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1.
Clin Infect Dis ; 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38606799

RESUMEN

Body weight is influenced by an interplay of individual and environmental factors. In people with HIV (PWH), weight is also influenced by disease status with loss accompanying disease progression that is reversed with effective antiretroviral therapy (ART). Weight changes in comparative ART trials differ by regimen, with greater gains observed with the integrase strand transfer inhibitors (INSTIs) dolutegravir and bictegravir, particularly when co-administered with tenofovir alafenamide fumarate (TAF), compared to regimens that include agents such as tenofovir disoproxil fumarate (TDF) that attenuate weight gain. We review weight changes in major randomized trials of pre-exposure prophylaxis (PrEP) and initial and switch HIV therapy, highlighting the challenges to assessing the role of ART in weight change. This examination forms the basis for a model that questions assumptions regarding an association between INSTI and TAF and excessive weight gain and calls for more careful consideration of these data when making HIV treatment decisions.

2.
J Strength Cond Res ; 38(5): 906-911, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38241463

RESUMEN

ABSTRACT: Cohen, JL, Cade, WH, Harrah, TC, Costello II, JP, and Kaplan, LD. The surgical management of NCAA Division 1 college football injuries post COVID-19: A single institution retrospective review. J Strength Cond Res 38(5): 906-911, 2024-The unprecedented COVID-19 pandemic had a significant impact on college football operations, including athletes' training regimens. As a result of these changes, concern for increased injury susceptibility post COVID-19 regulations has become a point of discussion. The current study sought to evaluate the incidence of surgical injury among NCAA Division 1 college football players at the authors' institution during the first full season after start of the COVID-19 pandemic compared with previous years. Retrospective chart review was performed for all players who sustained injuries requiring surgery while a member of the NCAA Division 1 football program during the 2009-2021 seasons. A p -value of ≤0.05 was used to determine significance. A total of 23 surgical injuries occurred in 22 players during the 2021 season compared with 121 in 118 players in the 12 previous seasons combined ( p = 0.0178; RR = 1.47). There was a significant increase in shoulder injuries ( n = 13 vs. n = 31; p = <0.0001; RR = 3.05) and specifically a significant increase in labral tears ( n = 10 vs. n = 30; p = 0.0003; RR = 2.74). No difference was seen in knee injuries ( n = 10 vs. n = 77; p = 0.27; RR = 1.35) and specifically no difference in anterior cruciate ligament injuries ( n = 3 vs. n = 31; p = 0.77; RR = 1.17). This phenomenon is multifactorial in nature, but alterations to players' training and preparations because of the COVID-19 pandemic likely resulted in suboptimal conditioning, leading to the increased incidence of surgical injuries emphasizing the importance of adequate strength training and conditioning.


Asunto(s)
Traumatismos en Atletas , COVID-19 , Fútbol Americano , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Estudios Retrospectivos , Fútbol Americano/lesiones , Masculino , Traumatismos en Atletas/epidemiología , Traumatismos en Atletas/cirugía , Universidades , Lesiones del Hombro/epidemiología , Incidencia , Adulto Joven , SARS-CoV-2 , Traumatismos de la Rodilla/cirugía , Traumatismos de la Rodilla/epidemiología , Lesiones del Ligamento Cruzado Anterior/cirugía , Lesiones del Ligamento Cruzado Anterior/epidemiología
3.
Obes Surg ; 34(1): 30-42, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37999891

RESUMEN

INTRODUCTION: This survey of international experts in obesity management was conducted to achieve consensus on standardized definitions and to identify areas of consensus and non-consensus in metabolic bariatric surgery (MBS) to assist in an algorithm of clinical practice guidelines for the management of obesity. METHODS: A three-round Delphi survey with 136 statements was conducted by 43 experts in obesity management comprising 26 bariatric surgeons, 4 endoscopists, 8 endocrinologists, 2 nutritionists, 2 counsellors, an internist, and a pediatrician spanning six continents over a 2-day meeting in Hamburg, Germany. To reduce bias, voting was unanimous, and the statements were neither favorable nor unfavorable to the issue voted or evenly balanced between favorable and unfavorable. Consensus was defined as ≥ 70% inter-voter agreement. RESULTS: Consensus was reached on all 15 essential definitional and reporting statements, including initial suboptimal clinical response, baseline weight, recurrent weight gain, conversion, and revision surgery. Consensus was reached on 95/121 statements on the type of surgical procedures favoring Roux-en-Y gastric bypass, sleeve gastrectomy, and endoscopic sleeve gastroplasty. Moderate consensus was reached for sleeve gastrectomy single-anastomosis duodenoileostomy and none on the role of intra-gastric balloons. Consensus was reached for MBS in patients > 65 and < 18 years old, with a BMI > 50 kg/m2, and with various obesity-related complications such as type 2 diabetes, liver, and kidney disease. CONCLUSIONS: In this survey of 43 multi-disciplinary experts, consensus was reached on standardized definitions and reporting standards applicable to the whole medical community. An algorithm for treating patients with obesity was explored utilizing a thoughtful multimodal approach.


