Selenium deficiency exacerbates ROS/ER stress mediated pyroptosis and ferroptosis induced by bisphenol A in chickens thymus.

Bisphenol A (BPA) is an industrial pollutant that can cause immune impairment. Selenium acts as an antioxidant, as selenium deficiency often accompanies oxidative stress, resulting in organ damage. This study is the first to demonstrate that BPA and/or selenium deficiency induce pyroptosis and ferroptosis-mediated thymic injury in chicken and chicken lymphoma cell (MDCC-MSB-1) via oxidative stress-induced endoplasmic reticulum (ER) stress. We established a broiler chicken model of BPA and/or selenium deficiency exposure and collected thymus samples as research subjects after 42 days. The results demonstrated that BPA or selenium deficiency led to a decrease in antioxidant enzyme activities (T-AOC, CAT, and GSH-Px), accumulation of peroxides (H2O2 and MDA), significant upregulation of ER stress-related markers (GRP78, IER 1, PERK, EIF-2α, ATF4, and CHOP), a significant increase in iron ion levels, significant upregulation of pyroptosis-related gene (NLRP3, ASC, Caspase1, GSDMD, IL-18 and IL-1ß), significantly increase ferroptosis-related genes (TFRC, COX2) and downregulate GPX4, HO-1, FTH, NADPH. In vitro experiments conducted in MDCC-MSB-1 cells confirmed the results, demonstrating that the addition of antioxidant (NAC), ER stress inhibitor (TUDCA) and pyroptosis inhibitor (Vx765) alleviated oxidative stress, endoplasmic reticulum stress, pyroptosis, and ferroptosis. Overall, this study concludes that the combined effects of oxidative stress and ER stress mediate pyroptosis and ferroptosis in chicken thymus induced by BPA exposure and selenium deficiency.

Acute kidney injury: the experience of a tertiary center of Pediatric Nephrology / Insuficiência renal aguda: experiência de um centro terciário de Nefrologia Pediátrica

ABSTRACT Introduction: Acute kidney injury (AKI) is an abrupt deterioration of kidney function. The incidence of pediatric AKI is increasing worldwide, both in critically and non-critically ill settings. We aimed to characterize the presentation, etiology, evolution, and outcome of AKI in pediatric patients admitted to a tertiary care center. Methods: We performed a retrospective observational single-center study of patients aged 29 days to 17 years and 365 days admitted to our Pediatric Nephrology Unit from January 2012 to December 2021, with the diagnosis of AKI. AKI severity was categorized according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. The outcomes considered were death or sequelae (proteinuria, hypertension, or changes in renal function at 3 to 6 months follow-up assessments). Results: Forty-six patients with a median age of 13.0 (3.5-15.5) years were included. About half of the patients (n = 24, 52.2%) had an identifiable risk factor for the development of AKI. Thirteen patients (28.3%) were anuric, and all of those were categorized as AKI KDIGO stage 3 (p < 0.001). Almost one quarter (n = 10, 21.7%) of patients required renal replacement therapy. Approximately 60% of patients (n = 26) had at least one sequelae, with proteinuria being the most common (n = 15, 38.5%; median (P25-75) urinary protein-to-creatinine ratio 0.30 (0.27-0.44) mg/mg), followed by reduced glomerular filtration rate (GFR) (n = 11, 27.5%; median (P25-75) GFR 75 (62-83) mL/min/1.73 m2). Conclusions: Pediatric AKI is associated with substantial morbidity, with potential for proteinuria development and renal function impairment and a relevant impact on long-term prognosis.

