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1.
Dev Psychobiol ; 66(3): e22473, 2024 Apr.
Article En | MEDLINE | ID: mdl-38433422

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.


Brain , Social Behavior , Adolescent , Humans , Adult , Female , Male , Animals , Rats , Exploratory Behavior , Social Interaction , Dopamine , Neuronal Plasticity
2.
Curr Oncol Rep ; 26(1): 90-102, 2024 Jan.
Article En | MEDLINE | ID: mdl-38180691

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.


Frailty , Gastrointestinal Neoplasms , Humans , Aged , Frailty/diagnosis , Quality of Life , Frail Elderly , Gastrointestinal Neoplasms/diagnosis , Risk Assessment , Geriatric Assessment/methods
3.
Orthopedics ; 47(3): e139-e145, 2024.
Article En | MEDLINE | ID: mdl-38147496

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.].


Arthroplasty, Replacement, Hip , Osteoarthritis, Hip , Humans , Arthroplasty, Replacement, Hip/methods , Female , Male , Middle Aged , Retrospective Studies , Aged , Osteoarthritis, Hip/surgery , Osteoarthritis, Hip/diagnostic imaging , Hip Prosthesis , Hip Joint/surgery , Hip Joint/diagnostic imaging , Adult
4.
Cureus ; 15(5): e38690, 2023 May.
Article En | MEDLINE | ID: mdl-37292549

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.

5.
bioRxiv ; 2023 Apr 28.
Article En | MEDLINE | ID: mdl-37162856

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.

6.
bioRxiv ; 2023 May 03.
Article En | MEDLINE | ID: mdl-37205324

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.

7.
bioRxiv ; 2023 May 05.
Article En | MEDLINE | ID: mdl-37205376

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.

8.
bioRxiv ; 2023 May 03.
Article En | MEDLINE | ID: mdl-37205455

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.

9.
Arthroplasty ; 5(1): 18, 2023 Apr 02.
Article En | MEDLINE | ID: mdl-37004093

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.

10.
Arthroplasty ; 5(1): 2, 2023 Jan 03.
Article En | MEDLINE | ID: mdl-36593482

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.

11.
ASAIO J ; 69(5): 451-459, 2023 05 01.
Article En | MEDLINE | ID: mdl-36525671

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.


COVID-19 , Cardiopulmonary Resuscitation , Extracorporeal Membrane Oxygenation , Adult , Humans , Retrospective Studies , Catheterization
12.
Medicina (Kaunas) ; 58(3)2022 Mar 05.
Article En | MEDLINE | ID: mdl-35334565

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.


Fracture Fixation, Intramedullary , Tibial Fractures , Adolescent , External Fixators , Humans , Osteotomy/methods , Tibia/surgery , Tibial Fractures/complications , Tibial Fractures/surgery
13.
Article En | MEDLINE | ID: mdl-36732303

INTRODUCTION: Thumb carpometacarpal (CMC) joint dislocations are rare with minimal agreement on surgical management. The dorsoradial ligament (DRL) is the primary joint stabilizer but has not historically been reconstructed. We hypothesize that the reported reconstruction of first CMC joint dislocations primarily uses the flexor carpi radialis (FCR) without collective agreement on a surgical technique. METHODS: A systematic review of the PubMed database from 1996 to 2022 was done. Keywords were "thumb dislocation," "thumb carpometacarpal dislocation," and "carpometacarpal joint ligament repair." Inclusion criteria included isolated, unstable thumb CMC dislocations with reconstruction. The Preferred Reporting Items for Systematic Reviews and Meta Analyses guidelines were used. RESULTS: Four hundred thirty-seven records were identified, and nine met inclusion criteria. Two articles were cohort studies, and seven were case reports. Thirty-seven patients were included, and 26 patients had reconstruction with tendonous autograft. Twenty-five (96.2%) used the FCR and 1 (3.9%) from the palmaris longus. Three patients had reconstruction with a suture anchor. Surgical techniques varied between studies. DISCUSSION: The recommendation of the authors recreates the DRL during autograft repair. Current repair techniques that recreate the DRL use the FCR, but quantitative comparisons of tendonous autografts or suture anchors have not been done.