Asunto(s)
Manejo de la Obesidad , Obesidad Mórbida , Adolescente , Anciano , Humanos , Cirugía Bariátrica/métodos , Consenso , Técnica Delphi , Diabetes Mellitus Tipo 2/cirugía , Gastrectomía/métodos , Derivación Gástrica/métodos , Obesidad/cirugía , Obesidad Mórbida/cirugía , Guías de Práctica Clínica como Asunto
4.
J Strength Cond Res ; 38(1): 97-104, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-37844189

RESUMEN

ABSTRACT: Costello II, JP, Wagner, JD, Dahl, VA, Cohen, JL, Reuter, AM, and Kaplan, LD. Effects of COVID-19 on rate of injury and position-specific injury during the 2020 National Football League season. J Strength Cond Res 38(1): 97-104, 2024-Because of the COVID-19 pandemic, the National Football League (NFL) made changes to its operations for the 2020 season. We hypothesize an increase in the rate of injuries during the 2020 season. Publicly available data were reviewed to identify NFL injuries from the 2015-2020 seasons. Player position, description of injury, date of injury, and injury setting were recorded. p ≤ 0.05 was considered statistically significant. For the 2020 season, compared with the 2015-2019 seasons, there was an increased risk of injury during the regular season overall relative risk (RR) = 1.308 ( p < 0.05), week (W)1 RR = 7.33 ( p < 0.05), W1-6 RR = 1.964 ( p < 0.05), W7-12 RR = 1.8909 ( p < 0.05), and during the postseason overall RR = 1.1444 ( p < 0.05), calculated using analysis of variance. There was an overall increased risk of abdominal or core injuries RR = 1.248 ( p < 0.05), groin or hip injuries RR = 2.534 ( p < 0.05), and hamstring injuries RR = 3.644 ( p < 0.05). There was an increased risk of hamstring injuries in cornerbacks RR = 3.219 ( p < 0.05) and running backs RR = 1.1394 ( p < 0.05), hip or groin injuries in guards RR = 1.105 ( p < 0.05), Achilles tendon injuries in safeties RR = 1.6976 ( p < 0.05), quadriceps injuries in running backs RR = 1.6191 ( p < 0.05), and arm injuries in defensive tackles RR = 1.221 ( p < 0.05). There was an increase in the overall rate of injuries in the 2020 NFL season, both in the regular season and postseason, compared with the 2015-2019 seasons. The overall rate of abdominal or core, groin or hip, and hamstring injuries increased. Specific player positions saw unique increases in rates of injuries. These findings may be due to numerous operational changes implemented, such as reduced in-person training and the elimination of the preseason, leading to suboptimal, sports-specific conditioning and increased risk of musculoskeletal injury.


Asunto(s)
COVID-19 , Fútbol Americano , Traumatismos de los Tejidos Blandos , Humanos , Fútbol Americano/lesiones , Estaciones del Año , Pandemias , COVID-19/epidemiología , Músculos Abdominales
5.
Artículo en Inglés | MEDLINE | ID: mdl-38054747

RESUMEN

An 18-year-old collegiate baseball player sustained an acute batter's shoulder injury causing a posterior shoulder dislocation with type IX 360° superior labrum from anterior to posterior tear. To the authors' knowledge, this description of batter's shoulder is not within the literature. The patient ultimately underwent arthroscopic labral repair and has fully returned to sport. In understanding the complexity of the shoulder during the batter's swing, this case demonstrates an expansion to the previously described pathophysiology of batter's shoulder.


