Assessing Frailty in Gastrointestinal Cancer: Two Diseases in One?

PURPOSEOF REVIEW: This review examines the challenges of treating gastrointestinal cancer in the aging population, focusing on the importance of frailty assessment. Emphasized are the rise in gastrointestinal cancer incidence in older adults, advances in frailty assessments for patients with gastrointestinal cancer, the development of novel frailty markers, and a summary of recent trials. RECENT FINDINGS: Increasing evidence suggests that the use of a Comprehensive Geriatric Assessment (CGA) to identify frail older adults and individualize cancer care leads to lower toxicity and improved quality of life outcomes. However, the adoption of a full CGA prior to chemotherapy initiation in older cancer patients remains low. Recently, new frailty screening tools have emerged, including assessments designed to specifically predict chemotherapy-related adverse events. Additionally, frailty biomarkers have been developed, such as blood tests like IL-6 and performance tracking through physical activity monitors. The relevance of nutrition and muscle mass is discussed. Highlights from recent trials suggest the feasibility of successfully identifying patients most at risk of serious adverse events. There have been promising developments in identifying novel frailty markers and methods to screen for frailty in the older adult population. Further prospective trials that focus on and address the needs of the geriatric population for early identification of frailty in cancer care, facilitating a more tailored treatment approach. Practicing oncologists should select a frailty assessment to implement into their routine practice and adjust treatment accordingly.

Synaptic pruning during adolescence shapes adult social behavior in both males and females.

Evolutionarily conserved, peer-directed social behaviors are essential to participate in many aspects of human society. These behaviors directly impact psychological, physiological, and behavioral maturation. Adolescence is an evolutionarily conserved period during which reward-related behaviors, including social behaviors, develop via developmental plasticity in the mesolimbic dopaminergic "reward" circuitry of the brain. The nucleus accumbens (NAc) is an intermediate reward relay center that develops during adolescence and mediates both social behaviors and dopaminergic signaling. In several developing brain regions, synaptic pruning mediated by microglia, the resident immune cells of the brain, is important for normal behavioral development. We previously demonstrated that during adolescence, in rats, microglial synaptic pruning shapes the development of NAc and social play behavior in males and females. In this report, we hypothesize that interrupting microglial pruning in NAc during adolescence will have persistent effects on male and female social behavior in adulthood. We found that inhibiting microglial pruning in the NAc during adolescence had different effects on social behavior in males and females. In males, inhibiting pruning increased familiar exploration and increased nonsocial contact. In females, inhibiting pruning did not change familiar exploration behavior but increased active social interaction. This leads us to infer that naturally occurring NAc pruning serves to reduce social behaviors toward a familiar conspecific in both males and females.

Malunion of the Tibia: A Systematic Review.

Background and Objectives: Tibial malunions are defined as tibial fractures that have healed in a clinically unacceptable position, resulting in deformity such as shortening, lengthening, abnormal rotation, or angulation. These deformities can have adverse effects on patients, such as pain and gait disturbance, as well as long term development of post-traumatic arthritis. This paper seeks to highlight some of the options for surgical management of malunions and detail the strategies and approaches used to manage these complicated cases. Materials and Methods: An exhaustive search was conducted on PubMed using the key search terms "Tibial" OR "Tibia" AND "Malunion" to be included in the title. Exclusions to the search included any article with patients aged < 18 years, any nonhuman subjects, and any article not published or translated into English. Results: A systematic review of the literature revealed 26 articles encompassing 242 patients who had undergone surgical correction for tibia malunion. A total of 19 patients suffered from complications. Methods of treatment included osteotomies, with plate and screws, external fixator, angled blade plate, intramedullary nails, Ilizarov fixator, Taylor Spatial Frame, Precise nail, and total knee arthroplasty. Restoring alignment and the articular surface led to overwhelmingly positive patient outcomes. Conclusions: Tibial malunions take many forms, and as such, there are many approaches to correcting deformities. The literature supports the following radiological parameters to diagnose tibial malunion: 5−10 degrees angulation, 1−2 cm shortening, 10−15 degrees internal rotation, and 10−20 degrees external rotation. Surgical plans should be customized to each individual patient, as there are many approaches to tibial malunion that have been shown to be successful in delivering excellent clinical outcomes.

