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ObjectiveThe objective of this study is to compare drilling variables and torsional mechanical properties of rabbit femora after bicortical drilling with a 1.5-mm standard surgical drill bit, acrylic drill bit, and K-wire.Samples24 pairs of rabbit femora.MethodsAfter drilling under controlled axial displacement rate, each bone was biaxially loaded in compression followed by rapid external torsion to failure. Maximum axial thrust force, maximum drill torque, integral of force and displacement, change in temperature, maximum power spectral density of the torque signal, torque vibration, and torque and angle at the yield and failure points were collected. Pre- and postyield stiffness, yield and failure energies, and postyield energy were calculated.ResultsThe work required to drill through the cis- and transcortices (integral of force and displacement) was greater for the K-wire, followed by the acrylic and then standard drill bits, respectively. The K-wire demonstrated higher maximum torque than the drill bits at the ciscortex, and the force of drilling was significantly greater. The vibration data was greater with the acrylic and standard drill bits than the K-wire. There was no difference in torsional strength between drilling types.Clinical relevanceMechanical differences exist between different drill bits and K-wire and demonstrate that the K-wire is overall more damaging than the surgical drill bit.

BACKGROUND: Kidney transplant (KT) candidates with HIV face higher mortality on the waitlist compared with candidates without HIV. Because the HIV Organ Policy Equity (HOPE) Act has expanded the donor pool to allow donors with HIV (D + ), it is crucial to understand whether this has impacted transplant rates for this population. METHODS: Using a linkage between the HOPE in Action trial (NCT03500315) and Scientific Registry of Transplant Recipients, we identified 324 candidates listed for D + kidneys (HOPE) compared with 46 025 candidates not listed for D + kidneys (non-HOPE) at the same centers between April 26, 2018, and May 24, 2022. We characterized KT rate, KT type (D + , false-positive [FP; donor with false-positive HIV testing], D - [donor without HIV], living donor [LD]) and quantified the association between HOPE enrollment and KT rate using multivariable Cox regression with center-level clustering; HOPE was a time-varying exposure. RESULTS: HOPE candidates were more likely male individuals (79% versus 62%), Black (73% versus 35%), and publicly insured (71% versus 52%; P

My grandmother was 29 years old when she was admitted as a patient at the Red Cross Outpost Hospital in Paddockwood (about thirty miles north of Prince Albert, Saskatchewan, in [...]

Abstract Background Workload associated with the high frequency Colombian Paso Fino gait has not been evaluated. Objectives To determine the oxygen consumption (V̇O2), heart rate (HR), stride frequency: breathing ratio, and hematology associated with the Paso Fino gait, including whether exercise‐induced pulmonary hemorrhage (EIPH) occurs. Animals Eleven Paso Fino horses. Methods Prospective cohort study. Horses performed a standardized Paso Fino gait test across a wooden sounding board, simulating competition. V̇O2 and ventilatory parameters (tidal volume [VT]; peak inspiratory and expiratory airflows [PkV̇I, PkV̇E]; respiratory rate [RR], minute ventilation [V̇E]) were measured using a portable ergospirometry facemask. Heart rate was measured using electrocardiograms. Post‐exercise lactate, hematocrit, bicarbonate, pH, electrolytes, and biochemistry concentrations were measured. EIPH was assessed via tracheobronchoscopy. Four horses completed a secondary high‐intensity gallop to elicit peak V̇O2 for comparative purposes. Results Median [IQR] mean individual HR during the Paso Fino gait was 190 [178, 201] bpm. Relative V̇O2 measured 49.8 [48.4, 59.5] mL/(kg min; VT = 8.6 [8.0, 10.7] L; RR = 87.1 [75.4, 99.5] bpm; V̇E = 869 [740, 902] L/min; PkV̇I = 33.4 [32.7, 37.2] L/s; PkV̇E = 44.2 [40.3, 46.0] L/s). Horses took 2.8 [2.7, 2.9] strides/second and had a stride frequency: breathing ratio of 2.0 [1.8, 2.3]. Post‐exercise blood lactate concentration and hematocrit measured 2.7 mmol/L and 50% respectively. Three horses showed endoscopic evidence of Grade‐1 EIPH. The Paso Fino gait V̇O2 and HR equaled 79% V̇O2pk and 91% maximal HR, respectively, based on the high‐intensity gallop. Conclusions and Clinical Importance The Paso Fino gait represents submaximal exercise based on V̇O2

