Subsequent Injury Research Articles

Deferoxamine Prevents Neonatal Posthemorrhagic Hydrocephalus Through Choroid Plexus-Mediated Iron Clearance.

Posthemorrhagic hydrocephalus occurs in up to 30% of infants with high-grade intraventricular hemorrhage and is associated with the worst neurocognitive outcomes in preterm infants. The mechanisms of posthemorrhagic hydrocephalus after intraventricular hemorrhage are unknown; however, CSF levels of iron metabolic pathway proteins including hemoglobin have been implicated in its pathogenesis. Here, we develop an animal model of intraventricular hemorrhage using intraventricular injection of hemoglobin at post-natal day 4 that results in acute and chronichydrocephalus, pathologic choroid plexus iron accumulation, and subsequent choroid plexus injury at post-natal days 5, 7, and 15. This model alsoresults in increased expression ofaquaporin-1, Na+/K+/Cl- cotransporter 1, andNa+/K+/ATPase on the apical surface of the choroid plexus 24h post-intraventricular hemorrhage. We use this model to evaluate a clinically relevant treatment strategy for the prevention of neurological sequelae afterintraventricular hemorrhageusing intraventricular administration of the iron chelator deferoxamine at the time of hemorrhage. Deferoxamine treatment prevented posthemorrhagic hydrocephalus for up to 11days after intraventricular hemorrhage and prevented the development of sensorimotor gating deficits. In addition, deferoxamine treatment facilitated acute iron clearance through the choroid plexus and subsequentlyreduced choroid plexus iron levels at 24hwith reversal of hemoglobin-induced aquaporin-1 upregulation on the apical surface of the choroid plexus. Intraventricular administration of deferoxamine at the time of intraventricular hemorrhage may be a clinically relevant treatment strategy for preventing posthemorrhagic hydrocephalus and likely acts through promoting iron clearance through the choroid plexus to prevent hemoglobin-induced injury.

Frailty in mid-life predicts outcome following trauma.

Midlife adults (50-64 y) are at risk for falls and subsequent injury; yet current guidance on fall screening only pertains to older adults (> 65 y). Herein, we evaluated whether frailty was predictive of readmission for falls in midlife trauma patients. This was a retrospective cohort study of trauma midlife patients admitted for traumatic injuries from 2010 to 2015. Demographics, injury data, fall history, and post-index readmission for falls were collected from medical records. Frailty scores were calculated retrospectively using the Canadian Study of Health and Aging Clinical Frailty Scale (CSHA-CFS). The association between frailty and outcomes was assessed. p < 0.05 was considered significant. A total of 326 midlife patients were included, 54% were considered fit, 33.7% pre-frail, and 12.3% frail. Compared to their fit and pre-frail counterparts, frail patients were more likely to be female (67.5% vs. 46.3% vs. 36.3%, p < 0.001), have a history of fall (22.5% vs. 15.5% vs. 6.2%, p < 0.001), and to have suffered a ground level fall on index admission (52.5% vs. 20% vs. 5.7%, p < 0.001). Controlling for age, BMI, gender, race, and fall history, frailty was associated with readmission of midlife adults for falls (OR = 1.82 [1.23-2.69]; p = 0.003) and discharge to skilled nursing facilities (OR = 26.86 [8.03-89.81], p < 0.001). Pre-injury frailty may be an effective tool to predict risk of readmission for fall and discharge disposition in midlife trauma patients.

Sub-chronic, low dose co-exposure to Aflatoxin B1 and Microcystin-LR in C57BL/6 mice significantly alters the cytokine response in serum and liver

ABSTRACT In this study, we examined the expression of 11 cytokines in liver and serum of C57BL/6 mice upon single or co-exposed to Aflatoxin B1 and Microcystin-LR at low-dose and sub-chronic conditions. The objective is to elucidate the potential combined hepatotoxic effects induced by AFB1+MC-LR, and we aim to provide references for further immune impacts in the liver. Luminex-based cytokine examination was applied, and we found that most of the cytokine expression increased with time. The level of IL-18, GM-CSF, IFN-γ, IL-1β and IL-4 in the liver showed a significant rise. However, some cytokines (IL-13) showed an upward trend after being suppressed during the middle stage of exposure. The level of IFN-γ and IL-12p70 generally represented the immune response in the combined exposure group. Conclusionally, there are many uncertainties due to sub-chronic and low-dose exposure. Therefore, the occurrence of subsequent irreversible liver injury and liver cancer is a probabilistic event.

