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1.
Cureus ; 16(6): e63409, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39070418

RESUMEN

Implantable medical devices, such as pacemakers, have significantly improved the quality of life for patients with cardiac conditions, allowing them to maintain active lifestyles. Nonetheless, these devices can present unique challenges when interacting with the wearer's physical activities, potentially leading to unforeseen complications. Here, we present a case of an 81-year-old male golfer, with a history of atrial fibrillation, congestive heart failure, and sick sinus syndrome, who experienced atrial lead noise from his pacemaker, exclusively triggered by his golf swing. This incident, which led to multiple interventions including lead extraction, reimplantation, and eventually a switch to a unipolar lead configuration, represents the first documented case of its kind. It underscores the intricate relationship between the biomechanical forces of certain sports and the functionality of implanted cardiac devices. Through detailed electrophysiology testing, this case demonstrates how specific movements inherent to the patient's golf swing could induce micro-damage to the pacemaker leads, causing noise and malfunction. The findings from this case emphasize the need for healthcare providers to perform sport-specific biomechanical evaluations and create tailored rehabilitation strategies that consider the unique physical demands placed on patients with implanted devices. This approach is important not only for diagnosing and managing similar cases but also for advancing our understanding of how to best support the active lifestyles of patients with implanted cardiac devices, ensuring their safety and longevity.

2.
JAMA Intern Med ; 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39073805

RESUMEN

This Viewpoint proposes a messaging framework called CREATE TRUST to improve written communication with patients.

3.
Equine Vet J ; 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38924597

RESUMEN

BACKGROUND: Bisphosphonates are widely used in equine athletes to reduce lameness associated with skeletal disorders. Widespread off-label use has led to concern regarding potential negative effects on bone healing, but little evidence exists to support or refute this. OBJECTIVES: To investigate the influence of clinically relevant doses of tiludronate on bone remodelling and bone healing. STUDY DESIGN: Randomised, controlled in vivo experiments. METHODS: Each horse had a single tuber coxae biopsied (Day 0), then were divided into a treatment (IV tiludronate) or control (IV saline) group. Treatments were administered 30 and 90 days following initial biopsy. Biopsy of the tuber coxae was repeated on Day 60 to evaluate bone healing following a single treatment. Oxytetracycline was administered on Days 137 and 147 to label bone formation. The contralateral tuber coxae was biopsied on Day 150 to evaluate effects of repeated treatment. Bone biopsies were evaluated with micro-computed tomography and/or dynamic histomorphometry using standard techniques. RESULTS: Nineteen horses completed the study, with no complications following the biopsies and treatments. No significant differences in the trabecular bone parameters or bone formation rate were observed between treatment groups. MAIN LIMITATIONS: The use of a first-generation bisphosphonate may mean some effects of these drugs are underrepresented using this model. The results pertain to the tuber coxae and may not reflect injury or the healing response that occurs in long bones in training or racing. CONCLUSIONS: In this model, tiludronate did not affect normal bone remodelling in the horse, despite repeat dosages.