RESUMO Introdução: Insuficiência renal aguda (IRA) é uma deterioração abrupta da função renal. A incidência de IRA pediátrica está aumentando em todo o mundo, em ambientes críticos e não críticos. Nosso objetivo foi caracterizar apresentação, etiologia, evolução e desfechos da IRA em pacientes pediátricos internados em um centro de atendimento terciário. Métodos: Realizamos estudo retrospectivo observacional de centro único de pacientes com idade entre 29 dias a 17 anos e 365 dias internados em nossa Unidade de Nefrologia Pediátrica, de janeiro de 2012 a dezembro de 2021, com diagnóstico de IRA. A gravidade da IRA foi categorizada de acordo com os critérios do Kidney Disease Improving Global Outcomes (KDIGO). Os desfechos considerados foram óbito ou sequelas (proteinúria, hipertensão ou alterações na função renal em avaliações de acompanhamento de 3 a 6 meses). Resultados: Incluímos 46 pacientes com idade mediana de 13,0 (3,5-15,5) anos. Cerca de metade (n = 24; 52,2%) apresentou um fator de risco identificável para o desenvolvimento de IRA. Treze pacientes (28,3%) eram anúricos; todos foram classificados como IRA KDIGO 3 (p < 0,001). Quase um quarto (n = 10; 21,7%) dos pacientes necessitaram de terapia renal substitutiva. Aproximadamente 60% (n = 26) apresentou pelo menos uma sequela, sendo proteinúria a mais comum (n = 15; 38,5%; mediana (P25-75) da relação proteína/creatinina urinária 0,30 (0,27-0,44) mg/mg), seguida de taxa de filtração glomerular (TFG) reduzida (n = 11; 27,5%; mediana (P25-75) da TFG 75 (62-83) mL/min/1,73 m2). Conclusões: A IRA pediátrica está associada à morbidade substancial, com potencial para desenvolvimento de proteinúria e comprometimento da função renal e impacto relevante no prognóstico de longo prazo.

Acute kidney injury in nonagenarians: clinical characteristics and mortality / Injúria renal aguda em nonagenários: características clínicas e mortalidade

Abstract Introduction: Nonagenarians constitute a rising percentage of inpatients, with acute kidney injury (AKI) being frequent in this population. Thus, it is important to analyze the clinical characteristics of this demographic and their impact on mortality. Methods: Retrospective study of nonagenarian patients with AKI at a tertiary hospital between 2013 and 2022. Only the latest hospital admission was considered, and patients with incomplete data were excluded. A logistic regression analysis was conducted to define risk factors for mortality. A p-value < 0.05 was considered statistically significant. Results: A total of 150 patients were included, with a median age of 93.0 years (91.2-95.0), and males accounting for 42.7% of the sample. Sepsis was the most common cause of AKI (53.3%), followed by dehydration/hypovolemia (17.7%), and heart failure (17.7%). ICU admission occurred in 39.3% of patients, mechanical ventilation in 14.7%, vasopressors use in 22.7% and renal replacement therapy (RRT) in 6.7%. Death occurred in 56.7% of patients. Dehydration/hypovolemia as an etiology of AKI was associated with a lower risk of mortality (OR 0.18; 95% CI 0.04-0.77, p = 0.020). KDIGO stage 3 (OR 3.15; 95% CI 1.17-8.47, p = 0.023), ICU admission (OR 12.27; 95% CI 3.03-49.74, p < 0.001), and oliguria (OR 5.77; 95% CI 1.98-16.85, p = 0.001) were associated with mortality. Conclusion: AKI nonagenarians had a high mortality rate, with AKI KDIGO stage 3, oliguria, and ICU admission being associated with death.

Resumo Introdução: Nonagenários constituem um percentual de pacientes internados em ascensão, sendo a injúria renal aguda (IRA) frequente nesses pacientes. Sendo assim, é importante analisar as características clínicas dessa população e seu impacto na mortalidade. Métodos: Estudo retrospectivo de pacientes nonagenários com IRA entre 2013 e 2022 em um hospital terciário. Apenas o último internamento foi considerado e pacientes com dados incompletos foram excluídos. Uma análise por regressão logística foi realizada para definir fatores de risco para mortalidade. Um valor de p < 0,05 foi considerado significativo. Resultados: Foram incluídos 150 pacientes com mediana de idade 93,0 anos (91,2-95,0) e sexo masculino em 42,7%. Sepse foi a causa mais comum de IRA (53,3%), seguida de desidratação/hipovolemia (17,7%) e insuficiência cardíaca (17,7%). Admissão na UTI ocorreu em 39,3% dos pacientes, ventilação mecânica em 14,7%, uso de vasopressores em 22,7% e realização de terapia renal substitutiva (TRS) em 6,7%. Óbito ocorreu em 56,7% dos pacientes. Desidratação/hipovolemia como etiologia da IRA foi associado a menor risco de mortalidade (OR 0,18; IC 95% 0,04-0,77, p = 0,020). Estágio KDIGO 3 (OR 3,15; IC 95% 1,17-8,47, p = 0,023), admissão na UTI (OR 12,27; IC 95% 3,03-49,74, p < 0,001) e oligúria (OR 5,77; IC 95% 1,98-16,85, p = 0,001) foram associados à mortalidade. Conclusão: Nonagenários com IRA apresentaram alta mortalidade e IRA KDIGO 3, oligúria e admissão na UTI foram associadas ao óbito.