2022 ISFM/AAFP Cat Friendly Veterinary Environment Guidelines.

The '2022 ISFM/AAFP Cat Friendly Veterinary Environment Guidelines' (hereafter the 'Cat Friendly Veterinary Environment Guidelines') describe how the veterinary clinic environment can be manipulated to minimise feline patient distress. Many components of a veterinary clinic visit or stay may result in negative experiences for cats. However, much can be done to improve a cat's experience by making the veterinary clinic more cat friendly. Exposure to other cats and other species can be reduced, and adjustments made with consideration of the feline senses and species-specific behaviour. Caregivers can prepare cats for a clinic visit with appropriate advice. Waiting rooms, examination rooms, hospital wards and other clinic areas can be designed and altered to reduce stress and hence encourage positive emotions. Changes need not be structural or expensive in order to be effective and make a difference to the cats and, in turn, to cat caregivers and the veterinary team. Moreover, by improving the all-round experience at the veterinary clinic, there are positive effects on preventive healthcare, identification of and recovery from illness, and compliance with treatment. Good feline healthcare necessitates visiting the veterinary clinic, which, simply by being outside of a cat's territory and familiar surroundings, may lead to negative experiences. Such experiences can trigger negative (protective) emotions and associated physiological stress, which can result in misleading clinical findings, patient distress, prolonged recovery from illness, further difficulties with handling at subsequent visits and potential veterinary personnel injury. There may be a mistaken belief that veterinary clinics must undergo significant renovation or building work to become cat friendly, and that, if species cannot be separated, then clinics cannot improve their care of cats. These Guidelines aim to dispel any such misconceptions and provide detailed practical advice. These Guidelines have been created by a Task Force of experts convened by the International Society of Feline Medicine and American Association of Feline Practitioners, based on an extensive literature review and, where evidence is lacking, the authors' experience. Endorsements: These Guidelines have been endorsed by a number of groups and organisations, as detailed on page 1161 and at icatcare.org/cat-friendly-guidelines and catvets.com/environment.

Iatrogenic nerve injury in primary and revision reverse total shoulder arthroplasty

IntroductionIatrogenic nerve injury in orthopedic surgery can impair functional outcomes. During the last years, a steady increase in the number of performed reverse total shoulder arthroplasties has been reported and complications associated with this procedure are continuously described. Neurological complications, however, remain underreported. The aims of this study were to calculate the incidence of iatrogenic nerve injury after primary and revision reverse total shoulder arthroplasty in a large patient cohort, as well as identify associated patient-and surgery-related risk factors.Materials and methodsA retrospective review of our institution’s internal Reverse Total Shoulder Arthroplasty (RTSA) database from September 2005 to December 2019 was undertaken and 34 patients with iatrogenic nerve injuries were identified, resulting in a neurological complication rate of 2.6%. Group comparisons between patients with nerve injuries (n = 34) and the remaining cohort without nerve injuries (n = 1275) were performed to identify patient- and surgery-related risk factors.ResultsOf the 34 cases with iatrogenic nerve injury, damage to terminal nerve branches occurred in 21 patients, whereas a brachial plexus lesion was diagnosed in the other 13. Nerve revision surgery was necessary in four patients. At final follow-up 13 patients (45%) had residual motor deficits and 17 (59%) had residual sensory deficits. Higher numbers of previous surgeries of the affected shoulder correlated with subsequent nerve injury (p = 0.035). Operative time was significantly longer in patients, who developed a neurologic deficit, showing a correlation between duration of surgery and occurrence of nerve injury (p = 0.013). Patients with neurologic complications were significantly younger than patients without nerve damage (median 68 vs. 72 years, p = 0.017).ConclusionsIn specialists’ hands reverse total shoulder arthroplasty is a rather safe procedure regarding the risk of neurologic injury. However, multiple previous surgeries of the affected shoulder increase the risk of neurological complications. Cases with post-operative neurologic compromise are rare and usually recover well, with few patients suffering long-term functional deficits from iatrogenic nerve injury.Level of evidenceLevel III, retrospective cohort study.