Carpometacarpal Joints , Joint Dislocations , Plastic Surgery Procedures , Humans , Carpometacarpal Joints/surgery , Thumb/surgery , Joint Dislocations/surgery , Ligaments, Articular/surgery
14.
Eur J Case Rep Intern Med ; 8(10): 002824, 2021.
Article En | MEDLINE | ID: mdl-34790624

BACKGROUND: Patients with sickle cell disease can experience various crises including sequestration crisis, haemolytic crisis and aplastic crisis. Due to alloantibody formation, transfusion alloantibodies can cause a haemolytic crisis. Treatment involves avoiding packed red blood cell transfusions, as well as intravenous immunoglobulin, steroids and eculizumab to decrease the chances of haemolysis. CASE DESCRIPTION: We report the case of a 42-year-old man who was found to have worsening anaemia after packed red blood cell transfusion with evidence suggestive of haemolytic crisis. Due to reticulocytopenia, aplastic crisis was also suspected and later confirmed via parvovirus IgG and IgM titres. The patient did not improve with steroid and intravenous immunoglobulin therapy and was treated with eculizumab as a salvage therapy. CONCLUSION: Concurrent hyper-haemolytic crisis and aplastic crisis should be suspected in patients with features of haemolysis and reticulocytopenia. Prompt recognition and treatment with eculizumab are paramount in those who fail steroid and intravenous immunoglobulin treatment. LEARNING POINTS: Treatment of hyper-haemolytic and aplastic crisis in sickle cell disease with eculizumab offers therapeutic benefit.A high index of suspicion for hyper-haemolytic crisis and aplastic crisis should be maintained in those with haemolytic features as well as reticulocytopenia in the setting of sickle cell disease.

15.
SAGE Open Med ; 9: 20503121211039105, 2021.
Article En | MEDLINE | ID: mdl-34422272

OBJECTIVES: Although there have been associations between diabetes and mortality in COVID-19 patients, it is unclear whether this is driven by the disease itself or whether it can be attributed to an inability to exhibit effective glucose control. METHODS: We conducted a retrospective cohort study of 292 patients admitted to a tertiary referral center to assess the association of mortality and glycemic control among COVID-19-positive patients. We used a logistic regression model to determine whether average fasting glycemic levels were associated with in-hospital mortality. RESULTS: Among the diabetic and non-diabetic patients, there were no differences between mortality or length of stay. Mean glucose levels in the first 10 days of admission were higher on average among those who died (150-185 mg/dL) compared with those who survived (125-165 mg/dL). When controlling for multiple variables, there was a significant association between mean fasting glucose and mortality (odds ratio = 1.014, p < 0.001). The associations between glucose and mortality remained when controlled for comorbidities and glucocorticoid use. CONCLUSION: The results of this retrospective study show an association between mortality and inpatient glucose levels, suggesting that there may be some benefit to tighter glucose control in patients diagnosed with COVID-19.

16.
Mol Brain ; 14(1): 101, 2021 06 29.
Article En | MEDLINE | ID: mdl-34187517

Mitochondrial function is required for brain energy homeostasis and neuroadaptation. Recent studies demonstrate that cocaine affects mitochondrial dynamics and morphological characteristics within the nucleus accumbens (NAc). Further, mitochondria are differentially regulated by cocaine in dopamine receptor-1 containing medium spiny neurons (D1-MSNs) vs dopamine receptor-2 (D2)-MSNs. However, there is little understanding into cocaine-induced transcriptional mechanisms and their role in regulating mitochondrial processes. Here, we demonstrate that cocaine enhances binding of the transcription factor, early growth response factor 3 (Egr3), to nuclear genes involved in mitochondrial function and dynamics. Moreover, cocaine exposure regulates mRNA of these mitochondria-associated nuclear genes in both contingent or noncontingent cocaine administration and in both rodent models and human postmortem tissue. Interestingly, several mitochondrial nuclear genes showed distinct profiles of expression in D1-MSNs vs D2-MSNs, with cocaine exposure generally increasing mitochondrial-associated nuclear gene expression in D1-MSNs vs suppression in D2-MSNs. Further, blunting Egr3 expression in D1-MSNs blocks cocaine-enhancement of the mitochondrial-associated transcriptional coactivator, peroxisome proliferator-activated receptor gamma coactivator (PGC1α), and the mitochondrial fission molecule, dynamin related protein 1 (Drp1). Finally, reduction of D1-MSN Egr3 expression attenuates cocaine-induced enhancement of small-sized mitochondria, causally demonstrating that Egr3 regulates mitochondrial morphological adaptations. Collectively, these studies demonstrate cocaine exposure impacts mitochondrial dynamics and morphology by Egr3 transcriptional regulation of mitochondria-related nuclear gene transcripts; indicating roles for these molecular mechanisms in neuronal function and plasticity occurring with cocaine exposure.