Asunto(s)
Béisbol , Luxación del Hombro , Articulación del Hombro , Humanos , Adolescente , Hombro/cirugía , Béisbol/lesiones , Béisbol/fisiología , Articulación del Hombro/cirugía , Artroscopía/efectos adversos , Luxación del Hombro/cirugía , Luxación del Hombro/etiología
7.
Gastroenterol Clin North Am ; 52(4): xi-xii, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37919027
8.
Orthop J Sports Med ; 11(10): 23259671231201832, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37846315

RESUMEN

Background: Both partial- and full-thickness quadriceps tendon (QT) graft harvests are used for anterior cruciate ligament reconstruction (ACLR). Purpose: To evaluate the impact of QT graft harvest depth (full or partial thickness) on electromechanical delay (EMD), peak torque (PT), and rate of torque development (RTD) after ACLR. Study Design: Controlled laboratory study. Methods: A total of 26 patients who underwent either partial-thickness (n = 14) or full-thickness (n = 12) autograft QT ACLR were recruited between June and November 2021 (>1 year before participation). Patients performed isokinetic knee extension testing with surface electromyography of the quadriceps muscles. Mixed repeated-measures analysis of variance with least significant difference post hoc testing was used to determine significant differences (mean difference [MD] ± SE) or interactions for all variables. Results: A significant speed×depth interaction was seen for the vastus medialis (P = .005). Pairwise analyses showed significantly longer EMD for the partial-thickness graft than the full-thickness graft (MD ± SE, 19.92 ± 6.33 ms; P = .006). In the partial-thickness graft, the EMD was significantly longer at 90 deg/s versus 180 deg/s (MD ± SE, 19.11 ± 3.95 ms; P < .001) and 300 deg/s (MD ± SE, 16.43 ± 5.30 ms; P = .006). For PT, the full-thickness graft had a significantly lower PT on the operated versus nonoperated side at all speeds (MD ± SE: 90 deg/s, -57.0 ± 10.5 N·m, P < .001; 180 deg/s, -26.0 ± 10.2 N·m, P = .020; 300 deg/s, -20.3 ± 8.9 N·m, P = .034). For RTD, the full-thickness graft showed significantly Slower RTD for the operated versus nonoperated side at all time points (MD ± SD: RTD0-25 (0-25% of the range of motion), -131.3 ± 50.9 N·m/s, P = .018; RTD25-50, -197.0 ± 72.5 N·m/s, P = .014; RTD50-75, -113.3 ± 39.8 N·m/s, P = .013; RTD75-100, -149.4 ± 35.9 N·m/s, P < .001). Conclusion: Compared with partial-thickness QT, full-thickness QT showed a shorter vastus medialis EMD at higher loading, and therefore greater stiffness, as well as slower RTD and lower PT across all testing speeds. Clinical Relevance: The impact of full-thickness QT autograft on EMD and neuromuscular performance should be considered for ACLR.

9.
Bioengineering (Basel) ; 10(10)2023 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-37892870

RESUMEN

Diabetic foot ulcer (DFU) is associated with neuropathy and/or peripheral artery disease of the lower limb in diabetic patients, affecting quality of life and leading to repeated hospitalizations and infections [...].

11.
Cureus ; 15(10): e46898, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37841980

RESUMEN

Background Due to the COVID-19 pandemic, many professional sports leagues such as the National Hockey League (NHL) made significant changes to their schedules and operating procedures. Changes included a modified 2019-2020 playoff format, the removal of the 2020-2021 preseason, and condensed game schedules. Though these modifications were made in an effort to protect players from COVID-19, they resulted in decreased training time and preparation. The purpose of this study was to assess the impact of these changes on the rate of player injuries in the NHL both after the resumption of the midseason stoppage and during the subsequent seasons. Hypothesis/purpose Changes to the NHL schedule amid the COVID-19 pandemic resulted in a significant increase in player injury rates. Methods NHL injuries were obtained from an NHL injury database for the 2018-2019 through the 2021-2022 seasons. The date of injury, date of return, injury description, player age, and player position were recorded. Injury rates were calculated as the number of total athlete injuries per 1000 game exposures (GEs). The primary outcome was the injury proportion ratio (IPR) when comparing the injury rates of the post-COVID-19 season with baseline seasons. Secondary measures analyzed injuries based on age, anatomic location, month in the season, position, length of injury, season-ending injuries, and recurring injuries. Results A total of 4604 injuries were recorded between 2018 and 2022. The modified 2019-2020 playoffs had significantly higher rates of injury (IPR = 1.84, 95% confidence interval {CI} = 1.36-2.49) with more game exposures per week. The 2020-2021 season had significantly higher rates of overall player injury compared to baseline seasons (IPR = 1.19, 95% CI = 1.09-1.30) and also had a higher rate of season-ending injuries (IPR = 1.71, 95% CI = 1.38-2.11). Most injuries occurred in the first few months of the 2020-2021 season. There was no significant difference in injury rate based on age group and no significant difference in the average length of injury between seasons. Conclusion Increases in injury rates could be due to decreased offseason training between seasons, the elimination of preseason games, and increased game density. Decreasing typical training timelines and eliminating the preseason to rapidly return to normal competition after unexpected events (pandemics, lockdowns, etc.) may pose a risk to player safety in the NHL. These findings should be considered before future schedule changes in professional hockey.