Abstract Recent research suggests that microbial molecules translocated from the intestinal lumen into the host’s internal environment may play a role in various physiological functions, including sleep. Previously, we identified that butyrate, a short-chain fatty acid produced by intestinal bacteria, and lipoteichoic acid, a cell wall component of gram-positive bacteria, induce sleep when their naturally occurring translocation is mimicked by direct delivery into the portal vein. Building upon these findings, we aimed to explore the sleep signaling potential of intraportally administered lipopolysaccharide (LPS), a primary component of gram-negative bacterial cell walls, in rats. Low dose of LPS (1 μg/kg) increased sleep duration and prolonged fever, without affecting systemic LPS levels. Interestingly, administering LPS systemically outside the portal region at a dose 20 times higher did not affect sleep, indicating a localized sensitivity within the hepatoportal region for the sleep and febrile effects of LPS. Furthermore, both the sleep- and fever-inducing effects of LPS were inhibited by indomethacin, a prostaglandin synthesis inhibitor, and replicated by intraportal administration of prostaglandin E2 or arachidonic acid, suggesting the involvement of the prostaglandin system in mediating these actions.

A 3-year-old male pit bull terrier was presented for a 4-day history of progressive tetraparesis and cervical pain. Magnetic resonance imaging confirmed an extradural mass within the left lateral vertebral canal extending from caudal C5 to mid-T2. Lumbar cerebrospinal fluid (CSF) demonstrated marked (90%) eosinophilic inflammation. A C6-7 dorsal laminectomy and C7-T2 left hemilaminectomy were done, with gross disease remaining. Histopathology revealed a large T cell lymphoma with marked eosinophilic infiltration. The dog underwent CHOP-based chemotherapy with resolution of clinical signs, with a similar course of therapy performed at recurrence 37 months after initial presentation. The dog was euthanized 39 months after presentation for multiorgan failure secondary to neutropenic sepsis and aspiration pneumonia. This represents a positive long-term response to multimodal treatment of extradural T-cell lymphoma within the vertebral canal associated with a marked CSF eosinophilia.

Yazan Gammoh,1 Priya Morjaria,2 Sandra S Block,3 Jessica Massie,4 Peter Hendicott5 1Department of Optometry Science, Al-Ahliyya Amman University, Amman, Jordan; 2International Centre for Eye Health, London School of Hygiene and Tropical Medicine, London, UK; 3Illinois College of Optometry, Chicago, Illinois, USA; 4Freelance Global Eye Health Consultant, Newcastle, New South Wales, Australia; 5Optometry and Vision Science, School of Clinical Sciences, Queensland University of Technology, Brisbane, Queensland, AustraliaCorrespondence: Yazan Gammoh, Department of Optometry Science, Al-Ahliyya Amman University, P.O.Box 121, Amman, 19328, Jordan, Email y.gammoh@ammanu.edu.joPurpose: To provide information on the demographics of optometrists and regulation of the optometry profession in countries who were members of the World Council of Optometry (WCO) during the period 2022– 2023.Methods: A non-random, purposive sampling and a key informant strategy was employed to conduct a survey-based cross-sectional study on the professional landscape and distribution of optometrists; educational landscape; legislative aspects of the profession; and the scope of optometry practice in countries who were members of WCO during the period 2022– 2023. Key informants were identified by WCO country members’ leadership.Results: In the 39 countries surveyed, one optometrist serves 23,200 persons on average. Only 46.2% of the countries met the internationally suggested 1:10,000 optometrist-to-population ratio. The average male-to-female ratio was 45% males/55% females, with a division of average age as follows: under 45 years of age 46% as compared to above 45 years of age 54%. It was reported that optometry is not regulated in France, Portugal, India, Kenya and Cameron. Thirteen countries (33%) do not require a Bachelor’s degree as a minimum to practice optometry. Use of diagnostic drugs is prohibited in 20% of the countries, with 25% of the countries limiting the use of therapeutic pharmaceutical agents.Conclusion: Many countries where optometry is recognized struggle to have an adequate number of optometrists; this hinders access to eye care. This is compounded by unregulated minimum levels of education for entry-level optometric practitioners. In addition, several countries limit or prohibit many optometric procedures that restrict the ability of optometrists to provide eye care and vision health services at the primary care level.Keywords: eye care, scope of practice, optometrist, global distribution, legislation