Fatty hepatocyte-derived exosomal miR-122 promotes lipid synthesis and reduces immunocompetence in grass carp (Ctenopharyngodon idella)

Exosomes are nano-sized extracellular vesicles (EVs) secreted by all cell types and are a large component of the broader class of EVs, which feature a bimolecular phospholipid membrane and are critical in inter-tissue communication. Cellular crosstalk between the liver and the immune system is known to be closely mediated by exosomes. Nevertheless, information is scarce regarding the exact interaction between the lipid metabolism and inflammatory functions of exosomal microRNAs (miRNAs) in aquatic animals. The current investigation first analyzes exosomes derived from fatty hepatocytes treated with oleic acid (OA). Fatty hepatocyte-derived exosomes (OA-Exosomes, OA-Exos) were sequenced by BGISEQ-500 sequencing technology and injected intraperitoneally into the grass carp. A total of 298 differentially expressed miRNAs were characterized in the grass carp fatty hepatocyte exosomes, of which 132 were upregulated miRNAs and 166 were downregulated miRNAs. Among the top 9 upregulated miRNAs with the highest differential expression, miR-18a-5p, miR-144, miR-122, and miR-143 were primarily involved in lipid metabolism. AST levels were remarkably elevated in the OA-Exos group (P < 0.05), while it demonstrated swollen hepatocytes, vacuolar degeneration, and increased hepatic lipid droplets in this group, indicating that exosomes promoted the formation of fatty liver and subsequent liver injury. In addition, the lipid synthesis genes ACC, FAS, PPARγ and SPEBP-1 were significantly upregulated (P < 0.05), while PPARα and LPL expressions were significantly downregulated (P < 0.05) after treatment with OA-Exos and miR-122 agomir. Levels of proinflammatory mediator TNF-α, NF-κB, and IL-1β were also upregulated in the hepatopancreatic system of grass carp that received intraperitoneal injections of OA-Exos and miR-122 agomir (P < 0.05). These results suggested that the exosome of interest and its miR-122 may promote the occurrence of fatty liver and inflammation, thus laying the foundation for further studies on lipid metabolism and immune regulation of exosomes in fish.

Cardiorenal Syndrome Type 3 Review.

The management of patients with complex comorbidity involving several organ systems can use an approach focused on each organ system independently or can use an approach trying to integrate various injuries and dysfunction into a single syndrome. Cardiorenal syndromes can develop with an initial injury to either the heart or kidney and then sequential involvement of the second organ. This can occur acutely or chronically. Cardiorenal syndrome type 3 is defined by acute renal injury with subsequent cardiac injury and/or dysfunction. Studies on these patients must use strict inclusion criteria. Pavan reported information on 100 patients with acute kidney injury in India to determine the frequency of cardiorenal syndrome type 3. He excluded patients with significant prior comorbidity. The most frequent causes of acute kidney injury in these patients were drug toxicity, gastroenteritis with volume contraction, and obstetrical complications. This study included 100 patients with acute kidney injury, and 29 developed cardiorenal syndrome type 3. Important outcomes included frequent mortality and chronic renal failure. Other studies have reported that cardiorenal syndrome type 3 occurs relatively infrequently. The analysis of large data bases has demonstrated that the development of acute kidney injury in hospitalized patients has important consequences, including the development of heart failure and increased mortality, but the complexity of these cohorts makes it difficult to determine the time course for the development of multisystem disorders. The pathogenesis of cardiorenal syndrome type 3 involves mitochondrial dysfunction, immune dysregulation, and ischemia-reperfusion. Cardiac events occur secondary to fluid overload, electrolyte disorders, and uremic toxins. These patients need increased attention during hospitalization and outpatient management in an effort to slow the progression of the primary disorder and treat complications.