4.
JAMA Health Forum ; 5(6): e241653, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38941086

RESUMEN

Importance: Despite growing interest in psychedelics, there is a lack of routine population-based surveillance of psychedelic microdosing (taking "subperceptual" doses of psychedelics, approximately one-twentieth to one-fifth of a full dose, over prolonged periods). Analyzing Google search queries can provide insights into public interest and help address this gap. Objective: To analyze trends in public interest in microdosing in the US through Google search queries and assess their association with cannabis and psychedelic legislative reforms. Design, Setting, and Participants: In this cross-sectional study, a dynamic event-time difference-in-difference time series analysis was used to assess the impact of cannabis and psychedelic legislation on microdosing search rates from January 1, 2010, to December 31, 2023. Google search rates mentioning "microdosing," "micro dosing," "microdose," or "micro dose" within the US and across US states were measured in aggregate. Exposure: Enactment of (1) local psychedelic decriminalization laws; (2) legalization of psychedelic-assisted therapy and statewide psychedelic decriminalization; (3) statewide medical cannabis use laws; (4) statewide recreational cannabis use laws; and (5) all cannabis and psychedelic use restricted. Main Outcome and Measures: Microdosing searches per 10 million Google queries were measured, examining annual and monthly changes in search rates across the US, including frequency and nature of related searches. Results: Searches for microdosing in the US remained stable until 2014, then increased annually thereafter, with a cumulative increase by a factor of 13.4 from 2015 to 2023 (7.9 per 10 million to 105.6 per 10 million searches, respectively). In 2023, there were 3.0 million microdosing searches in the US. Analysis at the state level revealed that local psychedelic decriminalization laws were associated with an increase in search rates by 22.4 per 10 million (95% CI, 7.5-37.2), statewide psychedelic therapeutic legalization and decriminalization were associated with an increase in search rates by 28.9 per 10 million (95% CI, 16.5-41.2), statewide recreational cannabis laws were associated with an increase in search rates by 40.9 per 10 million (95% CI, 28.6-53.3), and statewide medical cannabis laws were associated with an increase in search rates by 11.5 per 10 million (95% CI, 6.0-16.9). From August through December 2023, 27.0% of the variation in monthly microdosing search rates between states was explained by differences in cannabis and psychedelics legal status. Conclusion and Relevance: This cross-sectional study found that state-led legislative reforms on cannabis and psychedelics were associated with increased public interest in microdosing psychedelics.


Asunto(s)
Cannabis , Alucinógenos , Legislación de Medicamentos , Alucinógenos/administración & dosificación , Humanos , Estados Unidos , Estudios Transversales
5.
Adv Sci (Weinh) ; : e2309509, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38884139

RESUMEN

Dermal tattoo biosensors are promising platforms for real-time monitoring of biomarkers, with skin used as a diagnostic interface. Traditional tattoo sensors have utilized small molecules as biosensing elements. However, the rise of synthetic biology has enabled the potential employment of engineered bacteria as living analytical tools. Exploiting engineered bacterial sensors will allow for potentially more sensitive detection across a broad biomarker range, with advanced processing and sense/response functionalities using genetic circuits. Here, the interfacing of bacterial biosensors as living analytics in tattoos is shown. Engineered bacteria are encapsulated into micron-scale hydrogel beads prepared through scalable microfluidics. These biosensors can sense both biochemical cues (model biomarkers) and biophysical cues (temperature changes, using RNA thermometers), with fluorescent readouts. By tattooing beads into skin models and confirming sensor activity post-tattooing, our study establishes a foundation for integrating bacteria as living biosensing entities in tattoos.

6.
Calcif Tissue Int ; 115(2): 174-184, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38856730

RESUMEN

Patients with chronic kidney disease (CKD) report high pain levels, but reduced renal clearance eliminates many analgesic options; therefore, 30-50% of CKD patients have chronic opioid prescriptions. Opioid use in CKD is associated with higher fracture rates. Opioids may directly alter bone turnover directly through effects on bone cells and indirectly via increasing inflammation. We hypothesized that continuous opioid exposure would exacerbate the high bone turnover state of CKD and be associated with elevated measures of inflammation. Male C57Bl/6J mice after 8 weeks of adenine-induced CKD (AD) and non-AD controls (CON) had 14-day osmotic pumps (0.25-µL/hr release) containing either saline or 50-mg/mL oxycodone (OXY) surgically implanted in the subscapular region. After 2 weeks, all AD mice had elevated blood urea nitrogen, parathyroid hormone, and serum markers of bone turnover compared to controls with no effect of OXY. Immunohistochemical staining of the distal femur showed increased numbers of osteocytes positive for the mu opioid and for toll-like receptor 4 (TLR4) due to OXY. Osteocyte protein expression of tumor necrosis factor-α (TNF-α) and RANKL were higher due to both AD and OXY so that AD + OXY mice had the highest values. Trabecular osteoclast-covered surfaces were also significantly higher due to both AD and OXY, resulting in AD + OXY mice having 4.5-fold higher osteoclast-covered surfaces than untreated CON. These data demonstrate that opioids are associated with a pro-inflammatory state in osteocytes which increases the pro-resorptive state of CKD.