Safety and feasibility of intravenous administration of a single dose of allogenic-Muse cells to treat human cervical traumatic spinal cord injury: a clinical trial.

INTRODUCTION: Spinal cord injury (SCI) is a devastating injury and remains one of the largest medical and social burdens because of its intractable nature. According to the recent advances in stem cell biology, the possibility of spinal cord regeneration and functional restoration has been suggested by introducing appropriate stem cells. Multilineage-differentiating stress enduring (Muse) cells are a type of nontumorigenic endogenous reparative stem cell. The positive results of Muse cell transplantation for SCI was shown previously. As a first step for clinical application in human SCI, we conducted a clinical trial aiming to confirm the safety and feasibility of intravenously injected donor-Muse cells. METHODS: The study design of the current trial was a prospective, multicenter, nonrandomized, nonblinded, single-arm study. The clinical trial registration number was JRCT1080224764. Patients with a cervical SCI with a neurological level of injury C4 to C7 with the severity of modified Frankel classification B1 and B2 were included. A primary endpoint was set for safety and feasibility. Our protocol was approved by the PMDA, and the trial was funded by the Life Science Institute, Tokyo, Japan. The present clinical trial recruited 10 participants (8 males and 2 females) with an average age of 49.3 ± 21.2 years old. All 10 participants received a single dose of allogenic CL2020 (a total of 15 × 106 cells, 2.1-2.7 × 105 cells/kg of body weight), which is a Muse cell-based product produced from human mesenchymal stem cells, by an intravenous drip. RESULTS: There were two reported severe adverse events, both of which were determined to have no causal relationship with Muse cell treatment. The change in the ISNCSCI motor score, the activity of daily living and quality of life scores showed statistically significant improvements compared to those data at the time of CL2020 administration. CONCLUSION: In the present trial, no safety concerns were identified, and Muse cell product transplantation demonstrated good tolerability. Future clinical trials with appropriate study designs incorporating a control arm will clarify the definitive efficacy of single-dose allogenic Muse cell treatment with intravenous administration to treat SCI. TRIAL REGISTRATION: jRCT, JRCT1080224764. Registered 03 July 2019, https://jrct.niph.go.jp/latest-detail/jRCT1080224764 .

Effects of PCNL under the guidance of hologram technology on stress response and renal injury factors in patients with complex kidney stones.