Clostridioides difficile Toxin A Remodels Membranes and Mediates DNA Entry Into Cells to Activate Toll-Like Receptor 9 Signaling.

BACKGROUND & AIMS: Clostridioides difficile toxin A (TcdA) activates the innate immune response. TcdA co-purifies with DNA. Toll-like receptor 9 (TLR9) recognizes bacterial DNA to initiate inflammation. We investigated whether DNA bound to TcdA activates an inflammatory response in murine models of C difficile infection via activation of TLR9. METHODS: We performed studies with human colonocytes and monocytes and macrophages from wild-type and TLR9 knockout mice incubated with TcdA or its antagonist (ODN TTAGGG) or transduced with vectors encoding TLR9 or small-interfering RNAs. Cytokine production was measured with enzyme-linked immunosorbent assay. We studied a transduction domain of TcdA (TcdA57-80), which was predicted by machine learning to have cell-penetrating activity and confirmed by synchrotron small-angle X-ray scattering. Intestines of CD1 mice, C57BL6J mice, and mice that express a form of TLR9 that is not activated by CpG DNA were injected with TcdA, TLR9 antagonist, or both. Enterotoxicity was estimated based on loop weight to length ratios. A TLR9 antagonist was tested in mice infected with C difficile. We incubated human colon explants with an antagonist of TLR9 and measured TcdA-induced production of cytokines. RESULTS: The TcdA57-80 protein transduction domain had membrane remodeling activity that allowed TcdA to enter endosomes. TcdA-bound DNA entered human colonocytes. TLR9 was required for production of cytokines by cultured cells and in human colon explants incubated with TcdA. TLR9 was required in TcdA-induced mice intestinal secretions and in the survival of mice infected by C difficile. Even in a protease-rich environment, in which only fragments of TcdA exist, the TcdA57-80 domain organized DNA into a geometrically ordered structure that activated TLR9. CONCLUSIONS: TcdA from C difficile can bind and organize bacterial DNA to activate TLR9. TcdA and TcdA fragments remodel membranes, which allows them to access endosomes and present bacterial DNA to and activate TLR9. Rather than inactivating the ability of DNA to bind TLR9, TcdA appears to chaperone and organize DNA into an inflammatory, spatially periodic structure.

Use of Impella CP Device in Off-Pump Coronary Artery Bypass Graft Surgery.

Off-pump coronary artery bypass grafting (OPCABG) may be performed on patients with high surgical risk who are poor candidates for traditional mechanical circulatory support. Hemodynamic support with micro-axial mechanical circulatory devices has been performed with limited but promising results.We report a case of a 66-year-old male with multiple comorbidities and low cardiac output undergoing OPCABG. Impella CP device was deployed for "in-pump" support during surgical coronary revascularization resulting in intraoperative stability and uncomplicated post-operative recovery.Previous reports have described the use of the Impella Recover LP 5.0 device for use during OPCABG. We describe the successful and safe perioperative use of the Impella CP device. Despite lower flow rates, adequate support was achieved and the transfemoral cannulation and smaller outer diameter than the Impella 5.0 device may decrease the risk of complications and expedite recovery. Further research will be necessary to determine the optimal perioperative hemodynamic support strategy to offer hemodynamically unstable, high, and prohibitive risk patients.

Identifying Barriers to the Treatment of Chronic Hepatitis C Infection.