Abstract Background Swimming has been used empirically for rehabilitation and conditioning of horses. However, due to challenges imposed by recording physiological parameters in water, the intensity of free swimming effort is unknown. Objectives Measure the physiological workload associated with untethered swimming in horses. Five fit Arabian endurance horses were assessed while swimming in a 100 m-long indoor pool. Horses were equipped with a modified ergospirometry facemask to measure oxygen consumption (V̇O2) and ventilatory parameters (inspired/expired volumes, VI, VE; peak inspiratory/expiratory flows, PkVI, PkVE; respiratory frequency, Rf; minute ventilation, VE; inspiratory/expiratory durations and ratios, tI, tE, tI/ttot, tE/ttot); and an underwater electrocardiogram that recorded heart rate (HR). Postexercise venous blood lactate and ammonia concentrations were measured. Data are reported as median (interquartile ranges). Results Horses showed bradypnea (12 breaths/min (10–16)) for the first 30 s of swimming. V̇O2 during swimming was 43.2 ml/(kg.min) (36.0–56.6). Ventilatory parameters were: VI = 16.7 L (15.3–21.8), VE = 14.7 L (12.4–18.9), PkVI = 47.8 L/s (45.8–56.5), PkVE = 55.8 L/s (38.3–72.5), Rf = 31.4 breaths/min (20.0–33.8), VE = 522.9 L/min (414.7–580.0), tI = 0.5 s (0.5–0.6), tE = 1.2 s (1.1–1.6), tI/ttot = 0.3 (0.2–0.4), tE/ttot = 0.7 (0.6–0.8). Expiratory flow tracings showed marked oscillations that coincided with a vibrating expiratory sound. HR was 178.0 bpm (148.5–182.0), lactate = 1.5 mmol/L (1.0–1.9) and ammonia = 41.0 µmol/L (36.5–43.5). Conclusions Free (untethered) swimming represents a submaximal, primarily aerobic exercise in horses. The breathing pattern during swimming is unique, with a relatively longer apneic period at the beginning of the exercise and an inspiratory time less than half that of expiration.

BACKGROUND: Living kidney donation is possible for people living with HIV (PLWH) in the United States within research studies under the HIV Organ Policy Equity (HOPE) Act. There are concerns that donor nephrectomy may have an increased risk of end-stage renal disease (ESRD) in PLWH due to HIV-associated kidney disease and antiretroviral therapy (ART) nephrotoxicity. Here we report the first 3 cases of living kidney donors with HIV under the HOPE Act in the United States. METHODS: Within the HOPE in Action Multicenter Consortium, we conducted a prospective study of living kidney donors with HIV. Pre-donation, we estimated the 9-year cumulative incidence of ESRD, performed genetic testing of apolipoprotein L1 (APOL1), excluding individuals with high-risk variants, and performed pre-donation kidney biopsies (HOPE Act requirement). The primary endpoint was ≥grade 3 nephrectomy-related adverse events (AEs) in year one. Post-donation, we monitored glomerular filtration rate (measured by iohexol/Tc-99m DTPA [mGFR] or estimated with serum creatinine [eGFR]), HIV RNA, CD4 count, and ART. FINDINGS: There were three donors with two-four years of follow-up: a 35 year-old female, a 52 year-old male, and a 47 year-old male. Pre-donation 9-year estimated cumulative incidence of ESRD was 3.01, 8.01, and 7.76 per 10,000 persons, respectively. In two donors with APOL1 testing, no high-risk variants were detected. Biopsies from all three donors showed no kidney disease. Post-donation, two donors developed nephrectomy-related ≥grade 3 AEs: a medically-managed ileus and a laparoscopically-repaired incisional hernia. GFR declined from 103 to 84 mL/min/1.73 m2 at four years (mGFR) in donor 1, from 77 to 52 mL/min/1.73 m2 at three years (eGFR) in donor 2, and from 65 to 39 mL/min/1.73 m2 at two years (eGFR) in donor 3. HIV RNA remained