Background: To investigate the effect of percutaneous nephrolithotomy (PCNL) guided by holographic image technology on stress response and renal injury factors in patients with complex renal calculi. Methods: A retrospective analysis was conducted on the clinical data of 70 patients admitted to our hospital between August 2022 and June 2023 who had complex kidney stones. The patients were divided into two groups, namely, group A and group B, based on whether they received guidance from preoperative holographic imaging technology. Group A consisted of forty patients who underwent PCNL after undergoing renal CT examination prior to surgery, while Group B included thirty patients who underwent PCNL guided by holographic imaging technology. Various indexes, including operative factors, stress response, inflammatory response, renal injury factors, renal function, complication rate, and the rate of achieving complete stone clearance in a single procedure, were compared between the two groups. Results: In group B, the puncture time and operation time of the target calyces were shorter compared to group A, additionally, the intraoperative blood loss in group B was lower than that in group A (P<0.05). 24 h after surgery, group B exhibited higher levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) compared to group A, additionally, the level of malondialdehyde (MDA) in group B was lower than that in group A (P<0.05). 24 h after surgery, group B exhibited lower levels of tumor necrosis factor a (TNF-a), interleukin-6 (IL-6), IL-1, and hypersensitive C-reactive protein (hs-CRP) compared to group A (P<0.05). Furthermore, group B showed lower levels of neutrophil gelatinase-associated lipid carrier protein (NGAL), inducible protein-8-like molecule 2 (TIPE2), and b2-microglobulin (b2-MG) than group A at the 7-day mark (P<0.05). 24 h after the operation, There was no statistically significant difference observed in the levels of SCr, BUN, between group A and group B group (P > 0.05); however, exhibited lower levels of CysC compared to group A (P < 0.05). Additionally, there were no significant differences in postoperative complications between group B and group A (P>0.05). Furthermore, one month after surgery, the one-time stone clearance rate in group B was significantly higher than that in group A (P<0.05). Conclusions: PCNL under the guidance of hologram technology can shorten the time of puncture target calyce and operation, reduce the amount of intraoperative blood loss, effectively reduce the postoperative stress reaction and inflammatory reaction of patients, reduce the level of renal injury factors, improve renal function, and increase the one-time stone clearance rate.

EValuating the Effect of periopeRaTIve empaGliflOzin on cardiac surgery associated acute kidney injury: rationale and design of the VERTIGO study.

Background: Cardiac surgery-associated acute kidney injury (CSA-AKI) is a serious complication in patients undergoing cardiac surgery with extracorporeal circulation (ECC) that increases postoperative complications and mortality. CSA-AKI develops due to a combination of patient- and surgery-related risk factors that enhance renal ischemia-reperfusion injury. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) such as empagliflozin reduce renal glucose reabsorption, improving tubulo-glomerular feedback, reducing inflammation and decreasing intraglomerular pressure. Preclinical studies have observed that SGLT2i may provide significant protection against renal ischemia-reperfusion injury due to their effects on inadequate mitochondrial function, reactive oxygen species activity or renal peritubular capillary congestion, all hallmarks of CSA-AKI. The VERTIGO (EValuating the Effect of periopeRaTIve empaGliflOzin) trial is a Phase 3, investigator-initiated, randomized, double-blind, placebo-controlled, multicenter study that aims to explore whether empagliflozin can reduce the incidence of adverse renal outcomes in cardiac surgery patients. Methods: The VERTIGO study (EudraCT: 2021-004938-11) will enroll 608 patients that require elective cardiac surgery with ECC. Patients will be randomly assigned in a 1:1 ratio to receive either empagliflozin 10 mg orally daily or placebo. Study treatment will start 5 days before surgery and will continue during the first 7 days postoperatively. All participants will receive standard care according to local practice guidelines. The primary endpoint of the study will be the proportion of patients that develop major adverse kidney events during the first 90 days after surgery, defined as ≥25% renal function decline, renal replacement therapy initiation or death. Secondary, tertiary and safety endpoints will include rates of AKI during index hospitalization, postoperative complications and observed adverse events. Conclusions: The VERTIGO trial will describe the efficacy and safety of empagliflozin in preventing CSA-AKI. Patient recruitment is expected to start in May 2024.

[Role of reactive oxygen species/silent information regulator 1 in hyperoxia-induced bronchial epithelial cell injury]. / 活性氧簇/æ²‰é»˜ä¿¡æ¯è°ƒèŠ‚å› å­1在高氧致支气管上皮细胞损伤中的作用.

