Enhancing Liver Transplant Outcomes through Liver Precooling to Mitigate Inflammatory Response and Protect Mitochondrial Function.

Transplanted organs experience several episodes of ischemia and ischemia-reperfusion. The graft injury resulting from ischemia-reperfusion (IRI) remains a significant obstacle to the successful survival of transplanted grafts. Temperature significantly influences cellular metabolic rates because biochemical reactions are highly sensitive to temperature changes. Consequently, lowering the temperature could reduce the degradative reactions triggered by ischemia. In mitigating IRI in liver grafts, the potential protective effect of localized hypothermia on the liver prior to blood flow obstruction has yet to be explored. In this study, we applied local hypothermia to mouse donor livers for a specific duration before stopping blood flow to liver lobes, a procedure called "liver precooling". Mouse donor liver temperature in control groups was controlled at 37 °C. Subsequently, the liver donors were preserved in cold University of Wisconsin solution for various durations followed by orthotopic liver transplantation. Liver graft injury, function and inflammation were assessed at 1 and 2 days post-transplantation. Liver precooling exhibited a significant improvement in graft function, revealing more than a 47% decrease in plasma aspartate transaminase (AST) and alanine aminotransferase (ALT) levels, coupled with a remarkable reduction of approximately 50% in liver graft histological damage compared to the control group. The protective effects of liver precooling were associated with the preservation of mitochondrial function, a substantial reduction in hepatocyte cell death, and a significantly attenuated inflammatory response. Taken together, reducing the cellular metabolism and enzymatic activity to a minimum level before ischemia protects against IRI during transplantation.

Measuring practice preference variation for quality improvement in neonatal respiratory care.

OBJECTIVES: The authors sought to measure and compare practice preference variation in neonatal respiratory care within and between neonatal intensive care units (NICUs) using the Neonatology Survey of Interdisciplinary Groups in Healthcare Tool (NSIGHT). STUDY DESIGN: Eleven NICUs completed the NSIGHT between 2019 and 2021. Net preference was measured by mean response; agreement was ranked by standard distribution of response values. Heat maps showed comparisons between NICUs and disciplines. RESULTS: NICUs and individuals agreed most often on use of pressure support with mandatory ventilation and on use of non-invasive positive pressure ventilation for apnea. High preference variation surrounded decisions for invasive ventilation versus continuous positive airway pressure for extremely low birth weight infants. Preference difference was most frequent between neonatologists and nurses. CONCLUSIONS: Patterns of practice preference variation in neonatal respiratory care are specific to clinical scenario. Measuring preference variation may inform psychology of change and strengthen quality improvement efforts.

Hemodynamic Renal Reserve Response in Conscious Normotensive and Hypertensive Mice.

INTRODUCTION: Renal function may be compromised following recovery from kidney insults. Renal functional reserve (RFR) is a measure of the difference between the kidney's maximum capacity and its baseline function, which helps identify any areas of the kidney with compromised function. Usually, RFR is evaluated using acute volume expansion (AVE), but this is typically done in anesthetized animals, which may not accurately represent the kidney's complete functional capacity. In this study, we have introduced a novel method that enables AVE to be conducted in conscious mice. METHODS: We have implemented this innovative approach in two animal models representing either intact or impaired renal function, specifically utilizing a lower nephron hypertensive model. Mice were implanted with radio-transmitters for mean artery blood pressure (MAP) monitoring during the experiment. After recovery, half of the mice were induced hypertension by right kidney nephrectomy combined with the ligation of the upper branch of the left kidney. For the AVE, a volume equivalent to 5% of the mouse's body weight was administered via intravenous (IV) or intraperitoneal bolus injection. Subsequently, the mice were individually housed in cages covered with plastic wrap. Urine was collected every hour for a total of 3 h for the measurement of urine and sodium excretion. RESULTS: The MAPs for all normotensive mice were consistent throughout the AVE, but it increased 5-16 mm Hg in the hypertensive mice upon AVE. Remarkably, conscious mice exhibited a significantly stronger response to IV-administered AVE when compared to anesthetized mice. This response was evident in the increase in urinary flow, which was approximately 170% and 145% higher in conscious normotensive and hypertensive mice, respectively, compared to their respective baselines. In contrast, anesthetized normotensive and hypertensive mice showed only around a 130% and 100% increase in urinary flow, respectively. Additionally, upon AVE, conscious normotensive mice excreted approximately 47% more sodium than conscious hypertensive mice. In contrast, anesthetized normotensive mice excreted only about 30% more sodium than their anesthetized hypertensive counterparts. CONCLUSION: Performing a kidney stress test with a significant solution load in conscious mice seems to be a superior method for evaluating RFR compared to conducting the test under anesthesia. Assessing kidney clearance while the mice are conscious has the potential to enhance the precision of diagnosing and predicting both acute and chronic kidney diseases.