Pseudohyponatremia remains a problem for clinical laboratories. In this study, we analyzed the mechanisms, diagnosis, clinical consequences, and conditions associated with pseudohyponatremia, and future developments for its elimination. The two methods involved assess the serum sodium concentration ([Na]S) using sodium ion-specific electrodes: (a) a direct ion-specific electrode (ISE), and (b) an indirect ISE. A direct ISE does not require dilution of a sample prior to its measurement, whereas an indirect ISE needs pre-measurement sample dilution. [Na]S measurements using an indirect ISE are influenced by abnormal concentrations of serum proteins or lipids. Pseudohyponatremia occurs when the [Na]S is measured with an indirect ISE and the serum solid content concentrations are elevated, resulting in reciprocal depressions in serum water and [Na]S values. Pseudonormonatremia or pseudohypernatremia are encountered in hypoproteinemic patients who have a decreased plasma solids content. Three mechanisms are responsible for pseudohyponatremia: (a) a reduction in the [Na]S due to lower serum water and sodium concentrations, the electrolyte exclusion effect; (b) an increase in the measured sample's water concentration post-dilution to a greater extent when compared to normal serum, lowering the [Na] in this sample; (c) when serum hyperviscosity reduces serum delivery to the device that apportions serum and diluent. Patients with pseudohyponatremia and a normal [Na]S do not develop water movement across cell membranes and clinical manifestations of hypotonic hyponatremia. Pseudohyponatremia does not require treatment to address the [Na]S, making any inadvertent correction treatment potentially detrimental.

Environmental, cultural, and social issues are becoming increasingly complex, and the educational context is no exception to this trend. The relevance of teachers' creativity in examining situations from different angles, in imagining new approaches, in adapting to the varied needs of students, and in training them so that they too can grasp the teeming complexity seems obvious. However, creativity sometimes seems to be taken for granted among teachers and educational programs leave a gap around this theme. Since the scientific literature tends to show that teachers' creativity is still little explored in educational contexts, this doctoral research studies its manifestations within a group of teachers enrolled in a professional master's program in preschool and elementary education (Université de Sherbrooke, Canada). Within the framework of this program, each one elaborates a professional development project over a three-year period. Using a variety of authentic data sources (observations in natural occurring situations, reflective writing by participants, and semi-structured interviews), their creative process is documented and analyzed. This multiple-case study (n = 9) that draws on the concept of creativity as related to that of professional coherence reveals that the pursuit of greater professional coherence not only enables the implementation of creative skills to foster teachers' professional development, but also elicits beautiful risk-taking.

Objective Individuals who work on health data systems and services are uniquely positioned to understand the risks of health data collection and use. We designed and conducted a survey assessing the perceptions of those who work with health data around health data consent, sharing, and privacy practices in healthcare and clinical research. Methods A 43-item online survey was distributed via a market research firm to individuals (18+) who work with health data in the United States from March to April 2023. Descriptive statistics were calculated for all variables. Associations with demographic variables were assessed using Pearson's X 2 tests and ordinal logistic regression. Results Most of our respondents (61.7%) reported that they would trust people to use their health data across various sectors, but more respondents trusted those working in academic medical research (86.5%) and healthcare offices (89.9%) compared to those working in industry (68.2%). Despite this reported trust, a strong majority believed that individuals should have complete control over their health data (97.3%), specific consent should be obtained for each use of their health data (92.0%), and that there should be higher standards of consent and privacy for health records data than other types of data (93.7%). Conclusions Based on our findings, we might infer that people who work with health data generally trust institutions across sectors to protect their health data. However, many would prefer to have complete control over who has access to their health data and how it is used. These insights should be explored further through qualitative studies.