OBJECTIVES: To investigate the effect of reactive oxygen species (ROS)/silent information regulator 1 (SIRT1) on hyperoxia-induced mitochondrial injury in BEAS-2B cells. METHODS: The experiment was divided into three parts. In the first part, cells were divided into H0, H6, H12, H24, and H48 groups. In the second part, cells were divided into control group, H48 group, H48 hyperoxia+SIRT1 inhibitor group (H48+EX 527 group), and H48 hyperoxia+SIRT1 agonist group (H48+SRT1720 group). In the third part, cells were divided into control group, 48-hour hyperoxia+N-acetylcysteine group (H48+NAC group), and H48 group. The ROS kit was used to measure the level of ROS. Western blot and immunofluorescent staining were used to measure the expression levels of SIRT1 and mitochondria-related proteins. Transmission electron microscopy was used to observe the morphology of mitochondria. RESULTS: Compared with the H0 group, the H6, H12, H24, and H48 groups had a significantly increased fluorescence intensity of ROS (P<0.05), the H48 group had significant reductions in the expression levels of SIRT1 protein and mitochondria-related proteins (P<0.05), and the H24 and H48 groups had a significant reduction in the fluorescence intensity of mitochondria-related proteins (P<0.05). Compared with the H48 group, the H48+SRT1720 group had significant increases in the expression levels of mitochondria-related proteins and the mitochondrial aspect ratio (P<0.05), and the H48+EX 527 group had a significant reduction in the mitochondrial area (P<0.05). Compared with the H48 group, the H48+NAC group had a significantly decreased fluorescence intensity of ROS (P<0.05) and significantly increased levels of SIRT1 protein, mitochondria-related proteins, mitochondrial area, and mitochondrial aspect ratio (P<0.05). CONCLUSIONS: The ROS/SIRT1 axis is involved in hyperoxia-induced mitochondrial injury in BEAS-2B cells.

Urinary GM2AP coincides with renal cortical damage and grades cisplatin nephrotoxicity severity in rats.

Nephrotoxicity, including electrolytic disorders and acute kidney injury (AKI), limits the clinical dosage and utility of platinated antineoplastics such as cisplatin. Cisplatin nephrotoxicity embodies a tubulopathy involving the medullary S2 and S3 segments of the proximal and the distal tubules. Higher dosage extends damage over the cortical S1 segment and intensifies overall injury. However, the standard diagnosis based on plasma creatinine as well as novel injury biomarkers lacks enough pathophysiological specificity. Further granularity in the detection of renal injury would help understand the implications of individual damage patterns needed for personalized patient handling. In this article, we studied the association of urinary ganglioside GM2 activator protein (GM2AP) with the patterns of tubular damage produced by 5 and 10 mg/kg cisplatin in rats. Our results show that GM2AP appears in the urine only following damage to the cortical segment of the proximal tubule. The information provided by GM2AP is not redundant with but distinct and complementary to that provided by urinary neutrophil gelatinase-associated lipocalin (NGAL). Similarly, treatment with 150 mg/kg/day gentamicin damages the renal cortex and increases GM2AP urinary excretion; whereas renal ischemia, which does not affect the cortex, has no effect on GM2AP. Because of the key role of the cortical proximal tubule in renal function, we contend GM2AP as a potential diagnostic biomarker to stratify AKI patients according to the underlying damage and follow their evolution and prognosis. Prospectively, urinary GM2AP may help grade the severity of platinated antineoplastic nephrotoxicity by forming part of a non-invasive liquid biopsy.

Principles and Practice in Pediatric Vascular Trauma: Part 1: Scope of Problem, Team Structure, Multidisciplinary Dynamics, and Solutions.

As of 2020, penetrating injuries became the leading cause of death among children and adolescents ages 1-19 in the United States. For the patients who initially survive and receive advanced medical care, vascular injuries are a significant cause of morbidity and additionally trigger notable trauma team angst. Moreover, penetrating injuries can lead to life-threatening hemorrhage and/or limb-threatening ischemia if not addressed promptly. Vascular injury management demands timely and unique expertise, particularly for pediatric patients. As the frequency of vascular injuries requiring operative management increases, it becomes clear that an ad hoc approach is not ideal. An integrated team would provide the best approach for rapid hemorrhage control and revascularization, but the structure of vascular response teams at children's hospitals is highly variable. In part 1 of this review, we will evaluate the scope and extent of the epidemic of traumatic vascular injuries in pediatric patients, review current evidence and outcomes, discuss various challenges and advantages of different team structures, and outline potential outcome targets and pediatric vascular trauma response solutions. LEVEL OF EVIDENCE: n/a.