12.
bioRxiv ; 2023 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-37662374

RESUMEN

Knee osteoarthritis (KOA) is a degenerative disease resulting from mechanical overload, where direct physical impacts on chondrocytes play a crucial role in disease development by inducing inflammation and extracellular matrix degradation. However, the signaling cascades that sense these physical impacts and induce the pathogenic transcriptional programs of KOA remain to be defined, which hinders the identification of novel therapeutic approaches. Recent studies have implicated a crucial role of Hippo signaling in osteoarthritis. Since Hippo signaling senses mechanical cues, we aimed to determine its role in chondrocyte responses to mechanical overload. Here we show that mechanical loading induces the expression of inflammatory and matrix-degrading genes by activating the nuclear factor-kappaB (NFκB) pathway in a Hippo-dependent manner. Applying mechanical compressional force to 3-dimensional cultured chondrocytes activated NFκB and induced the expression of NFκB target genes for inflammation and matrix degradation (i.e., IL1ß and ADAMTS4). Interestingly, deleting the Hippo pathway effector YAP or activating YAP by deleting core Hippo kinases LATS1/2 blocked the NFκB pathway activation induced by mechanical loading. Consistently, treatment with a LATS1/2 kinase inhibitor abolished the upregulation of IL1ß and ADAMTS4 caused by mechanical loading. Mechanistically, mechanical loading activates Protein Kinase C (PKC), which activates NFκB p65 by phosphorylating its Serine 536. Furthermore, the mechano-activation of both PKC and NFκB p65 is blocked in LATS1/2 or YAP knockout cells, indicating that the Hippo pathway is required by this mechanoregulation. Additionally, the mechanical loading-induced phosphorylation of NFκB p65 at Ser536 is blocked by the LATS1/2 inhibitor Lats-In-1 or the PKC inhibitor AEB-071. Our study suggests that the interplay of the Hippo signaling and PKC controls NFκB-mediated inflammation and matrix degradation in response to mechanical loading. Chemical inhibitors targeting Hippo signaling or PKC can prevent the mechanoresponses of chondrocytes associated with inflammation and matrix degradation, providing a novel therapeutic strategy for KOA.

13.
JAMA Netw Open ; 6(8): e2329310, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37589975

RESUMEN

Importance: Both augmented reality (AR) and virtual reality (VR) have had increasing applications in medicine, including medical training, psychology, physical medicine, rehabilitation, and surgical specialties, such as neurosurgery and orthopedic surgery. There are little data on AR's effect on patients' anxiety and experiences. Objective: To determine whether the use of an AR walkthrough effects patient perioperative anxiety. Design, Setting, and Participants: This randomized clinical trial was conducted at an outpatient surgery center in 2021 to 2022. All patients undergoing elective orthopedic surgery with the senior author were randomized to the treatment or control group. Analyses were conducted per protocol. Data analysis was performed in November 2022. Intervention: AR experience explaining to patients what to expect on their day of surgery and walking them through the surgery space. The control group received the standard educational packet. Main Outcomes and Measures: The main outcome was change in State-Trait Anxiety Inventory (STAI) from the screening survey to the preoperative survey. Results: A total of 140 patients were eligible, and 45 patients either declined or were excluded. Therefore, 95 patients (63 [66.3%] male; mean [SD] age, 38 [16] years) were recruited for the study and included in the final analysis; 46 patients received the AR intervention, and 49 patients received standard instructions. The AR group experienced a decrease in anxiety from the screening to preoperative survey (mean score change, -2.4 [95% CI, -4.6 to -0.3]), while the standard care group experienced an increase (mean score change, 2.6 [95% CI, 0.2 to 4.9]; P = .01). All patients postoperatively experienced a mean decrease in anxiety score compared with both the screening survey (mean change: AR, -5.4 [95% CI, -7.9 to -2.9]; standard care, -6.9 [95% CI, -11.5 to -2.2]; P = .32) and preoperative survey (mean change: AR, -8.0 [95% CI, -10.3 to -5.7]; standard care, -4.2 [95% CI, -8.6 to 0.2]; P = .19). Of 42 patients in the AR group who completed the postoperative follow-up survey, 30 (71.4%) agreed or strongly agreed that they enjoyed the experience, 29 (69.0%) agreed or strongly agreed that they would recommend the experience, and 28 (66.7%) agreed or strongly agreed that they would use the experience again. No differences were observed in postoperative pain levels or narcotic use. Conclusions and Relevance: In this randomized clinical trial, the use of AR decreased preoperative anxiety compared with traditional perioperative education and handouts, but there was no significant effect on postoperative anxiety, pain levels, or narcotic use. These findings suggest that AR may serve as an effective means of decreasing preoperative patient anxiety. Trial Registration: ClinicalTrials.gov Identifier: NCT04727697.