Abstract This article seeks to understand why deliberative civic engagement is chosen as a method of engagement by policymakers, using two jurisdictions as exploratory cases: the Nova Scotia Health Authority's [...]

Abstract Background Despite the high prevalence of neuropathic pain, treating this neurological disease remains challenging, given the limited efficacy and numerous side effects associated with current therapies. The complexity in patient management is largely attributed to an incomplete understanding of the underlying pathological mechanisms. Central sensitization, that refers to the adaptation of the central nervous system to persistent inflammation and heightened excitatory transmission within pain pathways, stands as a significant contributor to persistent pain. Considering the role of the cystine/glutamate exchanger (also designated as system xc −) in modulating glutamate transmission and in supporting neuroinflammatory responses, we investigated the contribution of this exchanger in the development of neuropathic pain. Methods We examined the implication of system xc − by evaluating changes in the expression/activity of this exchanger in the dorsal spinal cord of mice after unilateral partial sciatic nerve ligation. In this surgical model of neuropathic pain, we also examined the consequence of the genetic suppression of system xc − (using mice lacking the system xc − specific subunit xCT) or its pharmacological manipulation (using the pharmacological inhibitor sulfasalazine) on the pain-associated behavioral responses. Finally, we assessed the glial activation and the inflammatory response in the spinal cord by measuring mRNA and protein levels of GFAP and selected M1 and M2 microglial markers. Results The sciatic nerve lesion was found to upregulate system xc − at the spinal level. The genetic deletion of xCT attenuated both the amplitude and the duration of the pain sensitization after nerve surgery, as evidenced by reduced responses to mechanical and thermal stimuli, and this was accompanied by reduced glial activation. Consistently, pharmacological inhibition of system xc − had an analgesic effect in lesioned mice. Conclusion Together, these observations provide evidence for a role of system xc − in the biochemical processes underlying central sensitization. We propose that the reduced hypersensitivity observed in the transgenic mice lacking xCT or in sulfasalazine-treated mice is mediated by a reduced gliosis in the lumbar spinal cord and/or a shift in microglial M1/M2 polarization towards an anti-inflammatory phenotype in the absence of system xc −. These findings suggest that drugs targeting system xc − could contribute to prevent or reduce neuropathic pain.

Hemp (Cannabis sativa) is a new crop for Oregon and Washington. These states are also home to 90% of the country's hop (Humulus lupulus) production. Powdery mildew is a common disease that affects both hemp and hop. There are at least two species of powdery mildew fungi that may occur on hemp, including Golovinomyces ambrosiae and Podosphaera macularis, with the latter also infecting hop. Surveys were conducted throughout Oregon and Washington in 2021 and 2022 to determine the incidence and identity of powdery mildew fungi on hemp. Seventy-four fields were evaluated at three time points. In Oregon, powdery mildew was not detected in either year in the early season but was detected in 4.6 to 6.5% of fields during mid-season and 36.8 to 41.4% of fields during late-season evaluations. Powdery mildew was not detected in Washington in any survey time point in either year. We collected 204 powdery mildew samples from surveyed fields. Both P. macularis and G. ambrosiae were detected on hemp, based on diagnostic PCR assays and sequencing, comprising approximately 17 and 96% of assayed survey samples, respectively. All P. macularis samples that amplified were mating type MAT1-1, consistent with the population occurring on hop in the region. Thirty-nine convenience samples were collected outside of surveyed fields and included the first detections of both G. ambrosiae and P. macularis on hemp in Washington. The presence of P. macularis on hemp has possible ramifications for hop producers in the region, including disruption of established management systems and introduction of novel isolates. [Figure: see text] The author(s) have dedicated the work to the public domain under the Creative Commons CC0 “No Rights Reserved” license by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law, 2024.