Neuroinflammation evoked mechanisms for neuropathic itch in the spared nerve injury mouse model of neuropathic pain.

A large portion of neuropathic pain suffering patients may also concurrently experience neuropathic itch, with a negative impact on the quality of life. The limited understanding of neuropathic itch and the low efficacy of current anti-itch therapies dictate the urgent need of a better comprehension of molecular mechanisms involved and development of relevant animal models. This study was aimed to characterize the itching phenotype in a model of trauma-induced peripheral neuropathy, the spared nerve injury (SNI), and the molecular events underlying the overlap with the nociceptive behavior. SNI mice developed hyperknesis and spontaneous itch 7-14 days after surgery that was prevented by gabapentin treatment. Itch was associated with pain hypersensitivity, loss of intraepidermal nerve fiber (IENF) density and increased epidermal thickness. In coincidence with the peak of scratching behavior, SNI mice showed a spinal overexpression of IBA1 and GFAP, microglia and astrocyte markers respectively. An increase of the itch neuropeptide B-type natriuretic peptide (BNP) in NeuN+ cells, of its downstream effector interleukin 17 (IL17) along with increased pERK1/2 levels occurred in the spinal cord dorsal horn and DRG. A raise in BNP and IL17 was also detected at skin level. Stimulation of HaCat cells with conditioned medium from BV2-stimulated SH-SY5Y cells produced a dramatic reduction of HaCat cell viability. This study showed that SNI mice might represent a model for neuropathic itch and pain. Collectively, our finding suggest that neuropathic itch might initiate at spinal level, then affecting skin epidermis events, through a glia-mediated neuroinflammation-evoked BNP/IL17 mechanism.

Carpal Tunnel Syndrome as an Atypical Presentation of Chikungunya: A Case Report.

Chikungunya virus (CHIKV) is an arbovirus endemic to tropical and subtropical regions, primarily known for causing fever and severe joint pain. However, its capacity to induce neurological complications is less frequently documented. This case report highlights a rare presentation of carpal tunnel syndrome (CTS) following CHIKV infection, expanding the spectrum of CHIKV manifestations beyond its common arthropathic effects. We detail the case of a 45-year-old male who developed acute CTS symptoms, including pain, numbness, and motor dysfunction in the right thumb, six weeks after experiencing typical CHIKV symptoms of high-grade fever and arthralgia. Despite an initial treatment regimen of corticosteroids aimed at reducing inflammation, the patient's symptoms showed minimal improvement, prompting surgical intervention. Following carpal tunnel release surgery, the patient experienced significant relief and functional recovery. This case underscores the importance of considering CHIKV in the differential diagnosis of CTS in endemic areas, particularly when preceded by typical viral infection symptoms. It also supports surgical intervention as a viable treatment option for CTS associated with CHIKV when conservative management is ineffective, highlighting the need for an interdisciplinary approach in treating atypical manifestations of CHIKV infections.

After 40 days intra-articular injury, risk profile increases linearly with time to surgery in adolescent patients undergoing primary anterior cruciate ligament reconstruction.