Asunto(s)
Realidad Aumentada , Medicina , Humanos , Masculino , Adulto , Femenino , Ansiedad/prevención & control , Trastornos de Ansiedad , Narcóticos
14.
Cells ; 12(10)2023 05 18.
Artículo en Inglés | MEDLINE | ID: mdl-37408255

RESUMEN

Osteoarthritis (OA) is the most common cause of disability worldwide among the elderly. Alarmingly, the incidence of OA in individuals less than 40 years of age is rising, likely due to the increase in obesity and post-traumatic osteoarthritis (PTOA). In recent years, due to a better understanding of the underlying pathophysiology of OA, several potential therapeutic approaches targeting specific molecular pathways have been identified. In particular, the role of inflammation and the immune system has been increasingly recognized as important in a variety of musculoskeletal diseases, including OA. Similarly, higher levels of host cellular senescence, characterized by cessation of cell division and the secretion of a senescence-associated secretory phenotype (SASP) within the local tissue microenvironments, have also been linked to OA and its progression. New advances in the field, including stem cell therapies and senolytics, are emerging with the goal of slowing disease progression. Mesenchymal stem/stromal cells (MSCs) are a subset of multipotent adult stem cells that have demonstrated the potential to modulate unchecked inflammation, reverse fibrosis, attenuate pain, and potentially treat patients with OA. Numerous studies have demonstrated the potential of MSC extracellular vesicles (EVs) as cell-free treatments that comply with FDA regulations. EVs, including exosomes and microvesicles, are released by numerous cell types and are increasingly recognized as playing a critical role in cell-cell communication in age-related diseases, including OA. Treatment strategies for OA are being developed that target senescent cells and the paracrine and autocrine secretions of SASP. This article highlights the encouraging potential for MSC or MSC-derived products alone or in combination with senolytics to control patient symptoms and potentially mitigate the progression of OA. We will also explore the application of genomic principles to the study of OA and the potential for the discovery of OA phenotypes that can motivate more precise patient-driven treatments.


Asunto(s)
Vesículas Extracelulares , Células Madre Mesenquimatosas , Osteoartritis , Humanos , Senoterapéuticos , Vesículas Extracelulares/metabolismo , Osteoartritis/terapia , Osteoartritis/metabolismo , Inflamación/metabolismo , Células Madre Mesenquimatosas/metabolismo
15.
Cells ; 12(14)2023 07 11.
Artículo en Inglés | MEDLINE | ID: mdl-37508489