BACKGROUND AND AIMS: Chronic hepatitis C (CHC) viral infection has a major impact on our health care system. The emergence of direct-acting antiviral agents (DAA) has made treatment simple (oral), efficacious, and safe. However, treatment is expensive and access is variable. Despite great treatment outcomes, only a minority of patients with CHC receive antiviral therapy. This study identifies the barriers to treatment in CHC infection. METHODS: Study recruited all hepatitis C antibody-positive patients between 2012 and 2016 from a large academic teaching hospital in New York City. Demographic information, clinical data, and insurance information were reviewed. Statistical analysis performed with OR and p < 0.05 reported. RESULT: A total of 1,548 patients with hepatitis C antibody-positive titer were included in the initial analysis. One thousand and twenty-four patients were forwarded to the final analysis after exclusion of 524 patients (for distant resolved hepatitis C viral [HCV] infection [n = 42], patients cured with interferon-based regimens [n = 94], patients with comorbid conditions [n = 176], and patients with an incomplete medical chart [n = 212]). In the intention to treat cohort of 1,024 patients, 204 patients achieved a sustained virological response after receiving DAAs (n = 204/1,024 - 20%). The majority of patients had not received DAAs (n = 816/1,024 patients - 80%). Multiple factors resulted in hepatitis C viral infection (HCV) patients not receiving DAAs including the following primary factors: (a) lost to follow-up clinic visits and poor adherence to clinic appointments (n = 548 [67%]; p value <0.0001), (b) active substance abuse (alcoholism and IV drug abuse; n = 165 [20%]; p value 0.22), (c) patients with significant psychiatric illness (n = 103 [12.7%]; p value 0.015), and subgroup analysis revealed that 188 (188/1,024 - 12%) patients had human immunodeficiency virus-1 (HIV-1) and HCV coinfection. Majority of HCV/HIV coinfected patients had not received DAAs (n = 176 [97%]; p value <0.0001, OR 4.46). The etiology of nontreatment in coinfected HIV/HCV patients was 73.3% poor adherence, 11.5% active substance abuse including alcohol and IV drug use, and 9% significant psychiatric illness and 6.2% multiple reasons for not receiving HCV treatment. CONCLUSION: Multifactorial barriers are preventing hepatitis C patients from receiving effective DAA therapy. Primary factors include poor compliance, substance abuse, and significant psychiatric illness, with significant overlap between these groups. Subgroup analysis showed a substantial number of high-risk patients with HIV/HCV coinfection did not receive DAA therapy. A multidisciplinary clinic approach with a hepatologist, ID physicians, social worker, and behavioral health psychologist and case manager should provide a solution to improve diagnosis and treatment with DAA.

From ideation to practice: How pharmacists and students can leverage hackathons and innovation labs to accelerate innovation in pharmacy.

OBJECTIVES: To describe novel methods regarding innovation for pharmacists and student pharmacists to leverage local and national events, such as hackathons and innovation labs, that provide guidance and resources for developing novel products and solutions in health care. DATA SOURCES: Not applicable. SUMMARY: The profession of pharmacy exists in a diverse and complex system where collaboration is essential for innovation and can leverage existing resources to accelerate this. Hackathons occur over one or more days and offer a venue and resources to support innovation as interprofessional teams develop and pitch new product ideas for potential investment. Innovation labs serve as more permanent locations that offer resources and expertise to help realize ideas and guide development into potentially viable solutions and products for health care. CONCLUSION: Although currently hosted hackathons and design spaces may prove to be beneficial to pharmacists looking to innovate, they are frequently located in urban areas or large academic institutions that are not readily accessible to the larger pharmacy community. Fostering opportunities, whether as local hackathons or innovation labs, can potentially help to accelerate the innovation cycle for the pharmacy profession. These resources can be developed in local communities or through national pharmacy societies and organizations to increase access.

Study of Correlation between Diabetic Pulmonopathy with Serum Adiponectin Levels in Patients of Type 2 Diabetes Mellitus.