PURPOSE: Anterior cruciate ligament (ACL) injuries are becoming more common in youth athletes. Time-to-surgery has been shown to significantly affect the rates of concurrent injuries at the time of ACL reconstruction (ACLR). The purpose of this study was to evaluate if time-to-surgery in ACLR impacts observances of intra-articular injuries and to categorize injury profile in relation to time. METHODS: An Institutional Review Board-approved retrospective cohort study was conducted. Included subjects were aged 21 and below and underwent primary ACLR within 6 months of injury between January 2012 and April 2020. Skeletal maturity was determined via imaging. Laterality, location and severity/pattern of meniscal and chondral injuries were recorded. Multivariate logistic regression was utilized to identify risk factors for intra-articular pathology. Cut-off analyses were added to regression models to identify trends of concurrent injuries. RESULTS: Eight hundred and fifty patients met the inclusion criteria. Patients with observed articular cartilage injuries had a significantly longer time-to-surgery of 66 days (p = 0.01). Risk factors for chondral injury were time-to-surgery (p = 0.01) and skeletal maturity (p = 0.01), while medial meniscal tears were prognosticated by time-to-surgery (p = 0.03), skeletal maturity (p = 0.01) and body mass index (p = 0.00). Cut-off analysis showed that after 40 days the proportion of patients with observed chondral injury increased with time to surgery and that there were significantly different observances of chondral (p = 0.00) and medial meniscal (p = 0.03) injuries in the 6-week model, as compared to the continuous time model. CONCLUSION: Longer time-to-surgery in ACLR is associated with higher rates of concomitant intra-articular pathology, especially chondral injuries. After 40 days, the observed rates of intra-articular injury increase proportionately with time from injury. A 6-week categorical model best stratifies intra-articular injury risk profile. Risk factor analysis identified skeletally mature patients with delayed surgery of >12 weeks to be at the highest risk for both chondral and medial meniscal injuries after an ACLR. LEVEL OF EVIDENCE: Level III.

Lower cell number, lateral defect location and milder grade are associated with improved autologous chondrocyte implantation outcome.

PURPOSE: To investigate patient demographic, injury and surgery/treatment-associated factors that can influence the patient-reported outcome (Lysholm score), following autologous chondrocyte implantation (ACI) in a large, 'real-world', nonuniform, prospective data examined retrospectively. METHODS: Knee patients treated at the Robert Jones and Agnes Hunt Orthopaedic Hospital, UK, using ACI between 1996 and 2020 were eligible. All longitudinal postoperative Lysholm scores collected between 1 and 23 years after ACI treatment and before any second major procedure (e.g., arthroplasty) were included. Multilevel longitudinal models were built investigating the association of short-term (1 year) or long-term trends in Lysholm score with baseline demographic, clinical and cell-culture variables, namely age, gender, smoker status, body mass index, baseline Lysholm score, time from surgery, defect grade, diameter and location, number of defects, previous microfracture, patch/scaffold type, associated procedure(s), number of cells implanted and their passage number. RESULTS: Following filtering, 306 of the 427 knee ACI procedures reviewed were suitable for inclusion. Factors shown to result in higher postoperative Lysholm scores in the short term were lower patient age, higher baseline Lysholm scores, fewer implanted cells and a lateral femoral defect location. The factor which was associated with higher long-term postoperative Lysholm scores was a milder defect grade. Additionally, the failure rate in this cohort was explored and it was found that 73/306 (24%) of patients experienced joint failure according to our definition. Furthermore, the outcome was not influenced by coincidental procedures in this cohort of patients. CONCLUSIONS: This study has identified a number of baseline factors associated with patient-reported outcomes following ACI and shows that treatment of associated pathology at the time of surgery potentially restores patient outcomes to a similar level as those with no associated pathologies. LEVEL OF EVIDENCE: Level IV.

Greater hip internal rotation range of motion is associated with increased dynamic knee valgus during jump landing, both before and after fatigue.