Consensus Paper: Cerebellum and Ageing.

Given the key roles of the cerebellum in motor, cognitive, and affective operations and given the decline of brain functions with aging, cerebellar circuitry is attracting the attention of the scientific community. The cerebellum plays a key role in timing aspects of both motor and cognitive operations, including for complex tasks such as spatial navigation. Anatomically, the cerebellum is connected with the basal ganglia via disynaptic loops, and it receives inputs from nearly every region in the cerebral cortex. The current leading hypothesis is that the cerebellum builds internal models and facilitates automatic behaviors through multiple interactions with the cerebral cortex, basal ganglia and spinal cord. The cerebellum undergoes structural and functional changes with aging, being involved in mobility frailty and related cognitive impairment as observed in the physio-cognitive decline syndrome (PCDS) affecting older, functionally-preserved adults who show slowness and/or weakness. Reductions in cerebellar volume accompany aging and are at least correlated with cognitive decline. There is a strongly negative correlation between cerebellar volume and age in cross-sectional studies, often mirrored by a reduced performance in motor tasks. Still, predictive motor timing scores remain stable over various age groups despite marked cerebellar atrophy. The cerebello-frontal network could play a significant role in processing speed and impaired cerebellar function due to aging might be compensated by increasing frontal activity to optimize processing speed in the elderly. For cognitive operations, decreased functional connectivity of the default mode network (DMN) is correlated with lower performances. Neuroimaging studies highlight that the cerebellum might be involved in the cognitive decline occurring in Alzheimer's disease (AD), independently of contributions of the cerebral cortex. Grey matter volume loss in AD is distinct from that seen in normal aging, occurring initially in cerebellar posterior lobe regions, and is associated with neuronal, synaptic and beta-amyloid neuropathology. Regarding depression, structural imaging studies have identified a relationship between depressive symptoms and cerebellar gray matter volume. In particular, major depressive disorder (MDD) and higher depressive symptom burden are associated with smaller gray matter volumes in the total cerebellum as well as the posterior cerebellum, vermis, and posterior Crus I. From the genetic/epigenetic standpoint, prominent DNA methylation changes in the cerebellum with aging are both in the form of hypo- and hyper-methylation, and the presumably increased/decreased expression of certain genes might impact on motor coordination. Training influences motor skills and lifelong practice might contribute to structural maintenance of the cerebellum in old age, reducing loss of grey matter volume and therefore contributing to the maintenance of cerebellar reserve. Non-invasive cerebellar stimulation techniques are increasingly being applied to enhance cerebellar functions related to motor, cognitive, and affective operations. They might enhance cerebellar reserve in the elderly. In conclusion, macroscopic and microscopic changes occur in the cerebellum during the lifespan, with changes in structural and functional connectivity with both the cerebral cortex and basal ganglia. With the aging of the population and the impact of aging on quality of life, the panel of experts considers that there is a huge need to clarify how the effects of aging on the cerebellar circuitry modify specific motor, cognitive, and affective operations both in normal subjects and in brain disorders such as AD or MDD, with the goal of preventing symptoms or improving the motor, cognitive, and affective symptoms.