Asunto(s)
Adenina , Analgésicos Opioides , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Osteoclastos , Insuficiencia Renal Crónica , Animales , Adenina/farmacología , Adenina/efectos adversos , Masculino , Insuficiencia Renal Crónica/inducido químicamente , Insuficiencia Renal Crónica/metabolismo , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Analgésicos Opioides/efectos adversos , Ratones , Inflamación , Remodelación Ósea/efectos de los fármacos , Oxicodona/farmacología , Huesos/metabolismo , Huesos/efectos de los fármacos
7.
ACS Med Chem Lett ; 15(6): 879-884, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38894928

RESUMEN

Methodology is described for the synthesis of C6 derivatives of raloxifene, a prescribed drug for the treatment and prevention of osteoporosis. Studies have explored the incorporation of electron-withdrawing substituents at C6 of the benzothiophene core. Efficient processes are also examined to introduce hydrogen bond donor and acceptor functionality. Raloxifene derivatives are evaluated with in vitro testing to determine estrogen receptor (ER) binding affinity and gene expression in MC3T3 cells.

8.
Resuscitation ; 200: 110244, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38762082

RESUMEN

BACKGROUND: Frailty is associated with increased 30-day mortality and non-home discharge following perioperative cardiac arrest. We estimated the predictive accuracy of frailty when added to baseline risk prediction models. METHODS: In this retrospective cohort study using 2015-2020 NSQIP data for 3048 patients aged 50+ undergoing non-cardiac surgery and resuscitation on post-operative day 0 (i.e., intraoperatively or postoperatively on the day of surgery), baseline models including age, sex, ASA physical status, preoperative sepsis or septic shock, and emergent surgery were compared to models that added frailty indices, either RAI or mFI-5, to predict 30-day mortality and non-home discharge. Predictive accuracy was characterized by area under the receiver operating characteristic curve (AUC-ROC), integrated calibration index (ICI), and continuous net reclassification index (NRI). RESULTS: 1786 patients (58.6%) died in the study cohort within 30 days, and 38.6% of eligible patients experienced non-home discharge. The baseline model showed good discrimination (AUC-ROC 0.77 for 30-day mortality and 0.74 for non-home discharge). AUC-ROC and ICI did not significantly change after adding frailty for 30-day mortality or non-home discharge. Adding RAI significantly improved NRI for 30-day mortality and non-home discharge; however, the magnitude was small and difficult to interpret, given other results including false positive and negative rates showing no difference in predictive accuracy. CONCLUSIONS: Incorporating frailty did not significantly improve predictive accuracy of models for 30-day mortality and non-home discharge following perioperative resuscitation. Thus, demonstrated associations between frailty and outcomes of perioperative resuscitation may not translate into improved predictive accuracy. When engaging patients in shared decision-making regarding do-not-resuscitate orders perioperatively, providers should acknowledge uncertainty in anticipating resuscitation outcomes.


Asunto(s)
Fragilidad , Paro Cardíaco , Humanos , Masculino , Femenino , Anciano , Estudios Retrospectivos , Fragilidad/complicaciones , Fragilidad/diagnóstico , Persona de Mediana Edad , Paro Cardíaco/mortalidad , Paro Cardíaco/terapia , Medición de Riesgo/métodos , Alta del Paciente/estadística & datos numéricos , Periodo Perioperatorio , Curva ROC , Anciano de 80 o más Años , Reanimación Cardiopulmonar/métodos
9.
Dalton Trans ; 53(20): 8657-8661, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38695748

RESUMEN

We describe a study of the influence of cryptand denticity on the structural, electronic, and electrochemical properties of UIII-containing cryptates. Two cryptands (2.2.2 and 2.2.1) are reported. The cryptand with the smaller denticity leads to negative electrochemical potentials and shorter bond lengths that are consistent with a better fit for UIII than the larger cryptand. These studies provide insight into the rational design of cryptand-based ligands for trivalent uranium.