Posterior tibial slope (PTS) ≥ 10 degrees is a risk factor for further anterior cruciate ligament (ACL) injury; BMI is not

PurposeThis case–control study aimed to assess the influence of BMI and PTS on subsequent ACL injury affecting either ACL graft or the native ACL of the contralateral knee after primary ACL reconstruction.MethodsA retrospective case–control study was performed using a cohort of patients who underwent arthroscopic ACL reconstruction between 2010 and 2020 using the same surgical procedure: Hamstring tendon autograft. The study group (group I) included all the patients (n = 94) during this period who sustained a subsequent ACL injury. The control group (group II) consisted of 94 patients randomly selected (matched Group I in terms of sex, age, and ACL graft) who did not sustain any further ACL injury. PTS was measured by two blinded surgeons on lateral knee view radiographs of the operated knee after primary ACL. BMI in kg/m2 was measured during the preoperative anesthesia consultation. Exclusion criteria were: non-true or rotated lateral knee radiographs of the operated knee post-ACLR, associated knee ligament injury requiring surgical management, iterative knee surgeries, open growth plate, and related fracture.ResultsThe mean posterior tibial slope in group I was 7.5° ± 2.9, and 7.2° ± 2.0 in group II. A PTS angle cutoff was set at 10 degrees. The rate of patients showing a PTS ≥ 10° was significantly higher in group I compared to group II (p < 0.01). Patients with PTS ≥ 10° were 5.7 times more likely to sustain a subsequent ACL injury, (OR: 5.7 95% CI[1.858–17.486]). The Average BMI in group I was 24.5 ± 3.7 kg.m−2 compared to group II which was 23.3 ± 3.0 kg.m−2. There were no significant differences in any of the four BMI categories between both groups (p value 0.289). A series of BMI cut-offs were also analyzed at 23 to30 kg/m2, and there was no significant difference between both groups.ConclusionsA posterior tibial slope equal to or above 10 degrees measured on lateral knee radiographs was associated with 5.7 times higher risk of ACL graft rupture or contralateral native ACL injury; however, BMI was not.

Microemboli induced by air bubbles may be deposited in organs as a consequence of contamination during medical care.

Larger volumes of accidental air infused during medical care may end up as emboli while microbubbles of air are supposed to be absorbed and cause no harm. The aim of this autopsy study was to investigate if microbubbles of air accidently entering the bloodline may be detected as microemboli (ME) in tissue such as lungs, brain and heart. If so, do differences in prevalence exist between haemodialysis (HD) and amyotrophic lateral sclerosis (ALS) patients. Included were data from 44 patients treated by medical healthcare before death. Twenty-five cases had been treated with chronic HD and 19 cases died from ALS. Since air in the bloodline activates coagulation, ME could appear. To discriminate between microbubbles caused by artificial contamination during autopsy versus microbubbles deposited in vivo, tissues were stained with a polyclonal fluorescent antibody against fibrinogen, fibrin and fragments E and D. Fluorescence staining was used to visualize ME counted within 25 microscopic fields (600×) of a tissue preparation. One tissue preparation was used if available from the lung, heart and frontal lobe of the brain and in five cases also the cerebellum. Microbubbles can be verified at autopsy as ME in the lung, heart and brain in tissue from patients exposed to more extensive medical care. There were significantly more ME in the lungs versus the heart or brain. Women had fewer ME than men. The HD group had a higher median of ME per section than the ALS group (lung: 6 versus 3, P=.007; heart: 2.5 versus 1, P=.013; brain: 7.5 versus 2, P=.001) and had more sections with ME findings than the ALS group (P=.002). A correlation existed between the time on HD (months) and ME in the lungs. More ME were present in HD patients compared with those who suffered from ALS. Minimizing air contamination from syringes, infusions and bloodlines will decrease ME and subsequent tissue injury.

Systemic GDF11 replenishment ignites myocardial injury through diminishing anti-apoptotic activity of cardiac progenitor cells