A Tensionable and Retensionable Knotless Anchor Repair Construct for Compression After Reduction of Tibial Avulsion Fracture of Anterior Cruciate Ligament.

Tibial avulsion fractures comprise a subset of anterior cruciate ligament injuries. Primary fixation methods have traditionally used either screw or suture fixation. New anchor and suture technologies have led to the development of tensionable and retensionable techniques. These newer techniques allow for not only anatomic reduction but also further compression after reduction. The purpose of this technical note is to introduce a tensionable and retensionable construct that uses knotless anchor fixation to produce compression after anatomic reduction of a tibial avulsion fracture.

Tocilizumab Treatment in COVID-19 Patients: Comparing Cutaneous Disease and Adverse Drug Effects.

Actemra (tocilizumab) received emergency use authorization for the treatment of coronavirus disease 2019 (COVID-19) in June 2021. Literature has linked numerous cutaneous adverse effects to tocilizumab. In this current survey, investigators reviewed and compared these adverse effects to the common cutaneous manifestations of COVID-19. While similarities in patient presentation exist, important distinctions are made to aid dermatologists in their clinical diagnosis.  J Drugs Dermatol. 2023;22(12):e42-e43.     doi:10.36849/JDD.6532e.

Trends in Patient-Reported Outcomes Measurement Information System (PROMIS) Utilization in Orthopedic Sports Medicine: A Scoping Review.

Background: The Patient-Reported Outcomes Measurement Information System (PROMIS) developed by the National Institutes of Health provides a standardized method for collecting outcomes data from sports medicine patient populations. Methods: The objective of this scoping review is to report on PROMIS utilization in orthopedic sports medicine research and practice. We searched PubMed, ScienceDirect, and Cochrane Library using keywords and database-specific subject headings to identify studies that reported PROMIS utilization. Inclusion criteria were the use or mention of PROMIS in any population of patients commonly treated by orthopedic sports medicine physicians. Results: Following a screening process, we included 67 studies published from 2019 through 2022 in this review. A near-equal distribution of studies was published per year during this period. Twenty-four domains were assessed across the studies. Among studies with adult populations, the Pain Interference (45 studies, 67%) and Physical Function (37 studies, 55%) domains were the 2 most reported by researchers. Upper Extremity (4 studies, 6%) and Mobility (3 studies, 4%) were the 2 most used domains in studies involving pediatric populations. Conclusion: Our results demonstrate consistent utilization of PROMIS domains in the field of sports medicine. Researchers commonly used PROMIS with other legacy measures, comparing the scores to one another to assess responsiveness and validity. This review provides evidence that PROMIS domains are being used to collect data on a variety of factors related to sports medicine patient outcomes that may help physicians better understand the complexities of the recovery and rehabilitation process.

Implementation of a dedicated cascade testing clinic for patients at risk for hereditary cancer syndromes.

Cascade testing, the site-specific genetic testing of relatives within families with an inherited condition, is underutilized. Long wait times for appointments in specialty genetics clinics are a known barrier to genetic testing access. In our cancer genetics, New Patient Clinic (NPC), the long wait time for an appointment (on average 5 months for routine referrals), was identified by both providers and patients as a barrier to uptake of cascade testing. Timely testing of at-risk relatives is essential to maximize the benefits of cascade testing and reduce cancer morbidity and mortality. Our objective was to improve access via implementation of a different clinical model that designated appointments for patients seeking cascade testing. A secondary goal was to improve use of genetic counselor time. We implemented a dedicated Cascade Testing Clinic (CTC) with an expedited triaging and unique scheduling model to decrease patient wait time to appointment and optimize clinician time. We report on the process and outcomes here. Between October 2016 and February 2020, the average wait time between referral date and first scheduled appointment date was 46 days for the CTC compared to 144 days for the NPC (p < 0.0001). No-show/cancelation/rescheduling rate was 11.7% in the CTC compared to 29.7% in the NPC (p < 0.0001). Genetic counselors saw approximately twice as many patients per half-day clinic in the CTC compared to the NPC (p < 0.00001). Modifications to clinic staffing and appointment times were made based on provider feedback. Implementation of a dedicated clinic specifically for patients seeking cascade testing significantly shortened wait times for this population, reduced patient drop-off, and improved clinician efficiency. The relatively straightforward indications and generally uncomplicated medical histories made this an ideal population for expedited appointments.