Abstract Background Comparatively little is known regarding the initial cardiorespiratory response of young racehorses to training. The objectives were to compare physiological parameters before and after introductory training and determine whether young Thoroughbreds show endoscopic signs of exercise-induced pulmonary hemorrhage (EIPH). Ten Thoroughbreds (20–23 months) underwent 12-weeks of introductory training, including weekly speed sessions. Two 600 m high-speed exercise tests (HSET) were performed following weeks 4 and 12 while wearing a validated ergospirometry facemask. Peak oxygen consumption (V̇O2pk) and ventilatory parameters (tidal volume, VT; peak inspiratory and expiratory flow, PkV̇I, PkV̇E; respiratory frequency, Rf; minute ventilation, V̇E) were measured. The ventilatory equivalent of oxygen (V̇E/V̇O2) and the aerobic and anaerobic contributions to energy production were calculated. Maximal heart rate (HRmax) and HR at maximal speed (HRVmax) were determined. Post-exercise hematocrit, plasma ammonia and blood lactate were measured. Evidence of EIPH was investigated via tracheobronchoscopy post-exercise. Results were compared (paired t-test, P

Decreased postdonation eGFR is associated with a higher risk of ESRD after living kidney donation, even when accounting for predonation characteristics. The Toulouse-Rangueil model (TRM) estimates 12 month postdonation eGFR (eGFR12) to inform counseling of candidates for living donation. The TRM was validated in several single-center European cohorts but has not been validated in US donors. We assessed the TRM in living kidney donors in the US using SRTR data 1/2000-6/2021. We compared the 2021 CKD-EPI equation eGFR12 observed estimates to the TRM eGFR12 predictions. Median (IQR) bias was -3.4 (-9.3, 3.4) mL/min/1.73 m2. Bias was higher for males vs. females (bias [IQR] -4.4 [-9.9, 1.8] vs. -2.9 [-8.8, 4.1]) and younger (31-40) vs. older donors (>50) (bias -4.9 [-10.6, 3.0] vs. -2.1 [-7.5, 4.0]). Bias was also larger for Black vs. White donors (bias (-6.7 [-12.1, -0.3], p < 0.001) vs. (-3.4 [-9.1, 3.1], p < 0.001)). Overall correlation was 0.71. In a sensitivity analysis using the 2009 CKD-EPI equation, results were generally consistent with exception to a higher overall bias (bias -4.2 [-9.8, 2.4]). The TRM overestimates postdonation renal function among US donors. Overestimation was greatest for those at higher risk for postdonation ESRD including male, Black, and younger donors. A new equation is needed to estimate postdonation renal function.

Summary: Prostate cancer screening using prostate-specific antigen (PSA) has been shown to reduce mortality but with substantial overdiagnosis, leading to unnecessary biopsies. The identification of a highly specific biomarker using liquid biopsies, represents an unmet need in the diagnostic pathway for prostate cancer. In this study, we employed a method that enriches for methylated cell-free DNA fragments coupled with a machine learning algorithm which enabled the detection of metastatic and localized cancers with AUCs of 0.96 and 0.74, respectively. The model also detected 51.8% (14/27) of localized and 88.7% (79/89) of patients with metastatic cancer in an external dataset. Furthermore, we show that the differentially methylated regions reflect epigenetic and transcriptomic changes at the tissue level. Notably, these regions are significantly enriched for biologically relevant pathways associated with the regulation of cellular proliferation and TGF-beta signaling. This demonstrates the potential of circulating tumor DNA methylation for prostate cancer detection and prognostication.

BackgroundLittle is known about left ventricular (LV) sequences of contraction and electrical activation in hypertrophic cardiomyopathy (HCM). A better understanding of the underlying relation between mechanical and electrical activation may allow the identification of predictive response criteria to right ventricular DDD pacing in obstructive patients.ObjectiveTo describe LV mechanical and electrical activation sequences in HCM patients compared to controls.Materials and methodsWe prospectively studied, in 40 HCM patients (20 obstructive and 20 non-obstructive) and 20 healthy controls: (1) mechanical activation using echocardiography at rest and cardiac magnetic resonance imaging, (2) electrical activation using 3-dimensional electrocardiographic mapping (ECM).ResultsIn echocardiography, healthy controls had a physiological apex-to-base delay (ABD) during contraction (23.8 ± 16.2 ms). Among the 40 HCM patients, 18 HCM patients presented a loss of this ABD (