RESUMEN

The onset and progression of human inflammatory joint diseases are strongly associated with the activation of resident synovium/infrapatellar fat pad (IFP) pro-inflammatory and pain-transmitting signaling. We recently reported that intra-articularly injected IFP-derived mesenchymal stem/stromal cells (IFP-MSC) acquire a potent immunomodulatory phenotype and actively degrade substance P (SP) via neutral endopeptidase CD10 (neprilysin). Our hypothesis is that IFP-MSC robust immunomodulatory therapeutic effects are largely exerted via their CD10-bound small extracellular vesicles (IFP-MSC sEVs) by attenuating synoviocyte pro-inflammatory activation and articular cartilage degradation. Herein, IFP-MSC sEVs were isolated from CD10High- and CD10Low-expressing IFP-MSC cultures and their sEV miRNA cargo was assessed using multiplex methods. Functionally, we interrogated the effect of CD10High and CD10Low sEVs on stimulated by inflammatory/fibrotic cues synoviocyte monocultures and cocultures with IFP-MSC-derived chondropellets. Finally, CD10High sEVs were tested in vivo for their therapeutic capacity in an animal model of acute synovitis/fat pad fibrosis. Our results showed that CD10High and CD10Low sEVs possess distinct miRNA profiles. Reactome analysis of miRNAs highly present in sEVs showed their involvement in the regulation of six gene groups, particularly those involving the immune system. Stimulated synoviocytes exposed to IFP-MSC sEVs demonstrated significantly reduced proliferation and altered inflammation-related molecular profiles compared to control stimulated synoviocytes. Importantly, CD10High sEV treatment of stimulated chondropellets/synoviocyte cocultures indicated significant chondroprotective effects. Therapeutically, CD10High sEV treatment resulted in robust chondroprotective effects by retaining articular cartilage structure/composition and PRG4 (lubricin)-expressing cartilage cells in the animal model of acute synovitis/IFP fibrosis. Our study suggests that CD10High sEVs possess immunomodulatory miRNA attributes with strong chondroprotective/anabolic effects for articular cartilage in vivo. The results could serve as a foundation for sEV-based therapeutics for the resolution of detrimental aspects of immune-mediated inflammatory joint changes associated with conditions such as osteoarthritis (OA).


Asunto(s)
Cartílago Articular , Vesículas Extracelulares , MicroARNs , Osteoartritis , Sinovitis , Animales , Humanos , Sinovitis/metabolismo , Osteoartritis/metabolismo , Vesículas Extracelulares/metabolismo , Articulación de la Rodilla/metabolismo , MicroARNs/metabolismo , Cartílago Articular/metabolismo , Neprilisina/metabolismo , Fibrosis , Homeostasis , Células del Estroma/metabolismo
16.
N Engl J Med ; 389(6): 514-526, 2023 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-37366315

RESUMEN

BACKGROUND: Retatrutide (LY3437943) is an agonist of the glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, and glucagon receptors. Its dose-response relationships with respect to side effects, safety, and efficacy for the treatment of obesity are not known. METHODS: We conducted a phase 2, double-blind, randomized, placebo-controlled trial involving adults who had a body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) of 30 or higher or who had a BMI of 27 to less than 30 plus at least one weight-related condition. Participants were randomly assigned in a 2:1:1:1:1:2:2 ratio to receive subcutaneous retatrutide (1 mg, 4 mg [initial dose, 2 mg], 4 mg [initial dose, 4 mg], 8 mg [initial dose, 2 mg], 8 mg [initial dose, 4 mg], or 12 mg [initial dose, 2 mg]) or placebo once weekly for 48 weeks. The primary end point was the percentage change in body weight from baseline to 24 weeks. Secondary end points included the percentage change in body weight from baseline to 48 weeks and a weight reduction of 5% or more, 10% or more, or 15% or more. Safety was also assessed. RESULTS: We enrolled 338 adults, 51.8% of whom were men. The least-squares mean percentage change in body weight at 24 weeks in the retatrutide groups was -7.2% in the 1-mg group, -12.9% in the combined 4-mg group, -17.3% in the combined 8-mg group, and -17.5% in the 12-mg group, as compared with -1.6% in the placebo group. At 48 weeks, the least-squares mean percentage change in the retatrutide groups was -8.7% in the 1-mg group, -17.1% in the combined 4-mg group, -22.8% in the combined 8-mg group, and -24.2% in the 12-mg group, as compared with -2.1% in the placebo group. At 48 weeks, a weight reduction of 5% or more, 10% or more, and 15% or more had occurred in 92%, 75%, and 60%, respectively, of the participants who received 4 mg of retatrutide; 100%, 91%, and 75% of those who received 8 mg; 100%, 93%, and 83% of those who received 12 mg; and 27%, 9%, and 2% of those who received placebo. The most common adverse events in the retatrutide groups were gastrointestinal; these events were dose-related, were mostly mild to moderate in severity, and were partially mitigated with a lower starting dose (2 mg vs. 4 mg). Dose-dependent increases in heart rate peaked at 24 weeks and declined thereafter. CONCLUSIONS: In adults with obesity, retatrutide treatment for 48 weeks resulted in substantial reductions in body weight. (Funded by Eli Lilly; ClinicalTrials.gov number, NCT04881760.).