10.
Bone Rep ; 21: 101774, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38778834

RESUMEN

As international incidence of diabetes and diabetes-driven comorbidities such as chronic kidney disease (CKD) continue to climb, interventions are needed that address the high-risk skeletal fragility of what is a complex disease state. Romosozumab (Romo) is an FDA-approved sclerostin inhibitor that has been shown to increase bone mineral density and decrease fracture rates in osteoporotic patients with mild to severe CKD, but its effect on diabetes-weakened bone is unknown. We aimed to test Romo's performance in a model of combined diabetes and CKD. 6-week old male C57BL/6 mice were randomly divided into control (CON) and disease model (STZ-Ad) groups, using a previously established streptozotocin- and adenine-diet-induced model. After 16 weeks of disease induction, both CON and STZ-Ad groups were subdivided into two treatment groups and given weekly subcutaneous injections of 100 µL vehicle (phosphorus buffered saline, PBS) or 10 mg/kg Romo. Mice were euthanized after 4 weeks of treatment via cardiac exsanguination and cervical dislocation. Hindlimb bones and L4 vertebrae were cleaned of soft tissue, wrapped in PBS-soaked gauze and stored at -20C. Right tibiae, femora, and L4s were scanned via microcomputed tomography; tibiae were then tested to failure in 4-pt bending while L4s were compression tested. Romo treatment significantly increased cortical and trabecular bone mass in both STZ-Ad and CON animals. These morphological improvements created corresponding increases in cortical bending strength and trabecular compression strength, with STZ-Ad treated mice surpassing vehicle CON mice in all trabecular mechanics measures. These results suggest that Romo retains its efficacy at increasing bone mass and strength in diabetic kidney disease.

11.
Vet Sci ; 11(5)2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38787185

RESUMEN

Locoregional anaesthetic techniques are invaluable for providing multimodal analgesia for painful surgical procedures. This prospective, randomised study describes a nerve stimulator-guided brachial plexus blockade (BPB) in rabbits undergoing orthopaedic surgery in comparison to systemic lidocaine. Premedication was provided with intramuscular (IM) medetomidine, fentanyl, and midazolam. Anaesthesia was induced (propofol IV) and maintained with isoflurane. Nine rabbits received a lidocaine BPB (2%; 0.3 mL kg-1), and eight received a lidocaine constant rate infusion (CRI) (2 mg kg-1 IV, followed by 100 µg kg-1 min-1). Rescue analgesia was provided with fentanyl IV. Carprofen was administered at the end of the surgery. Postoperative pain was determined using the Rabbit Grimace Scale (RGS) and a composite pain scale. Buprenorphine was administered according to the pain score for two hours after extubation. Rabbits were filmed during the first two hours to measure distance travelled and behaviours. Food intake and faeces output were compared. Every rabbit in CRI required intraoperative rescue analgesia compared to none in BPB. However, rabbits in both groups had similar pain scores, and there was no difference in the administration of postoperative analgesia. There were no significant differences in food intake or faeces production over 18 h, and no significant differences in distance travelled or behaviours examined during the first two hours. BPB seems superior for intraoperative analgesia. Postoperatively, both groups were comparable.

13.
Bone ; 183: 117089, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38575047

RESUMEN

INTRODUCTION: Patients with chronic kidney disease (CKD) are at an alarming risk of fracture compared to age and sex-matched non-CKD individuals. Clinical and preclinical data highlight two key factors in CKD-induced skeletal fragility: cortical porosity and reduced matrix-level properties including bone hydration. Thus, strategies are needed to address these concerns to improve mechanical properties and ultimately lower fracture risk in CKD. We sought to evaluate the singular and combined effects of mechanical and pharmacological interventions on modulating porosity, bone hydration, and mechanical properties in CKD. METHODS: Sixteen-week-old male C57BL/6J mice underwent a 10-week CKD induction period via a 0.2 % adenine-laced casein-based diet (n = 48) or remained as non-CKD littermate controls (Con, n = 48). Following disease induction (26 weeks of age), n = 7 CKD and n = 7 Con were sacrificed (baseline cohort) to confirm a steady-state CKD state was achieved prior to the initiation of treatment. At 27 weeks of age, all remaining mice underwent right tibial loading to a maximum tensile strain of 2050 µÆ 3× a week for five weeks with the contralateral limb as a non-loaded control. Half of the mice (equal number CKD and Con) received subcutaneous injections of 0.5 mg/kg raloxifene (RAL) 5× a week, and the other half remained untreated (UN). Mice were sacrificed at 31 weeks of age. Serum biochemistries were performed, and bi-lateral tibiae were assessed for microarchitecture, whole bone and tissue level mechanical properties, and composition including bone hydration. RESULTS: Regardless of intervention, BUN and PTH were higher in CKD animals throughout the study. In CKD, the combined effects of loading and RAL were quantified as lower cortical porosity and improved mechanical, material, and compositional properties, including higher matrix-bound water. Loading was generally responsible for positive impacts in cortical geometry and structural mechanical properties, while RAL treatment improved some trabecular outcomes and material-level mechanical properties and was responsible for improvements in several compositional parameters. While control animals responded positively to loading, their bones were less impacted by the RAL treatment, showing no deformation, toughness, or bound water improvements which were all evident in CKD. Serum PTH levels were negatively correlated with matrix-bound water. DISCUSSION: An effective treatment program to improve fracture risk in CKD ideally focuses on the cortical bone and considers both cortical porosity and matrix properties. Loading-induced bone formation and mechanical improvements were observed across groups, and in the CKD cohort, this included lower cortical porosity. This study highlights that RAL treatment superimposed on active bone formation may be ideal for reducing skeletal complications in CKD by forming new bone with enhanced matrix properties.