Diabetes mellitus a disease with various macro and micro vascular complications due to its various metabolic dysregulations, is well known to involve lungs in long run in both type 1 and 2 diabetes mellitus, causing tremendous burden on health care system. Common simple lung function tests alone are likely to underestimate the prevalence and degree of lung dysfunction in diabetes, but newer noninvasive tests of lung mechanical function provide a more sensitive assessment of peripheral airway function, hence by establishing a marker and risk factors for pulmonary involvement in diabetic individuals, cases with high risk for pulmonary involvement can be found before hand and proper medical therapy can be started for primary prophylaxis of same, Hence in this study we tried to find out any correlation between serum adiponectin levels and pulmonary dysfunction in patients of type 2 diabetes mellitus, which shows a significant role of adiponectin as early marker of the disease with p value of 0.04, the decrease in serum adiponectin level is also associated with more severe disease, hence adiponectin levels can be used as early markers of pulmonary dysfunction in diabetic patients.

A multicenter, retrospective, case-cohort study of the epidemiology and risk factors for Clostridium difficile infection among cord blood transplant recipients.

BACKGROUND: Clostridium difficile infection (CDI) is the leading cause of health-care associated infectious diarrhea. The aim of this study was to evaluate the epidemiology and risk factors for CDI in the 100 days following umbilical cord blood transplantation (UCBT) at three Boston hospitals. METHODS: We performed a multicenter, retrospective, case-cohort study of 226 UCBT recipients at Beth Israel Deaconess Medical Center, Massachusetts General Hospital, and Dana Farber/Brigham and Women's Cancer Center from 2003 to 2012. CDI was defined as diarrhea (≥3 unformed bowel movements for at least 2 days) plus a positive stool test for toxinogenic C. difficile and not attributed to any other cause. RESULTS: Among 226 UCBT recipients, 22 patients (9.7%) developed CDI within the first 100 days of transplant (corresponding to an infection rate of 10.8 cases per 10 000 person-days). The 100-day and 1-year rates were stable across the time period and between institutions. UCBT recipients with CDI were more likely than non-CDI patients to be older, with higher body mass indices, and to have received an antipseudomonal penicillin agent. In a time-dependent case-cohort analysis of the risk factors associated with CDI in the first 100 days after UCBT, bacterial infection after UCBT was the strongest risk factor for CDI (hazard ratio 2.8; 95% confidence interval 1.08-7.24; P=.03), after adjustment for transplant variables including antibiotic exposure. CONCLUSION: This study verifies the previously reported risk factors for CDI including older age and antibiotic exposure and identifies a novel association between bacterial infections and risk for CDI.

Comparison of 3-Dimensional Computed Tomography-Based Measurement of Glenoid Bone Loss With Arthroscopic Defect Size Estimation in Patients With Anterior Shoulder Instability.

PURPOSE: The purpose of this study was to compare four 3-dimensional (3D) computed tomography (CT) methods of measuring glenoid bone loss with the arthroscopic estimation of glenoid bone loss. METHODS: Twenty patients with recurrent anterior shoulder instability underwent bilateral shoulder CT scans and were found to have glenoid bone loss. Arthroscopic estimation of glenoid bone loss was performed in all patients. Three-dimensional CT reconstruction was performed on the CT scans of each patient. The glenoid bone loss of each patient was measured using the surface area, Pico, ratio, and anteroposterior distance-from-bare area methods. The mean percent loss calculated with each method was compared with arthroscopy to determine the reliability of arthroscopy in the measurement of glenoid bone loss. RESULTS: The mean percent bone loss calculated with arthroscopic estimation, surface area, Pico, ratio, and anteroposterior distance-from-bare area methods was 18.13% ± 11.81%, 12.15% ± 8.50% (P = .005), 12.77% ± 8.17% (P = .002), 9.50% ± 8.74% (P < .001), and 12.44% ± 10.68% (P = .001), respectively. Repeated-measures analysis of variance showed that the 3D CT methods and arthroscopy were significantly different (F4,76 = 13.168, P = .02). The estimate using arthroscopy is 55% greater than the average of the 3D CT methods. CONCLUSIONS: Our findings suggest that arthroscopy significantly overestimates glenoid bone loss compared with CT and call into question its validity as a method of measurement. A more internally consistent and accurate method for the measurement of glenoid bone loss is necessary to appropriately diagnose and treat shoulder instability. LEVEL OF EVIDENCE: Level IV, case series.