Asunto(s)
Fármacos Antiobesidad , Polipéptido Inhibidor Gástrico , Péptido 1 Similar al Glucagón , Obesidad , Receptores de Glucagón , Adulto , Femenino , Humanos , Masculino , Índice de Masa Corporal , Método Doble Ciego , Péptido 1 Similar al Glucagón/agonistas , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Resultado del Tratamiento , Pérdida de Peso/efectos de los fármacos , Polipéptido Inhibidor Gástrico/agonistas , Receptores de Glucagón/agonistas , Inyecciones Subcutáneas , Fármacos Antiobesidad/administración & dosificación , Fármacos Antiobesidad/efectos adversos , Fármacos Antiobesidad/farmacología , Fármacos Antiobesidad/uso terapéutico
17.
J Orthop ; 39: 50-58, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37125014

RESUMEN

Introduction: The clavicle is the most frequently fractured bone in the human body, and up to 80% of clavicle fractures occur in the middle third diaphyseal region of the clavicle (midshaft). We conducted a bibliometric analysis to identify and evaluate the 50 most-cited publications pertaining to midshaft clavicle fractures (MCF). Materials and methods: Two independent reviewers conducted separate queries on Web of Science in December 2021 for "midshaft clavicle fractures". The publications yielded were organized from highest to lowest number of citations. We included articles, review articles, and editorial materials and excluded other document types. Both reviewers independently reviewed all abstracts until 50 studies pertaining to MCF were included. Theory: We hypothesized that most articles would be published between 2000 and 2019, pertain to outcomes, and those with a greater (lower numeric) level of evidence would correlate with number of citations. Results: The most prolific decade was from 2010 to 2019, with 50% (25/50) of articles published. Average citation density was 6.3 ± 5.5 (range, 1.3-33.1), defined as the average number of citations per year since publication. The median level of evidence (LOE) was 3.5 (IQR: 3). One-way ANOVA tests were used to compare the effects of LOE on total citations and citation density. There were statistically significant differences in total citations (F value = 12.07, p = 0.001) and citation density (F value = 21.14, p < 0.001) between LOE groups. The median number of total citations, grouped by LOE of 1 through 5, were as follows: 110, 66, 66, 51, 52. Conclusions: This review provides an overview of the 50 most cited papers regarding MCF. This should be used as a reference for physicians and other providers who treat patients with MCF for treatment guidance and for those in teaching roles as a student and resident/fellow educational resource.

18.
Front Bioeng Biotechnol ; 11: 1040762, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36741745

RESUMEN

Tendinopathies encompass a highly prevalent, multi-faceted spectrum of disorders, characterized by activity-related pain, compromised function, and propensity for an extended absence from sport and the workplace. The pathophysiology of tendinopathy continues to evolve. For decades, it has been related primarily to repetitive overload trauma but more recently, the onset of tendinopathy has been attributed to the tissue's failed attempt to heal after subclinical inflammatory and immune challenges (failed healing model). Conventional tendinopathy management produces only short-term symptomatic relief and often results in incomplete repair or healing leading to compromised tendon function. For this reason, there has been increased effort to develop therapeutics to overcome the tissue's failed healing response by targeting the cellular metaplasia and pro-inflammatory extra-cellular environment. On this basis, stem cell-based therapies have been proposed as an alternative therapeutic approach designed to modify the course of the various tendon pathologies. Mesenchymal stem/stromal cells (MSCs) are multipotent stem cells often referred to as "medicinal signaling cells" due to their immunomodulatory and anti-inflammatory properties that can produce a pro-regenerative microenvironment in pathological tendons. However, the adoption of MSCs into clinical practice has been limited by FDA regulations and perceived risk of adverse events upon infusion in vivo. The introduction of cell-free approaches, such as the extracellular vesicles of MSCs, has encouraged new perspectives for the treatment of tendinopathies, showing promising short-term results. In this article, we review the most recent advances in MSC-based and MSC-derived therapies for tendinopathies. Preclinical and clinical studies are included with comment on future directions of this rapidly developing therapeutic modality, including the importance of understanding tissue loading and its relationship to any treatment regimen.