Background. The HIV Organ Policy Equity Act legalizes organ procurement from donors with HIV (HIV D+). A prior survey of Organ Procurement Organizations (OPOs) estimated >2000 HIV D+ referrals/year; however, only 30–35 HIV D+/year have had organs procured. Given this gap, we sought to understand HIV D+ referrals and procurements in practice. Methods. We prospectively collected data on all OPO-reported HIV D+ referrals, including reasons for nonprocurement. We evaluated trends and compared HIV D+ characteristics by procurement status using regression, chi-squared tests, and Wilcoxon rank-sum tests. Results. From December 23, 2015 to May 31, 2021, there were 710 HIV D+ referrals from 49 OPOs, of which 171 (24%) had organs procured. HIV D+ referrals increased from 7 to 15 per month (P

Subclavian steal syndrome results from subclavian artery stenosis that results in retrograde blood flow through the ipsilateral vertebral artery. Rarely, this retrograde flow can affect the vertebrobasilar junction and cause vertebrobasilar insufficiency, ischemia, and even aneurysm formation. We describe a unique presentation of a vertebrobasilar aneurysm presenting with subarachnoid hemorrhage in the setting of subclavian steal syndrome. The subclavian stenosis was endovascularly managed, with complete resolution of both retrograde flow and the dissection itself. Reestablishment of native flow mechanics in the subclavian artery may treat aneurysms at the vertebrobasilar junction, potentially eliminating the need for further interventions.

UNLABELLED: ABO type B and O kidney transplant candidates have increased difficulty identifying a compatible donor for living donor kidney transplantation (LDKT) and are harder to match in kidney paired donation registries. A2-incompatible (A2i) LDKT increases access to LDKT for these patients. To better inform living donor selection, we evaluated the association between A2i LDKT and patient and graft survival. METHODS: We used weighted Cox regression to compare mortality, death-censored graft failure, and all-cause graft loss in A2i versus ABO-compatible (ABOc) recipients. RESULTS: Using Scientific Registry of Transplant Recipients data 2000-2019, we identified 345 A2i LDKT recipients. Mortality was comparable among A2i and ABOc recipients; weighted 1-/5-/10-y mortality was 0.9%/6.5%/24.2%, respectively, among A2i LDKT recipients versus 1.4%/7.7%/22.2%, respectively, among ABOc LDKT recipients (weighted hazard ratio [wHR], 0.811.041.33; P = 0.8). However, A2i recipients faced higher risk of death-censored graft failure; weighted 1-/5-/10-y graft failure was 5.7%/11.6%/22.4% for A2i versus 1.7%/7.5%/17.2% for ABOc recipients (wHR in year 1 = 2.243.565.66; through year 5 = 1.251.782.53; through year 10 = 1.151.552.07). By comparison, 1-/5-/10-y wHRs for A1-incompatible recipients were 0.631.966.08/0.390.942.27/0.390.831.74. CONCLUSIONS: A2i LDKT is generally safe, but A2i donor/recipient pairs should be counseled about the increased risk of graft failure and be monitored as closely as their A1-incompatible counterparts posttransplant.