Asunto(s)
Fracturas Óseas , Insuficiencia Renal Crónica , Ratones , Humanos , Masculino , Animales , Clorhidrato de Raloxifeno/farmacología , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Fracturas Óseas/complicaciones , Agua
14.
Bone ; 185: 117111, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38679220

RESUMEN

Chronic heavy alcohol consumption is a risk factor for low trauma bone fracture. Using a non-human primate model of voluntary alcohol consumption, we investigated the effects of 6 months of ethanol intake on cortical bone in cynomolgus macaques (Macaca fascicularis). Young adult (6.4 ± 0.1 years old, mean ± SE) male cynomolgus macaques (n = 17) were subjected to a 4-month graded ethanol induction period, followed by voluntary self-administration of water or ethanol (4 % w/v) for 22 h/d, 7 d/wk. for 6 months. Control animals (n = 6) consumed an isocaloric maltose-dextrin solution. Tibial response was evaluated using densitometry, microcomputed tomography, histomorphometry, biomechanical testing, and Raman spectroscopy. Global bone response was evaluated using biochemical markers of bone turnover. Monkeys in the ethanol group consumed an average of 2.3 ± 0.2 g/kg/d ethanol resulting in a blood ethanol concentration of 90 ± 12 mg/dl in longitudinal samples taken 7 h after the daily session began. Ethanol consumption had no effect on tibia length, mass, density, mechanical properties, or mineralization (p > 0.642). However, compared to controls, ethanol intake resulted in a dose-dependent reduction in intracortical bone porosity (Spearman rank correlation = -0.770; p < 0.0001) and compared to baseline, a strong tendency (p = 0.058) for lower plasma CTX, a biochemical marker of global bone resorption. These findings are important because suppressed cortical bone remodeling can result in a decrease in bone quality. In conclusion, intracortical bone porosity was reduced to subnormal values 6 months following initiation of voluntary ethanol consumption but other measures of tibia architecture, mineralization, or mechanics were not altered.


Asunto(s)
Consumo de Bebidas Alcohólicas , Calcificación Fisiológica , Hueso Cortical , Macaca fascicularis , Animales , Masculino , Porosidad , Consumo de Bebidas Alcohólicas/fisiopatología , Hueso Cortical/efectos de los fármacos , Hueso Cortical/patología , Hueso Cortical/diagnóstico por imagen , Calcificación Fisiológica/efectos de los fármacos , Fenómenos Biomecánicos/efectos de los fármacos , Microtomografía por Rayos X , Tibia/efectos de los fármacos , Tibia/diagnóstico por imagen , Tibia/patología , Etanol/farmacología , Espectrometría Raman , Densidad Ósea/efectos de los fármacos
15.
Bone Rep ; 21: 101761, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38646090

