a co-occurring disorders inpatient unit from 2014 to mid-2020 were included. An analysis contrasting the differences among patients reporting firearms was performed. A multivariable logistic regression model using factors from initial admission were chosen based on clinical relevance, past firearms research, and statistical significance on bivariate analysis was used. Results: Over the study period there were 7332 admissions representing 4055 patients. Documentation of firearm access was completed in 83.6% of admissions. Firearm access was reported in 9.4% of admissions. Patients reporting firearm access were more likely to report never having suicidal ideation (p = 0.001), be married (p = <0.001), and report no past history of suicide attempts (p = <0.001). The full logistic regression model revealed that being married (OR: 2.29 and p < 0.0001) and employed (OR: 1.51 and p = 0.024) were factors associated with firearms access. Conclusions: This is one of the largest reports assessing factors associated with firearm access among those admitted to a co-occurring disorders unit. Firearm access rates in this population appear lower than rates in the general population. The roles employment and marital status play in firearm access deserve future attention.

Real-World Effectiveness and Safety of Ustekinumab in Elderly Crohn's Disease Patients.

INTRODUCTION: The efficacy and safety profile of ustekinumab (UST) in Crohn's disease (CD) is favorable; however, data in elderly patients are lacking. We aimed to assess the safety and efficacy of UST in elderly CD. METHODS: We performed a retrospective cohort study of CD patients classified as elderly (age ≥ 65 years at UST initiation) or nonelderly (<65 years) treated at a large, tertiary referral center. Outcomes assessed were clinical (measured by physician global assessment [PGA]) and steroid-free response, remission, adverse events, and postsurgical complications were compared by age category. Multivariable regression modeling and survival analysis was also performed. RESULTS: In total, 117 patients (elderly n = 39, nonelderly n = 78) were included in the study. Elderly patients had predominantly moderate disease (87.2%), while nonelderly had a higher proportion of severe disease activity (44.9%) (p = 0.001), though no differences in baseline endoscopic activity, prior biologic use, or steroid or immunomodulator use at baseline existed (p > 0.05 all). While nearly 90% patients in both groups experienced clinical response to UST, compared to nonelderly, elderly patients were less likely to achieve complete clinical remission (28.2% vs. 52.6%, p = 0.01). On regression modeling, age was not associated with clinical outcomes (p > 0.05 all). Mucosal healing was achieved in 26% elderly and 30% nonelderly patients (p = 0.74). There were no significant differences in infusion reactions (2.6% vs. 6.4%, p = 0.77), infection (5.2% vs. 7.7%, p = 0.7), or postsurgical complications (p = 0.99) by age category. CONCLUSION: UST is safe and effective in elderly CD. Although limited by sample size and retrospective design, such real-world data can inform biologic positioning in this IBD population.