Abstract Background Tissue damage due to acute myocardial infarction is caused by both the ischemic insult and subsequent reperfusion injury (I/R). Restoration of coronary blood flow accelerates cardiomyocyte death, a phenomenon referred to as reperfusion injury, the extent of which is partly modulated by cardiac progenitor cells (CPC). Development of novel therapies to reduce infarct size, the main determinant of outcome, represent a huge unmet medical need (1). Systemic levels of growth differentiation factor 11 (GDF11), a TGF-β superfamily member that shares 90% homology with myostatin, decline with age, and GDF11 replenishment by heterochronic parabiosis or systemic recombinant GDF11 (rGDF11) delivery was postulated to have rejuvenating effects (2). Purpose We aimed to probe the effects of systemic GDF11 replenishment on I/R injury and deepen insights into the molecular mechanisms involved. Methods We designed a vehicle-controlled study in which young (3–4 months) and old (22–24 months) C57Bl/6 mice were randomly assigned to either daily systemic rGDF11 or control treatment over 30 days before myocardial I/R injury was induced. Dissected hearts were subjected to in-depth profiling followed by IPA-guided -omics to identify key regulatory mechanisms. Finally, in vitro experiments on human CPCs and HL-1 cardiomyocytes were performed. Results Myocardial Gdf11 expression declined with age, whereas myostatin (Mstn) showed an opposing expression pattern (Fig. 1A), a trend similarly observed upon I/R (Fig. 1B). Surprisingly, after the 30-day study period (Fig. 1C), young and aged rGDF11-treated mice showed higher I/R-induced infarct size and serum cardiac troponin I levels than controls, despite comparable areas at risk (Fig. 1D). Importantly, while proxies of necroptosis/pyroptosis remained unchanged, rGDF11-treated animals showed reduced cardiomyocyte viability irrespective of their age (Fig. 2A). Targeted transcriptomics applied on cardiac tissues of both groups identified the CPC-marker Nkx2–5 to be differentially regulated (Fig. 2B-C), an expression pattern validated in an independent cohort at both mRNA and protein levels (Fig. 2D). In the adult myocardium, the expression of both Nkx2–5 and its cofactor Gata4 is mainly confined to CPCs; indeed, similar reductions in Nkx2–5 and Gata4 expression were observed in CPCs exposed to rGDF11 (Fig. 2E) which coincided with accelerated cardiomyocyte death if cultured in conditioned media obtained from CPCs treated with rGDF11 (Fig. 2F), pointing toward a paracrine signalling pathway. Conclusions Myocardial expression of GDF11 declines with age, and is blunted upon I/R injury, thereby opposing the expression pattern of myostatin. Surprisingly, however, systemic GDF11 replenishment by rGDF11 supplementation enhances rather than reduces myocardial infarct size through augmented apoptosis, a phenomenon mediated by diminished cardioprotective function of CPCs. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Foundation for Cardiovascular Research – Zurich Heart House

410EMF Systematic Review of Recurrent Firearm Injury Rates in the United States

410EMF Systematic Review of Recurrent Firearm Injury Rates in the United States

S51 Trends in Acute Pancreatitis With Cannabis Use Disorder and Subsequent Acute Kidney Injury in Young Adults: Evidence From Nationwide Cohort

Introduction: Cannabis has been a well-recognized etiology of acute pancreatitis (AP) over last decade with some controversies. With increased availability of cannabis for recreational and medicinal purposes in managing chronic pain, it is essential to evaluate potential risk to multi-organ system. However, there is scarcity of large-scale data on the burden and risk of AP and subsequent acute kidney injury (AKI) among cannabis users. Methods: Using weighted discharges from the National Inpatient Sample (2016-2019), young (18-44 years) patients primarily admitted for AP with concomitant cannabis use disorder (CUD) were identified. Primary endpoints included odds and trends in AP with vs. without CUD, subsequent trends in AKI with associated sex/racial disparities and all-cause mortality. Secondary endpoints included patient disposition, hospital stay, and cost. Results: Of total 395,215 AP admissions, 29,815 (7.5%) were among patients with CUD. Crude rate of AP in CUD cohort was slightly higher vs. non-CUD admissions (n=29,815, 1.4 % vs. n=365,400, 1.1%), however, with slightly lower odds when adjusted for confounders (aOR 0.94, 95%CI:0.90-0.97, p< 0.001). The AP-CUD cohort often consisted of younger (median 33 vs 35 years), male (67.5% vs. 53.9%), blacks (28.9% vs 17.6%), patients from lowest income quartile, Medicaid enrollees vs. non-CUD cohort. Alcohol abuse, smoking, and drug abuse were significant higher in the AP-CUD cohort. Rate of AKI in AP-CUD cohort was 7% vs 6.5 % in non-CUD. Interestingly, among AP-CUD cohort, the rate of AKI was higher in males (8.3%, ptrend =0.092) vs females (4.3%, ptrend =0.104) with steady trends. The burden and trend of AKI in AP-CUD cohort was higher in Hispanics (Hispanic 9.3%, black 8.6%, white 5.6%; H: 9.1% in 2016 to 11.9% in 2017 ptrend< 0.004) (Figure). There was no significant difference in all-cause mortality between CUD and non-CUD cohorts (aOR 0.40; 95%CI:0.16-1.03, p=0.058). Routine discharges and median length of stay were comparable between cohorts (3 days) with an average cost was $25,724 in the AP-CUD cohort. Conclusion: There was a higher crude rate of AP admissions in the young CUD cohort, however, when adjusted for confounders, CUD was not independently associated with higher risk of AP, subsequent inpatient mortality, or rising trends in AKI. Hispanics demonstrated concerning trends in AKI. Future studies are warranted assessing long-term impact of polysubstance use on AP admissions and outcomes.Figure 1.: Trends in Acute Kidney Injury among Acute Pancreatitis admissions with Cannabis users by sex and race.