RESUMEN

Spinal cord injury (SCI) leads to significant sublesional bone loss and high fracture rates. While loss of mechanical loading plays a significant role in SCI-induced bone loss, animal studies have demonstrated mechanical loading alone does not fully account for loss of bone following SCI. Indeed, we have shown that bone loss occurs below the level of an incomplete moderate contusion SCI, despite the resumption of weight-bearing and stepping. As systemic factors could also impact bone after SCI, bone alterations may also be present in bone sites above the level of injury. To examine this, we assessed bone microarchitecture and bone turnover in the supralesional humerus in male and female rats at two different ages following a moderate contusion injury in both sub-chronic (30 days) and chronic (180 days) time points after injury. At the 30-day timepoint, we found that both young and adult male SCI rats had decrements in trabecular bone volume at the supralesional proximal humerus (PH), while female SCI rats were not different from age-matched shams. At the 180-day timepoint, there were no statistical differences between SCI and sham groups, irrespective of age or sex, at the supralesional proximal humerus. At the 30-day timepoint, all SCI rats had lower BFR and higher osteoclast-covered trabecular surfaces in the proximal humerus compared to age-matched sham groups generally matching the pattern of SCI-induced changes in bone turnover seen in the sublesional proximal tibia. However, at the 180-day timepoint, only male SCI rats had lower BFR at the supralesional proximal humerus while female SCI rats had higher or no different BFR than their age-matched counterparts. Overall, this preclinical study demonstrates that a moderate contusion SCI leads to alterations in bone turnover above the level of injury within 30-days of injury; however male SCI rats maintained lower BFR in the supralesional humerus into long-term recovery. These data further highlight that bone loss after SCI is not driven solely by disuse. Additionally, these data allude to potential systemic factors exerting influence on bone following SCI and highlight the need to consider treatments for SCI-induced bone loss that impact both sublesional and systemic factors.

16.
JBMR Plus ; 8(2): ziae004, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38505524

RESUMEN

Skeletal fragility and high fracture rates are common in CKD. A key component of bone loss in CKD with secondary hyperparathyroidism is high bone turnover and cortical bone deterioration through both cortical porosity and cortical thinning. We hypothesized that RANKL drives high bone resorption within cortical bone leading to the development of cortical porosity in CKD (study 1) and that systemic inhibition of RANKL would mitigate the skeletal phenotype of CKD (study 2). In study 1, we assessed the skeletal properties of male and female Dmp1-cre RANKLfl/fl (cKO) and control genotype (Ranklfl/fl; Con) mice after 10 wk of adenine-induced CKD (AD; 0.2% dietary adenine). All AD mice regardless of sex or genotype had elevated blood urea nitrogen and high PTH. Con AD mice in both sexes had cortical porosity and lower cortical thickness as well as high osteoclast-covered trabecular surfaces and higher bone formation rate. cKO mice had preserved cortical bone microarchitecture despite high circulating PTH as well as no CKD-induced increases in osteoclasts. In study 2, male mice with established AD CKD were either given a single injection of an anti-RANKL antibody (5 mg/kg) 8 wk post-induction of CKD or subjected to 3×/wk dosing with risedronate (1.2 µg/kg) for 4 wk. Anti-RANKL treatment significantly reduced bone formation rate as well as osteoclast surfaces at both trabecular and cortical pore surfaces; risedronate treatment had little effect on these bone parameters. In conclusion, these studies demonstrate that bone-specific RANKL is critical for the development of high bone formation/high osteoclasts and cortical bone loss in CKD with high PTH. Additionally, systemic anti-RANKL ligand therapy in established CKD may help prevent the propagation of cortical bone loss via suppression of bone turnover.