Cocaine/pharmacology , Early Growth Response Protein 3/genetics , Gene Expression Regulation , Mitochondrial Dynamics/genetics , Neurons/metabolism , Transcription, Genetic , Adult , Animals , Cell Nucleus/drug effects , Cell Nucleus/genetics , Early Growth Response Protein 3/metabolism , Female , Gene Expression Regulation/drug effects , Genes, Mitochondrial , Humans , Male , Mice, Inbred C57BL , Middle Aged , Mitochondrial Dynamics/drug effects , Neurons/drug effects , Nucleus Accumbens/metabolism , Promoter Regions, Genetic/genetics , Protein Binding/drug effects , RNA, Messenger/genetics , RNA, Messenger/metabolism , Ribosomes/metabolism , Transcription, Genetic/drug effects , Young Adult
17.
J Blood Med ; 12: 369-376, 2021.
Article En | MEDLINE | ID: mdl-34093048

BACKGROUND: Venous thromboembolism is a significant clinical event, with an annual incidence of 1-2 per 1000 population. Risk factors include recent surgery, prolonged immobility, oral contraceptive use, and active cancer. Inherited risks include protein C and S deficiencies, antithrombin deficiency, factor V Leiden mutation and prothrombin. These factors can be tested to guide therapy, but current evidence suggests that testing for inherited thrombophilia is not recommended in most inpatient settings. In the era of high value care, hypercoagulable testing for VTE creates a financial burden for the hospital and patients. We performed a retrospective chart review of hypercoagulable orders on VTE patients at our institution. METHODS: Institutional Review Board approval was obtained. A total of 287 adult patients admitted over a 3-month period with the diagnosis of VTE were included. Patients were identified via ICD-10 codes and data were collected from electronic medical records. Patient characteristics, provoked versus unprovoked VTE, and relative contraindications for hypercoagulability work-up were analyzed. Our primary outcome was to assess the appropriateness of thrombophilia testing in VTE patients based on screening guidelines. Our secondary outcome was to analyze the cost burden of ordering these tests. RESULTS: A total of 287 patients were included in our data analysis. Patient risk factors for VTE were malignancy, previous DVT, immobilization, surgery 3 months prior, and central line placement. Fifty-seven of 287 patients had at least one hypercoagulable test ordered during hospitalization which did not adhere to guidelines. Misuse of testing occurred during active thrombosis, active anticoagulation, presence of risk factors, first episode of VTE, and malignancy. The cost of ordering these 5 thrombophilia tests totaled over $40,000. CONCLUSION: In our study, numerous patients were tested without compliance to standard recommendations, which created financial and value-based burdens on our health care system. Increased awareness among clinicians is thus warranted to ensure high value care.