Background: In patients with anterior ST-elevation myocardial infarction (STEMI) and new-onset antero-apical wall motion abnormalities (WMAs), whether the rate of prophylaxis against left ventricular thrombus and outcomes differ between men and women is unknown. Methods: A multicentre retrospective cohort study of patients with STEMI and new-onset antero-apical WMAs treated with primary percutaneous coronary intervention was conducted. Patients with an established indication of oral anticoagulation (OAC) were excluded. The rates of triple therapy (double antiplatelet therapy + OAC) at discharge were compared for women vs men. The rates of net adverse clinical events, a composite of mortality, myocardial infarction, stroke or transient ischemic attack, systemic thromboembolism or Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding at 6 months were compared across sex using a multivariate logistic regression model. Results: A total of 1664 patients were included in the primary analysis, of whom 402 (24.2%) were women and 1262 (75.8%) were men. A total of 138 women (34.3%) and 489 men (38.7%) received a triple therapy prescription at discharge (P = 0.11). At 6 months, 33 women (8.2%) and 96 men (7.6%) experienced a net adverse clinical event (adjusted odds ratio 0.82; 95% confidence interval 0.49-1.37). No difference occurred in the risk of bleeding events and ischemic events between men and women, when these were analyzed separately. Conclusions: The rates of OAC prescription for left ventricular thrombus prophylaxis and clinical outcomes at 6 months were similar in women and men following anterior STEMI with new-onset antero-apical WMAs. Résumé: Contexte: On ignore si le taux de prophylaxie contre le thrombus ventriculaire gauche et les résultats thérapeutiques diffèrent entre les hommes et les femmes qui ont subi un infarctus du myocarde avec élévation du segment ST (STEMI) antérieur et ont des anomalies du mouvement pariétal (AMP) antéroapical d’apparition récente. Méthodes: Nous avons mené une étude de cohorte rétrospective multicentrique auprès de patients qui ont subi un STEMI et ont des AMP d’apparition récente traitées par une intervention coronarienne percutanée primaire. Nous avons exclu les patients chez lesquels il existait une indication établie à l’anticoagulation orale (ACO). Nous avons comparé les taux de trithérapie (bithérapie antiplaquettaire + ACO) à la sortie de l’hôpital entre les femmes et les hommes. Nous avons comparé les taux d’événements indésirables cliniques nets, le critère composite de mortalité, d’infarctus du myocarde, d’accident vasculaire cérébral ou d’accident ischémique transitoire, la thromboembolie systémique ou l’hémorragie de type 3 ou 5 selon le Bleeding Academic Research Consortium (BARC) après 6 mois entre les sexes au moyen du modèle de régression logistique multivariée. Résultats: Au sein des 1 664 patients de l’analyse principale, 402 (24,2 %) étaient des femmes et 1262 (75,8 %) étaient des hommes. Un total de 138 femmes (34,3 %) et de 489 hommes (38,7 %) ont reçu une ordonnance de trithérapie à la sortie de l’hôpital (P = 0,11). Après 6 mois, 33 femmes (8,2 %) et 96 hommes (7,6 %) ont subi un événement indésirable net (rapport de cotes ajusté 0,82 ; intervalle de confiance à 95 % 0,49-1,37). Aucune différence n’a été notée dans le risque d’événements hémorragiques et d’événements ischémiques entre les hommes et les femmes lorsque ces événements étaient analysés séparément. Conclusions: Les taux d’ordonnances d’ACO en prophylaxie du thrombus ventriculaire gauche et les résultats cliniques après 6 mois étaient similaires entre les femmes et les hommes à la suite du STEMI antérieur et des AMP antéroapicale d’apparition récente.

Abstract Acute Myeloid Leukemia (AML) is a heterogeneous disease with limited treatment options and a high demand for novel targeted therapies. Since myeloid-related protein S100A9 is abundantly expressed in AML, we aimed to unravel the therapeutic impact and underlying mechanisms of targeting both intracellular and extracellular S100A9 protein in AML cell lines and primary patient samples. S100A9 silencing in AML cell lines resulted in increased apoptosis and reduced AML cell viability and proliferation. These therapeutic effects were associated with a decrease in mTOR and endoplasmic reticulum stress signaling. Comparable results on AML cell proliferation and mTOR signaling could be observed using the clinically available S100A9 inhibitor tasquinimod. Interestingly, while siRNA-mediated targeting of S100A9 affected both extracellular acidification and mitochondrial metabolism, tasquinimod only affected the mitochondrial function of AML cells. Finally, we found that S100A9-targeting approaches could significantly increase venetoclax sensitivity in AML cells, which was associated with a downregulation of BCL-2 and c-MYC in the combination group compared to single agent therapy. This study identifies S100A9 as a novel molecular target to treat AML and supports the therapeutic evaluation of tasquinimod in venetoclax-based regimens for AML patients.