17.
Am J Nephrol ; 55(3): 369-379, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38377965

RESUMEN

INTRODUCTION: Chronic kidney disease (CKD) negatively affects musculoskeletal health, leading to reduced mobility, and quality of life. In healthy populations, carnitine supplementation and aerobic exercise have been reported to improve musculoskeletal health. However, there are inconclusive results regarding their effectiveness and safety in CKD. We hypothesized that carnitine supplementation and individualized treadmill exercise would improve musculoskeletal health in CKD. METHODS: We used a spontaneously progressive CKD rat model (Cy/+ rat) (n = 11-12/gr): (1) Cy/+ (CKD-Ctrl), (2) CKD-carnitine (CKD-Carn), and (3) CKD-treadmill (CKD-TM). Carnitine (250 mg/kg) was injected daily for 10 weeks. Rats in the treadmill group ran 4 days/week on a 5° incline for 10 weeks progressing from 30 min/day for week one to 40 min/day for week two to 50 min/day for the remaining 8 weeks. At 32 weeks of age, we assessed overall cardiopulmonary fitness, muscle function, bone histology and architecture, and kidney function. Data were analyzed by one-way ANOVA with Tukey's multiple comparisons tests. RESULTS: Moderate to severe CKD was confirmed by biochemistries for blood urea nitrogen (mean 43 ± 5 mg/dL CKD-Ctrl), phosphorus (mean 8 ± 1 mg/dL CKD-Ctrl), parathyroid hormone (PTH; mean 625 ± 185 pg/mL CKD-Ctrl), and serum creatinine (mean 1.1 ± 0.2 mg/mL CKD-Ctrl). Carnitine worsened phosphorous (mean 11 ± 3 mg/dL CKD-Carn; p < 0.0001), PTH (mean 1,738 ± 1,233 pg/mL CKD-Carn; p < 0.0001), creatinine (mean 1 ± 0.3 mg/dL CKD-Carn; p < 0.0001), cortical bone thickness (mean 0.5 ± 0.1 mm CKD-Ctrl, 0.4 ± 0.1 mm CKD-Carn; p < 0.05). Treadmill running significantly improves maximal aerobic capacity when compared to CKD-Ctrl (mean 14 ± 2 min CKD-TM, 10 ± 2 min CKD-Ctrl; p < 0.01). CONCLUSION: Carnitine supplementation worsened CKD progression, mineral metabolism biochemistries, and cortical porosity and did not have an impact on physical function. Individualized treadmill running improved maximal aerobic capacity but did not have an impact on CKD progression or bone properties. Future studies should seek to better understand carnitine doses in conditions of compromised renal function to prevent toxicity which may result from elevated carnitine levels and to optimize exercise prescriptions for musculoskeletal health.


Asunto(s)
Carnitina , Suplementos Dietéticos , Condicionamiento Físico Animal , Insuficiencia Renal Crónica , Carnitina/administración & dosificación , Animales , Insuficiencia Renal Crónica/terapia , Insuficiencia Renal Crónica/sangre , Ratas , Masculino , Hormona Paratiroidea/sangre , Modelos Animales de Enfermedad , Músculo Esquelético/efectos de los fármacos , Capacidad Cardiovascular , Fósforo/sangre , Creatinina/sangre
18.
Bone ; 181: 117031, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38311304

RESUMEN

INTRODUCTION: Conventional bone imaging methods primarily use X-ray techniques to assess bone mineral density (BMD), focusing exclusively on the mineral phase. This approach lacks information about the organic phase and bone water content, resulting in an incomplete evaluation of bone health. Recent research highlights the potential of ultrashort echo time magnetic resonance imaging (UTE MRI) to measure cortical porosity and estimate BMD based on signal intensity. UTE MRI also provides insights into bone water distribution and matrix organization, enabling a comprehensive bone assessment with a single imaging technique. Our study aimed to establish quantifiable UTE MRI-based biomarkers at clinical field strength to estimate BMD and microarchitecture while quantifying bound water content and matrix organization. METHODS: Femoral bones from 11 cadaveric specimens (n = 4 males 67-92 yrs of age, n = 7 females 70-95 yrs of age) underwent dual-echo UTE MRI (3.0 T, 0.45 mm resolution) with different echo times and high resolution peripheral quantitative computed tomography (HR-pQCT) imaging (60.7 µm voxel size). Following registration, a 4.5 mm HR-pQCT region of interest was divided into four quadrants and used across the multi-modal images. Statistical analysis involved Pearson correlation between UTE MRI porosity index and a signal-intensity technique used to estimate BMD with corresponding HR-pQCT measures. UTE MRI was used to calculate T1 relaxation time and a novel bound water index (BWI), compared across subregions using repeated measures ANOVA. RESULTS: The UTE MRI-derived porosity index and signal-intensity-based estimated BMD correlated with the HR-pQCT variables (porosity: r = 0.73, p = 0.006; BMD: r = 0.79, p = 0.002). However, these correlations varied in strength when we examined each of the four quadrants (subregions, r = 0.11-0.71). T1 relaxometry and the BWI exhibited variations across the four subregions, though these differences were not statistically significant. Notably, we observed a strong negative correlation between T1 relaxation time and the BWI (r = -0.87, p = 0.0006). CONCLUSION: UTE MRI shows promise for being an innocuous method for estimating cortical porosity and BMD parameters while also giving insight into bone hydration and matrix organization. This method offers the potential to equip clinicians with a more comprehensive array of imaging biomarkers to assess bone health without the need for invasive or ionizing procedures.