A Novel Digital Templating Method for Total Hip Arthroplasty in Patients With Unilateral Hip Arthrosis.

BACKGROUND: Identification of the hip center of rotation (HCOR) before total hip arthroplasty (THA) is crucial for achieving optimal implant position and size, and for restoring native biomechanics around the hip joint. Current techniques for determining the HCOR in cases of abnormal hip anatomy are limited and unreliable. This study presents a novel technique using open-access software for preoperative THA templating for patients with significantly abnormal hip anatomy due to unilateral hip arthrosis. The aim is to reliably predict the HCOR and acetabular implant size compared with a traditional intraoperative method. MATERIALS AND METHODS: This retrospective study involved 20 patients with unilateral hip arthrosis who underwent THA. Preoperative templating was performed using the experimental technique, and the position of the HCOR was measured on preoperative and postoperative radiographs. The positions of the predicted and actual HCOR were compared, along with the inclination and size of the acetabular component. RESULTS: The difference between the predicted and actual HCOR positions was insignificant (0.43±0.22 mm vertically and 0.18±0.20 mm horizontally), and there was a positive correlation between them (r=0.78, P<.005; r=0.72, P<.005). The agreement between the predicted and actual acetabular implant sizes was 85%, with near-perfect interobserver agreement (Cohen's kappa=0.827). CONCLUSION: This novel technique provides a reliable method for predicting HCOR and acetabular implant size for THA in cases of unilateral hip arthrosis. This technique may help optimize biomechanics and improve outcomes in challenging cases. Further research and validation are warranted to establish its broader applicability. [Orthopedics. 2024;47(3):e139-e145.].

Exogenous modification of platelet membranes with the omega-3 fatty acids EPA and DHA reduces platelet procoagulant activity and thrombus formation.

Several studies have implicated the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in inhibition of normal platelet function, suggesting a role for platelets in EPA- and DHA-mediated cardioprotection. However, it is unclear whether the cardioprotective mechanisms arise from alterations to platelet-platelet, platelet-matrix, or platelet-coagulation factor interactions. Our previous results led us to hypothesize that EPA and DHA alter the ability of platelets to catalyze the generation of thrombin. We tested this hypothesis by exogenously modifying platelet membranes with EPA and DHA, which resulted in compositional changes analogous to increased dietary EPA and DHA intake. Platelets treated with EPA and DHA showed reductions in the rate of thrombin generation and exposure of platelet phosphatidylserine. In addition, treatment of platelets with EPA and DHA decreased thrombus formation and altered the processing of thrombin precursor proteins. Furthermore, treatment of whole blood with EPA and DHA resulted in increased occlusion time and a sharply reduced accumulation of fibrin under flow conditions. These results demonstrate that EPA and DHA inhibit, but do not eliminate, the ability of platelets to catalyze thrombin generation in vitro. The ability of EPA and DHA to reduce the procoagulant function of platelets provides a possible mechanism behind the cardioprotective phenotype in individuals consuming high levels of EPA and DHA.

Microglia-mediated synaptic pruning in the nucleus accumbens during adolescence: A preliminary study of the proteomic consequences and putative female-specific pruning target.