Activation of pyroptosis and ferroptosis is involved in radiation-induced intestinal injury in mice

Radiation-induced intestinal injury (RIII) is one of the most common abdominal and pelvic radiation therapy complications. RIII seriously affects the treatment and prognosis of cancer patients, and there are no effective interventions. Radiation can cause intestinal tissue damage, inflammatory cell infiltration, and pro-inflammatory cytokine release. We established an RIII mouse model by subjecting C57BL/6 mice to abdominal irradiation. Our results show that both pyroptosis and ferroptosis play a key role in RIII. VX-765 and Ferrostatin-1 (Fer-1) can inhibit these two types of programmed cell death and ameliorate RIII, respectively. Activation of the nuclear factor-κB (NF-κB) signaling pathway exacerbates the chemotaxis of inflammatory cells. In the present study, we hypothesized that the activation of NF-κB signaling pathway plays an important role in intestinal inflammatory injury. We demonstrated that the nuclear expression levels of the NF-κB subunit p65 increased after irradiation treatment. Reduced release of inflammatory factors and intestinal tissue damage was observed after pretreatment with pyrrolidinedithiocarbamate ammonium (PDTC). Moreover, after PDTC treatment, the indicators related to pyroptosis and ferroptosis were reversed. Collectively, these results suggest that the activation of the intestinal NF-κB signaling pathway may be associated with pyroptosis, ferroptosis, and subsequent intestinal injury after irradiation.

Journal-related Activities and Other Special Activities at the 2022 American Society of Anesthesiologists Meeting

Journal-related Activities and Other Special Activities at the 2022 American Society of Anesthesiologists Meeting

Secondary brain injury after polystyrene microplastic-induced intracerebral hemorrhage is associated with inflammation and pyroptosis

Unlike regular environmental pollutants, microplastics cannot dissolve in liquids. Physical contact of microplastic (MPs) with tissue can damage tissue structure, and it is unclear how this physical secondary injury affects brain tissue. Through CTD database analysis, it was determined that cerebral ischemia may be one of the main ways of brain tissue damage caused by MPs, and inflammatory response may play a key role in it. In the present study, PS-MPs (L-PS group:1 mg/L, M − PS group:10 mg/L, H-PS group: 100 mg/L in water) were assessed to brain tissue damage in chicken after six weeks of continuous exposure. Exposure to PS-MPs caused cerebral hemorrhage as well as generation of microthrombi and loss of Purkinje cells. Intracerebral hemorrhage caused a strong infiltration of inflammatory cells and activated the ASC-NLRP3-GSDMD signaling pathway to induce pyroptosis. Disruption of mitochondrial dynamics by PS-MPs exposure disrupts mitochondrial function and activates AMPK signaling. In conclusion, this study explored the mechanism regulation of subsequent brain injury from the perspective of physical injury (cerebral hemorrhage) of PS-MPs. To provide a reference for elucidating the neurotoxicity induced by microplastic exposure.