18.
J Clin Med Res ; 13(5): 283-292, 2021 May.
Article En | MEDLINE | ID: mdl-34104280

BACKGROUND: The objective of the study was to compare the renal outcomes in patients presenting with all-cause cardiogenic shock who were supported by either Impella devices (Abiomed, Danvers, MA), intra-aortic balloon pump (IABP), or vasopressors alone. Outcomes of cardiogenic shock remain poor even with the advancement of early revascularization and circulatory supportive care. Percutaneous mechanical circulatory support (MCS) device has emerged as an effective strategy in protecting end organ function especially renal function during high risk percutaneous coronary intervention (PCI) and in patients with cardiogenic shock. Currently, comparative data amongst various MCS modalities and their association with improvement of renal function in cardiogenic shock patients have not been well characterized. METHODS: Data from New Jersey Cardiac Catheterization Data registry of cardiogenic shock patients from a single tertiary care institution that underwent cardiac catheterization and the modality used to treat were obtained, either with Impella devices, IABP, or treatment with vasopressors alone. Retrospective chart review was conducted to assess the incidence of acute kidney injury (AKI) on patients with cardiogenic shock prior to and after cardiac catheterization and renal function was evaluated over the course of 96 h after cardiac catheterization. Statistical analysis was performed to ascertain significant difference in creatinine and estimated glomerular filtration rate (eGFR) in patients who received Impella devices, IABP, or were treated with vasopressors alone. RESULTS: A total of 61 all-cause cardiogenic shock patients met the inclusion and exclusion criteria and were included in the study with 19 receiving IABPs, 15 receiving Impella devices, and 27 treated with vasopressors alone. Baseline characteristics among these three groups did not show any statistically significant difference. A total of 29 cardiogenic shock patients had experienced AKI prior to cardiac catheterization in which those receiving Impella devices showed statistically significant decrease in creatinine and increase in eGFR at 72 and 96 h (P < 0.05) compared to baseline. Within the same cohort, Impella group showed statistically significant lower creatinine at 96 h when compared to IABP. Patients that experienced AKI after cardiac catheterization did not show any statistically significant changes in renal function regardless of modality used. CONCLUSION: The results of our study suggest that Impella devices improve renal function in all-cause cardiogenic shock patients who experience AKI prior to undergoing cardiac catheterization.

19.
Int Heart J ; 62(1): 175-177, 2021 Jan 30.
Article En | MEDLINE | ID: mdl-33455991

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.


Cardiac Output, Low/surgery , Coronary Artery Bypass, Off-Pump/instrumentation , Heart-Assist Devices/adverse effects , Aged , Cardiac Catheterization/methods , Cardiac Output, Low/diagnosis , Coronary Artery Bypass, Off-Pump/methods , Hemodynamics/physiology , Humans , Male , Perioperative Care/statistics & numerical data , Postoperative Complications/prevention & control , Risk Factors , Safety , Treatment Outcome
20.
J Am Acad Orthop Surg ; 29(2): e92-e97, 2021 Jan 15.
Article En | MEDLINE | ID: mdl-32568995

BACKGROUND: The purpose of this study was to compare the incidence of pseudotumors in metal-on-metal (MoM) titanium modular neck hip arthroplasties to non-MoM modular neck hip arthroplasties. A secondary goal was to determine whether a correlation exists between elevated metal concentrations and pseudotumor incidence. METHODS: The data were collected and evaluated from 49 MoM joints and 26 non-MoM joints between the years 2012 and 2017. Hip ultrasonography was done after a minimum of 5 years postimplantation. Whole serum metal (titanium, cobalt, and chromium) concentrations were measured at the hip ultrasonography study. RESULTS: The average time elapsed between surgery and ultrasonography visit was 7.6 years. In the 49 patients with MoM joints, 22.4% (n = 11) had a pseudotumor. In the 26 patients with non-MoM joints, 9.1% of metal-on-polyethylene hips (n = 1) and 0% of ceramic-on-ceramic/polyethylene hips developed a pseudotumor. No significant statistical correlation was observed between serum metal concentrations and pseudotumor formation (P > 0.05). A significant correlation was observed of serum titanium concentration to pseudotumor size (P = 0.024). CONCLUSION: The incidence of pseudotumor formation in MoM total hip arthroplasties was more than five times the incidence associated with non-MoM bearings. The correlation between serum titanium concentration and pseudotumor size suggests that titanium levels may be a useful indicator for pseudotumor formation in patients with this particular titanium modular neck femoral implant. No notable correlation was observed between serum cobalt and chromium concentration and pseudotumor formation or size.


Arthroplasty, Replacement, Hip , Hip Prosthesis , Metal-on-Metal Joint Prostheses , Arthroplasty, Replacement, Hip/adverse effects , Hip Prosthesis/adverse effects , Humans , Incidence , Metal-on-Metal Joint Prostheses/adverse effects , Prosthesis Design
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