Adolescence is a period of copious neural development, particularly in the 'reward' circuitry of the brain, and reward-related behavioral development, including social development. One neurodevelopmental mechanism that appears to be common across brain regions and developmental periods is the requirement for synaptic pruning to produce mature neural communication and circuits. We published that microglia-C3-mediated synaptic pruning also occurs in the nucleus accumbens (NAc) reward region during adolescence to mediate social development in male and female rats. However, both the adolescent stage in which microglial pruning occurred, and the synaptic pruning target, were sex specific. NAc pruning occurred between early and mid-adolescence in male rats to eliminate dopamine D1 receptors (D1rs), and between pre- and early adolescence in female rats (P20-30) to eliminate an unknown, non-D1r target. In this report, we sought to better understand the proteomic consequences of microglial pruning in the NAc, and what the female pruning target might be. To do this, we inhibited microglial pruning in the NAc during each sex's pruning period and collected tissue for mass spectrometry proteomic analysis and ELISA validation. We found that the proteomic consequences of inhibiting microglial pruning in the NAc were inversely proportional between the sexes, and a novel, female-specific pruning target may be Lynx1. Please note, if this preprint will be pushed further to publication it will not be by me (AMK), as I am leaving academia. So, I'm going to write more conversationally.

Anorectal Gastrointestinal Stromal Tumor: Report of a Rare Case.

Gastrointestinal stromal tumors (GIST) are mesenchymal spindle cell tumors of the gastrointestinal tract with the rarest occurrence in anal canal sites accounting for approximately only 2-8% of the anorectal GISTs. GISTs involve the expression of KIT (CD117) tyrosine kinase with the presence of mutations in KIT or platelet-derived growth factor alpha (PDGFRα) and are identified as an important target in therapy. The elderly population in the age of 70s appears to be at the highest risk with abdominal pain, GI bleeding, anemia, or weight loss as non-specific presenting symptoms. Here, we describe a case of a 56-year-old man who presented with vague dull pain in his left buttock diagnosed with GIST with a submucosal mass in the posterior wall of the anal canal and rectum and a tumor size of 45x42x37 mm. An immunohistological study of the biopsy sample reported positive for CD 117, CD 34, and DOG 1. The patient was prescribed neoadjuvant imatinib for 8 months with a good response and subsequently underwent transanal endoscopic microsurgical resection. Post-operatively, the patient was continued on adjuvant imatinib followed by regular restaging CT chest/abdomen/pelvis and surveillance flexible sigmoidoscopy every 6 months.

Epidemiology of total hip arthroplasty: demographics, comorbidities and outcomes.

BACKGROUND: Primary THA (THA) is a successful procedure for end-stage hip osteoarthritis. In the setting of a failed THA, revision total hip arthroplasty (rTHA) acts as a salvage procedure. This procedure has increased risks, including sepsis, infection, prolonged surgery time, blood loss, and increased length of stay. Increasing focus on understanding of demographics, comorbidities, and inpatient outcomes can lead to better perioperative optimization and post-operative outcomes. This epidemiological registry study aimed to compare the demographics, comorbidity profiles, and outcomes of patients undergoing THA and rTHA. METHODS: A retrospective review of discharge data reported from 2006 to the third quarter of 2015 using the National Inpatient Sample registry was performed. The study included adult patients aged 40 and older who underwent either THA or rTHA. A total of 2,838,742 THA patients and 400,974 rTHA patients were identified. RESULTS: The primary reimbursement for both THA and rTHA was dispensed by Medicare at 53.51% and 65.36% of cases respectively. Complications arose in 27.32% of THA and 39.46% of rTHA cases. Postoperative anemia was the most common complication in groups (25.20% and 35.69%). Common comorbidities in both groups were hypertension and chronic pulmonary disease. rTHA indications included dislocation/instability (21.85%) followed by mechanical loosening (19.74%), other mechanical complications (17.38%), and infection (15.10%). CONCLUSION: Our data demonstrated a 69.50% increase in patients receiving THA and a 28.50% increase in rTHA from the years 2006 to 2014. The data demonstrated 27.32% and 39.46% complication rate with THA and rTHA, with postoperative anemia as the most common cause. Common comorbidities were hypertension and chronic pulmonary disease. Future analyses into preoperative optimizations, such as prior consultation with medical specialists or improved primary hip protocol, should be considered to prevent/reduce postoperative complications amongst a progressive expansion in patients receiving both THA and rTHA.