Postural balance asymmetry and subsequent noncontact lower extremity musculoskeletal injuries among Tunisian soccer players with groin pain: A prospective case control study

BackgroundRecent studies reported postural balance disorders in patients and soccer players with groin pain (GP) compared to controls. Since postural balance asymmetry identified after an initial injury contributes for subsequent injuries, identification of this asymmetry in soccer players with GP may highlight the risk of sustaining subsequent noncontact lower extremity musculoskeletal injuries in these players. Therefore, the aims of this study were to (i) examine static and dynamic unipedal postural balance asymmetry in soccer players with GP compared to healthy ones, and (ii) quantify the risk of subsequent noncontact lower extremity injuries in these players. Research questionDo soccer players with GP exhibit higher static and dynamic unipedal postural balance asymmetry, and higher risk of sustaining subsequent injuries compared to controls? MethodsIn this prospective case control study, 27 soccer players with non-time loss GP (GP group: GPG), and 27 healthy ones (control group: CG) were enrolled. Static and dynamic unipedal postural balance asymmetry were evaluated with a force platform using symmetry index (SI), and Y-balance test (Y-BT), respectively. Additionally, subsequent noncontact lower extremity musculoskeletal injuries were tracked for 10 months. ResultsThe GPG revealed higher (p < 0.01) SI in eyes closed condition, higher (p < 0.001) side-to-side asymmetry in anterior, posteromedial and posterolateral reach distances and in composite Y-BT score compared to CG. They showed lower (p < 0.001) composite score for injured limb and higher (p < 0.001) side-to-side asymmetry in posteromedial reach distance compared to the cut-off values of 89.6 % and 4 cm, respectively. Moreover, GPG exhibited higher odds (OR= 7.48; 95 % CI = 2.15, 26.00; p < 0.01) of sustaining subsequent injuries compared to CG. SignificanceThe Y-BT should be instituted into existing pre-participation physical examinations to screen for soccer players with non-time loss GP at an elevated risk of sustaining subsequent injuries. This could help coaches and clinicians make valid return to play decisions.

The Influence of Therapeutic Exercise after Ankle Sprain on the Incidence of Subsequent Knee, Hip, and Lumbar Spine Injury.

This study aimed to investigate the burden of knee, hip, and lumbar spine disorders occurring in the year after an ankle sprain and the influence therapeutic exercise (TE) has on this burden. A total of 33,361 individuals diagnosed with ankle sprain in the Military Health System between 2010 and 2011 were followed for 1 yr. The prevalence of knee, hip, and lumbar care-seeking injuries sustained after sprain was identified. Relationships between demographic groups, ankle sprain type, and use of TE with rate of proximal injuries were evaluated using Cox proportional hazard models to determine hazard rate effect modification by attribute. The observed effect of TE for ankle sprain on rate of injury to proximal joints was evaluated using Kaplan-Meier survival analyses. Of the total cohort, 20.5% ( n = 6848) of patients sustained a proximal injury. Specifically, 10.1% of the cohort sustained a knee ( n = 3356), 2.9% a hip ( n = 973), and 10.3% a lumbar injury ( n = 3452). Less than half of the cohort received TE after initial sprain. Patients that did were less likely to have subsequent knee (HR = 0.87, 95% confidence interval [CI] = 0.80-0.94), hip (HR = 0.68, 95% CI = 0.58-0.79), or lumbar (HR = 0.82, 95% CI = 0.76-0.89) injuries. One in five individuals that sought care for an ankle sprain experienced a proximal joint injury in the following year. TE for the management of the initial ankle sprain reduced the likelihood of proximal injury diagnosis and should be considered in treatment plans for return to work and sport protocols after ankle sprains.

Natural Compounds for SIRT1-Mediated Oxidative Stress and Neuroinflammation in Stroke: A Potential Therapeutic Target in the Future.

Stroke is a fatal cerebral vascular disease with a high mortality rate and substantial economic and social costs. ROS production and neuroinflammation have been implicated in both hemorrhagic and ischemic stroke and have the most critical effects on subsequent brain injury. SIRT1, a member of the sirtuin family, plays a crucial role in modulating a wide range of physiological processes, including apoptosis, DNA repair, inflammatory response, and oxidative stress. Targeting SIRT1 to reduce ROS and neuroinflammation might represent an emerging therapeutic target for stroke. Therefore, we conducted the present review to summarize the mechanisms of SIRT1-mediated oxidative stress and neuroinflammation in stroke. In addition, we provide a comprehensive introduction to the effect of compounds and natural drugs on SIRT1 signaling related to oxidative stress and neuroinflammation in stroke. We believe that our work will be helpful to further understand the critical role of the SIRT1 signaling pathway and will provide novel therapeutic potential for stroke treatment.