19.
Am J Sports Med ; 51(4): 942-948, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36790220

RESUMEN

BACKGROUND: Anterior cruciate ligament reconstruction (ACLR) using the quadriceps tendon is an increasingly popular technique. Both partial-thickness quadriceps tendon (PT-Q) and full-thickness quadriceps tendon (FT-Q) graft depths are employed. HYPOTHESIS/PURPOSE: This study was designed to assess isokinetic peak torque, average power, and total work during knee extension in patients with FT-Q or PT-Q grafts for ACLR. We hypothesized that both groups would show lower isokinetic values for the operated side, with greater deficits in the FT-Q group than in the PT-Q group. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A total of 26 patients who underwent ACLR with either an FT-Q or PT-Q graft were recruited between June 2021 and November 2021. Patients underwent isokinetic knee extension testing at > 1 year after surgery. Mixed repeated-measures analysis of covariance with least square difference post hoc testing was used to determine significant differences or interactions for all variables. RESULTS: Peak torque was significantly lower for the operated limb than the nonoperated limb in the FT-Q group (mean difference [MD] ± standard error [SE], -38.6 ± 8.3 Ncm [95% CI, -55.7 to -21.5 Ncm]; P < .001; d = 0.90) but not in the PT-Q group (MD ± SE, -7.3 ± 7.7 Ncm [95% CI, -23.2 to 8.5 Ncm]; P = .348; d = 0.20). Similarly, average power for the operated limb was lower than that for the nonoperated limb in the FT-Q group (MD ± SE, -53.6 ± 13.4 W [95% CI, -81.3 to -26.9 W]; P < .001; d = 0.88) but not in the PT-Q group (MD ± SE, -4.1 ± 12.4 W [95% CI, -29.8 to 21.5 W]; P = .742; d = 0.07), and total work was lower for the operated limb compared with the nonoperated limb in the FT-Q group (MD ± SE, -118.2 ± 27.1 J [95% CI, -174.3 to -62.2 J]; P < .001; d = 0.96) but not in the PT-Q group (MD ± SE, -18.3 ± 25.1 J [95% CI, -70.2 to 33.6 J]; P = .472; d = 0.15). CONCLUSION: The FT-Q group showed significant deficits in the operated limb compared with the nonoperated limb for all isokinetic variables. In contrast, no significant differences were found between the nonoperated and operated limbs for the PT-Q group.


Asunto(s)
Lesiones del Ligamento Cruzado Anterior , Humanos , Lesiones del Ligamento Cruzado Anterior/cirugía , Estudios de Cohortes , Músculo Cuádriceps , Tendones/trasplante , Articulación de la Rodilla/cirugía , Fuerza Muscular
20.
J Orthop ; 35: 111-114, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36467428

RESUMEN

Background: While numerous studies have evaluated National Football League injuries, there is limited literature evaluating hamstring injuries sustained in games. Our primary aim is to analyze the effect of player position on the relative incidence of hamstring injuries in the National Football League. Our secondary aims are to analyze the effects of field surface, week of the season, and short rest weeks. Methods: Official National Football League game books containing injury data from the 2013-2016 regular seasons were used. Data were analyzed to determine the incidence of hamstring injuries by field surface, rest, and week of the season. Field surface was considered either turf or grass. Short rest was considered four days. Relative incidence of hamstring injuries by position was performed with standardized incidence ratios. P values < 0.05 were considered statistically significant. Results: Seventy-eight qualifying hamstring injuries were identified and included in our analysis. Linebackers had the highest relative incidence per play with a standardized incidence ratio of 2.02 (CI: 1.14-2.91), followed by Defensive Backs (1.62; 95% CI: 1.14-1.62). Offensive linemen and defensive linemen had standardized incidence ratios significantly less than 1. Fifty-seven percent of hamstring injuries occurred on turf fields (p = 0.082). There was no significant difference between the proportion of hamstring injuries that occurred on short rest and the proportion of games played on short rest (p = 0.959). Hamstring injuries were not more likely to occur than the pooled group of all other types of injuries on short rest (p = 0.861). With a 17-week season, the mean week of hamstring injury was 8.05 (95% CI: 7.06-9.04), while the median week was 7.5. Conclusions: Linebackers and Defensive Backs have the highest relative incidence of hamstring injuries compared to other position groups, while offensive and defensive linemen have the lowest. Field surface and a short rest period did not show significance.

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