Asunto(s)
Hueso Cortical , Imagen por Resonancia Magnética , Masculino , Femenino , Humanos , Niño , Estudios de Factibilidad , Microtomografía por Rayos X , Hueso Cortical/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Agua
19.
Ann Surg ; 2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-38258581

RESUMEN

OBJECTIVE: To characterize the perceptions of surgeons, anesthesiologists, and geriatricians regarding perioperative CPR in surgical patients with frailty. SUMMARY BACKGROUND DATA: The population of patients undergoing surgery is growing older and more frail. Despite a growing focus on goal-concordant care, frailty assessment, and debate regarding the appropriateness of cardiopulmonary resuscitation (CPR) in patients with frailty, providers' views regarding frailty and perioperative CPR are unknown. METHODS: We performed qualitative thematic analysis of transcripts from semi-structured interviews of anesthesiologists (8), surgeons (10), and geriatricians (9) who care for high-risk surgical patients at two academic medical centers in Boston, MA. The interview guide elicited clinicians' understanding of frailty, approach to decision-making regarding perioperative CPR, and perceptions of perioperative CPR in frail surgical patients. RESULTS: We identified 5 themes: perceptions of perioperative CPR in patients with frailty vary by provider specialty; judgments regarding appropriateness of CPR in surgical patients with frailty are typically multifactorial and include patient goals, age, comorbidities, and arrest etiology; resuscitation in patients with frailty is sometimes associated with moral distress; biases such as ableism and ageism may skew clinicians' perceptions of appropriateness of perioperative CPR in patients with frailty; and evidence to guide risk stratification for patients with frailty undergoing perioperative CPR is inadequate. CONCLUSIONS: Anesthesiologists, surgeons, and geriatricians offer different accounts of frailty's relevance to judgments regarding CPR in surgical patients. Divergent views regarding frailty and perioperative CPR may impede efforts to deliver goal-concordant care and suggest a need for research to inform risk stratification, predict patient-centered outcomes, and understand the role of potential biases such as ageism and ableism.

20.
BMC Prim Care ; 25(1): 42, 2024 01 27.
Artículo en Inglés | MEDLINE | ID: mdl-38281026

RESUMEN

BACKGROUND: Artificial intelligence (AI) is a rapidly advancing field that is beginning to enter the practice of medicine. Primary care is a cornerstone of medicine and deals with challenges such as physician shortage and burnout which impact patient care. AI and its application via digital health is increasingly presented as a possible solution. However, there is a scarcity of research focusing on primary care physician (PCP) attitudes toward AI. This study examines PCP views on AI in primary care. We explore its potential impact on topics pertinent to primary care such as the doctor-patient relationship and clinical workflow. By doing so, we aim to inform primary care stakeholders to encourage successful, equitable uptake of future AI tools. Our study is the first to our knowledge to explore PCP attitudes using specific primary care AI use cases rather than discussing AI in medicine in general terms. METHODS: From June to August 2023, we conducted a survey among 47 primary care physicians affiliated with a large academic health system in Southern California. The survey quantified attitudes toward AI in general as well as concerning two specific AI use cases. Additionally, we conducted interviews with 15 survey respondents. RESULTS: Our findings suggest that PCPs have largely positive views of AI. However, attitudes often hinged on the context of adoption. While some concerns reported by PCPs regarding AI in primary care focused on technology (accuracy, safety, bias), many focused on people-and-process factors (workflow, equity, reimbursement, doctor-patient relationship). CONCLUSION: Our study offers nuanced insights into PCP attitudes towards AI in primary care and highlights the need for primary care stakeholder alignment on key issues raised by PCPs. AI initiatives that fail to address both the technological and people-and-process concerns raised by PCPs may struggle to make an impact.


Asunto(s)
Relaciones Médico-Paciente , Médicos , Humanos , Inteligencia Artificial , Impulso (Psicología) , Atención Primaria de Salud
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