Enhancing autophagy and energy metabolism in the meniscus can delay the occurrence of PTOA in ACLT rat.

Osteoarthritis (OA) is a progressive degenerative joint disease characterized by the destruction of the articular cartilage, meniscus and the like. Autophagy and cellular energy metabolism are the mechanisms by which cells maintain homeostasis. However, little is known about the effects of autophagy and cellular energy metabolism on meniscus degeneration, and the pathogenesis of posttraumatic osteoarthritis (PTOA) after the meniscal injury is rarely reported. Therefore, this study aimed to investigate the relationship between changes in autophagy and cellular energy metabolism in the meniscus following anterior cruciate ligament transection (ACLT) and PTOA induced by subsequent articular cartilage injury. In this study, we use a combination of cell experiments in vitro and animal experiments in vivo. On the one hand, cell experiment results show that inhibiting the mTORC1 signaling pathway by inhibiting the phosphorylation of S6K and AKT proteins in meniscal cells will lead to the increase of Beclin1, LC-3B, ATG12, ULK1, P62, and activate autophagy-related signaling pathways, which in turn protects the extracellular matrix component COL1 of meniscal cells from degradation by catabolic factor MMP13. In addition, it increased the generation of mitochondrial membrane potential in meniscal cells, increased the expression of anti-apoptotic factor BCL-XL, decreased the expression of pro-apoptotic factors BAD and BAX, and reduced the apoptosis of meniscal cells. More importantly, under the stimulation of inflammatory factor IL-1β, the secretion of meniscus cells can reduce the elevated levels of MMP13 and Adamts5 caused by chondrocytes affected by IL-1β. On the other hand, the results of animal experiments in vivo further proved the validity of the results of the cell experiments, and also proved that the meniscus injury did prior to the articular cartilage degeneration after ACLT. In conclusion, this study suggests that the meniscus prior to articular cartilage damage during the development of PTOA after ACLT, and that promoting autophagy and energy metabolism of meniscal cells may be a potential therapeutic target for delaying PTOA.

Initial kinematic chain injuries increase hazard of subsequent arm injuries in professional baseball pitchers.

Currently, there are few studies that have evaluated the relationship between a lower extremity or trunk injury (kinematic chain) and subsequent arm injury. The purpose of this study was (1) to investigate the relationship between initial kinematic chain (lower extremity or trunk) injury and subsequent arm injury; and (2) to investigate the relationship between initial shoulder or elbow injury and subsequent arm injury. A 7-year prospective injury risk study was conducted with Minor League Baseball pitchers. Pitches, pitching appearances, athlete exposures (AEs), and arm injuries (≥1-day time loss) were documented throughout the season. Cox survival analyses with 95% confidence intervals (95% CIs) were performed. Confounders controlled for included age, body mass index, arm dominance, pitching role, previous arm injury, number of pitching appearances, and seasonal pitch load. A total of 297 pitchers participated (total player days=85,270). Arm injury incidence was 11.4 arm injuries/10,000 AEs, and kinematic chain incidence was 5.2 injuries/10,000 AEs. Pitchers who sustained a kinematic chain injury demonstrated a greater hazard (2.6 [95% CI: 1.2, 5.6], P=.019) of sustaining an arm injury. Pitchers who sustained an initial shoulder injury demonstrated a greater hazard (9.3 [95% CI: 1.1, 83], P=.047) of sustaining a subsequent shoulder or elbow injury compared with pitchers who sustained an initial elbow injury. Pitchers who sustained an initial lower extremity or trunk injury demonstrated an increased subsequent arm injury hazard compared with pitchers who did not. Pitchers who sustained an initial shoulder injury demonstrated a greater hazard of sustaining a subsequent arm injury compared with pitchers who sustained an initial elbow injury. However, this secondary analysis should be interpreted with caution. Clinicians should monitor risk with workload accumulation, which may be related to pitching compensatory strategies in a fatigued state. Pitchers who sustain a shoulder injury should be evaluated and perform both shoulder and elbow rehabilitation strategies before return to sport.