Impaired microglia-mediated synaptic pruning in the nucleus accumbens during adolescence results in persistent dysregulation of familiar, but not novel social interactions in sex-specific ways.

Evolutionarily conserved, peer-directed social behaviors are essential to participate in many aspects of human society. These behaviors directly impact psychological, physiological, and behavioral maturation. Adolescence is an evolutionarily conserved period during which reward-related behaviors, including social behaviors, develop via developmental plasticity in the mesolimbic dopaminergic 'reward' circuitry of the brain. The nucleus accumbens (NAc) is an intermediate reward relay center that develops during adolescence and mediates both social behaviors and dopaminergic signaling. In several developing brain regions, synaptic pruning mediated by microglia, the resident immune cells of the brain, is important for normal behavioral development. In rats, we previously demonstrated that microglial synaptic pruning also mediates NAc and social development during sex-specific adolescent periods and via sex-specific synaptic pruning targets. In this report, we demonstrate that interrupting microglial pruning in NAc during adolescence persistently dysregulates social behavior towards a familiar, but not novel social partner in both sexes, via sex-specific behavioral expression. This leads us to infer that naturally occurring NAc pruning serves to reduce social behaviors primarily directed toward a familiar conspecific in both sexes, but in sex-specific ways.

Microglial synaptic pruning in the nucleus accumbens during adolescence sex-specifically influences splenic immune outcomes.

Strong social support promotes a variety of positive health outcomes in humans and rodent models, while social isolation in rodents shortens lifespan, perceived social isolation (i.e. loneliness) can increase mortality by up to 50% in humans. How social relationships lead to these drastic health effects is unclear, but may involve modulation of the peripheral immune system. The reward circuitry of the brain and social behaviors undergo a critical period of development during adolescence. We published that microglia-mediated synaptic pruning occurs in the nucleus accumbens (NAc) reward region during adolescence to mediate social development in male and female rats. We hypothesized that if reward circuitry activity and social relationships directly impact the peripheral immune system, then natural developmental changes in the reward circuitry and social behaviors during adolescence should also directly impact the peripheral immune system. To test this, we inhibited microglial pruning in the NAc during adolescence, and then collected spleen tissue for mass spectrometry proteomic analysis and ELISA validation. We found that the global proteomic consequences of inhibiting microglial pruning in the NAc were similar between the sexes, but target-specific examination suggests that NAc pruning impacts Th1 cell-related immune markers in the spleen in males, but not females, and broad neurochemical systems in the spleen in females, but not males.

Epidemiology of primary and revision total knee arthroplasty: analysis of demographics, comorbidities and outcomes from the national inpatient sample.