Predicting Adverse Neonatal Outcomes for Preterm Neonates with Multi-Task Learning.

Diagnosis of adverse neonatal outcomes is crucial for preterm survival since it enables doctors to provide timely treatment. Machine learning (ML) algorithms have been demonstrated to be effective in predicting adverse neonatal outcomes. However, most previous ML-based methods have only focused on predicting a single outcome, ignoring the potential correlations between different outcomes, and potentially leading to suboptimal results and overfitting issues. In this work, we first analyze the correlations between three adverse neonatal outcomes and then formulate the diagnosis of multiple neonatal outcomes as a multi-task learning (MTL) problem. We then propose an MTL framework to jointly predict multiple adverse neonatal outcomes. In particular, the MTL framework contains shared hidden layers and multiple task-specific branches. Extensive experiments have been conducted using Electronic Health Records (EHRs) from 121 preterm neonates. Empirical results demonstrate the effectiveness of the MTL framework. Furthermore, the feature importance is analyzed for each neonatal outcome, providing insights into model interpretability.

Nirmatrelvir-ritonivir, COVID-19, and possible adverse cutaneous reactions.

Nirmatrelvir-ritonivir (Paxlovid) recently received emergency use authorization for the treatment of coronavirus disease 2019 (COVID-19). Literature has linked numerous cutaneous adverse effects to nirmatrelvir and ritonavir, the copackaged tablets within Paxlovid. A review and comparison of these adverse effects to the common cutaneous manifestations of COVID-19 is provided. Numerous drug-to-drug interactions exist between nirmatrelvir-ritonivir and commonly-used medications within dermatology.

Sexual orientation and gender identity (SOGI) data in dermatologic studies and opportunities for inclusion.

Dermatologists serve a vast array of patients with unique backgrounds. The National Institutes of Health (NIH) designated members of sexual and gender minorities as underrepresented in scholarly literature. Our study examines the past 10 years of studies published in highly-cited dermatologic journals, surveying each study for common data collection of sexual orientation and gender identity (SOGI) in dermatological studies. We found representation of sexual and gender minorities to be increasing in dermatological studies but recommend that SOGI data be collected regularly just as any other common variable in dermatological patient studies.

Searching for Answers: Information-Seeking by Young People At-Risk for Huntington's Disease.

BACKGROUND: Health information-seeking is a coping strategy used globally by individuals with a personal or family history of a medical condition, including Huntington's disease (HD). OBJECTIVE: We sought to ascertain information-seeking practices of young people who grew up at-risk for HD. METHODS: Participants ages 18-25 were recruited from HD support organizations. An online 96-item survey assessed information-seeking motivations and timing as well as information topics accessed, sources, and needs. RESULTS: Fifty young adults (mean age 22.2 years) who grew up at-risk for HD responded. HD had been generally kept a secret (35.4%) or talked about but difficult to bring up (43.8%) in many families. Most (78.0%) became aware of HD in their family before age 15. Few (7.1%) received information resources at the time of disclosure. Most (68.1%) first sought information independently online, half within a week of disclosure. Respondents were motivated to understand the potential impact of HD on their personal lives and family members, obtain general information about the condition, and learn about treatments and research. Most sought information on clinical features and inheritance with > 80% interested in information on symptoms and personal risk and > 70% about having children. CONCLUSION: Limited information is provided to young people when first informed about HD in their families leading to independent, mostly online information-seeking. Information is used to build knowledge about HD to facilitate coping and life planning. Healthcare providers can direct young people to reliable resources and guide parents in talking with children to ensure that information needs are met.