INTRODUCTION: Primary total knee arthroplasty (TKA) is a preferred treatment for end-stage knee osteoarthritis. In the setting of a failed TKA, revision total knee arthroplasty (rTKA) acts as a salvage procedure and carries a higher risk compared to primary TKA. Given increased interest in postoperative outcomes from these procedures, a thorough understanding of the demographics, comorbidities, and inpatient outcomes is warranted. This study aimed to report the epidemiological data of demographics, comorbidity profiles and outcomes of patients undergoing TKA and rTKA. METHODS: A retrospective review of NIS registry discharge data from 2006 to 2015 third quarter was performed. This study included adults aged 40 and older who underwent TKA or rTKA. A total of 5,901,057 TKA patients and 465,968 rTKA patients were included in this study. Simple descriptive statistics were used to present variables on demographics, medical comorbidities, and postoperative complications. RESULTS: A total of 5,901,057 TKA and 465,968 rTKA discharges were included in this study, with an average age of 66.30 and 66.56 years, and the major payor being Medicare, accounting for 55.34% and 59.88% of TKA and rTKA cases, respectively. Infection (24.62%) was the most frequent reason for rTKA, and was followed by mechanical complications (18.62%) and dislocation (7.67%). The most common medical comorbidities for both groups were hypertension, obesity, and diabetes. All types of inpatient complications were reported in 22.21% TKA and 28.78% of rTKA cases. Postoperative anemia was the most common complication in both groups (20.34% vs. 25.05%). CONCLUSIONS: Our data demonstrated a 41.9% increase in patients receiving TKA and 28.8% increase in rTKA from the years 2006 to 2014. The data showed a 22.21% and a 28.78% "complication" rate with TKA and rTKA, with postoperative anemia being the most common complication. The top 3 medical comorbidities were hypertension, obesity, and diabetes for both groups and with increased focus on perioperative optimization, future analyses into preoperative medical optimization, and improved primary arthroplasty protocol may result in improved postoperative outcomes.

Social aging trajectories are sex-specific, sensitive to adolescent stress, and most robustly revealed during social tests with familiar stimuli.

Social networks and support are integral to health and wellness across the lifespan, and social engagement may be particularly important during aging. However, social behavior and social cognition decline naturally during aging across species. Social behaviors are in part supported by the 'reward' circuitry, a network of brain regions that develops during adolescence. We published that male and female rats undergo adolescent social development during sex-specific periods, pre-early adolescence in females and early-mid adolescence males. Although males and females have highly dimorphic development, expression, and valuation of social behaviors, there is relatively little data indicating whether social aging is the same or different between the sexes. Thus, we sought to test two hypotheses: (1) natural social aging will be sex-speciifc, and (2) social isolation stress restricted to sex-specific adolescent critical periods for social development would impact social aging in sex-specific ways. To do this, we bred male and female rats in-house, and divided them randomly to receive either social isolation for one week during each sex's respective critical period, or no manipulation. We followed their social aging trajectory with a battery of five tests at 3, 7, and 11 months of age. We observed clear social aging signatures in all tests administered, but sex differences in natural social aging were most robustly observed when a familiar social stimulus was included in the test. We also observed that adolescent isolation did impact social behavior, in both age-independent and age-dependent ways, that were entirely sex-specific. Please note, this preprint will not be pushed further to publication (by me, AMK), as I am leaving academia. So, it's going to be written more conversationally.

An Intensivist-Led Extracorporeal Membrane Oxygenation Program: Design, Implementation, and Outcomes of the First Five Years.

We describe the development, implementation, and outcomes of an intensivist-led adult extracorporeal life support (ECLS) program using intensivists both to perform venovenous (V-V), venoarterial (V-A), and extracorporeal cardiopulmonary resuscitation (ECPR) cannulations, and to manage patients on ECLS throughout their ICU course. All adults supported with ECLS at the University of New Mexico Hospital (UNMH) from February 1, 2017 to December 31, 2021 were retrospectively analyzed. A total of 203 ECLS cannulations were performed in 198 patients, including 116 V-A cannulations (including 65 during ECPR) and 87 V-V cannulations (including 38 in patients with COVID-19). UNMH intensivists performed 195 cannulations, with 9 cannulation complications. Cardiothoracic surgeons performed 8 cannulations. Overall survival to hospital discharge or transfer was 46.5%. Survival was 32.3% in the ECPR group and 56% in the non-ECPR V-A group. In the V-V cohort, survival was 66.7% in the COVID-19-negative patients and 34.2% in the COVID-19-positive patients. This large series of intensivist-performed ECLS cannulations-including V-A, V-V, and ECPR modalities-demonstrates the successful implementation of a comprehensive intensivist-led ECLS program. With outcomes comparable to those in the literature, our program serves as a model for the initiation and development of ECLS programs in settings with limited access to local subspecialty cardiothoracic surgical services.