PURPOSE: The aim of this study was to analyse sex-specific differences contributing to dynamic valgus in competitive soccer players before and after a standardised fatiguing protocol. METHODS: Thirty-nine healthy female and male competitive soccer players (19 females and 20 males) were recruited for the purpose of this study. Bilateral medial knee displacement (MKD) was assessed during drop jump landings using a three-dimensional motion capture system before and after a standardised fatiguing protocol. In addition, all soccer players underwent clinical examinations, including rotational hip range of motion (ROM), isokinetic strength testing and magnetic resonance imaging (MRI) of the hip and knee. Sex-specific and fatigue-dependent differences were reported, and the influence of demographic, clinical and radiographic factors on MKD was analysed via multiple linear regression models. RESULTS: Compared with male soccer players, female soccer players demonstrated a tendency towards increased MKD during drop jump landings before (p = 0.09) and after the fatiguing protocol (p = 0.04). Sex-specific differences included increased hip internal rotation (IR) ROM, decreased hip external rotation (ER) strength and increased femoral torsion in females (all p < 0.002). According to the multiple linear regression models (stepwise method), increased hip IR ROM (90° of flexion) and the non-dominant leg remained the sole independent predictors of increased MKD during drop jump landings before (p < 0.01 and p = 0.02, respectively) and after fatigue (p < 0.01 and p < 0.01, respectively). An increase in hip IR ROM in females was linearly related to MKD after fatigue (R2 = 0.25; p < 0.01). CONCLUSION: Female soccer players exhibited increased dynamic valgus before and after fatigue, which is likely attributed to joint mobility, as well as muscular and anatomical differences, such as increased hip IR ROM, reduced hip ER strength and increased femoral torsion. In particular, females with increased hip IR ROM were more susceptible to effects of fatigue on MKD, which may increase their risk for anterior cruciate ligament injury. LEVEL OF EVIDENCE: Level III.

Neurocognitive demands reduce jump distance and coordination variability of the injured leg in athletes after anterior cruciate ligament reconstruction.

PURPOSE: The study aimed to evaluate the impact of neurocognitive reliance on jump distance and lower extremity kinematics in individuals who had undergone anterior cruciate ligament reconstruction (ACLR). This was achieved by comparing hop performance under standard and neurocognitive conditions. METHODS: Thirty-two patients after ACLR and 32 healthy controls (CTRL) participated. Both groups performed a single-leg hop for distance (SLHD) and two neurocognitive hop tests, each designed to evaluate distinct aspects of neurocognition. The neurocognitive tests included the reaction SLHD (R-SLHD), measuring reaction to a central stimulus and working memory SLHD (WM-SLHD) assessing response to a memorized stimulus amidst distractor stimuli. Distances were assessed for the three-hop tests. In addition, joint kinematics were collected to calculate lower extremity coordination of the lower extremity. SLHD performance was defined as the mean hop distance per condition per leg for each participant and was analyzed using a mixed ANOVA with condition and leg as the within-subjects factors and the group (ACLR or CTRL) as the between-subjects factor. Differences in joint coordination variability were analyzed using two-sample t-test statistical parametric mapping (SPM) with linear regression. RESULTS: The WM-SLHD resulted in a significantly decreased jump distance compared with the standard hop test both for ACLR and CTRL. Furthermore, the leg difference within the ACLR group increased under higher cognitive load as tested with the WM-SLHD, indicating leg-specific adaptations in lower extremity coordination. CONCLUSIONS: Neurocognitive single-leg hop tests resulted in reduced jump distance in CTRL and ACLR. The neurocognitive hop test revealed changes in coordination variability for the CTRL and the uninjured leg of ACLR individuals, whereas the injured leg's coordination variability remained unaltered, suggesting persistent cognitive control of movements post-ACLR. LEVEL OF EVIDENCE: Level III.

Myelin endocytosis by brain endothelial cells causes endothelial iron overload and oligodendroglial iron hunger in hypoperfusion-induced white matter injury.

AIMS: Hypoperfusion induces significant white matter injury in cerebral vascular disorders, including arteriosclerotic cerebral small vessel disease (aCSVD), which is prevalent among the elderly. Iron transport by blood vessel endothelial cells (BVECs) from the periphery supports oligodendrocyte maturation and white matter repair. This study aims to elucidate the association between iron homeostasis changes and white matter injury severity, and explore the crosstalk between BVECs and oligodendroglial lineage cells. METHODS: In vivo: C57BL/6 mice were subjected to unilateral common carotid artery occlusion (UCCAO). In vitro: BVECs with myelin pretreatment were co-cultured with oligodendrocyte progenitor cells (OPCs) or organotypic cerebellar slices subjected to oxygen and glucose deprivation. RESULTS: Circulatory iron tends to be stored in aCSVD patients with white matter injury. Myelin debris endocytosis by BVECs impairs iron transport, trapping iron in the blood and away from the brain, worsening oligodendrocyte iron deficiency in hypoperfusion-induced white matter injury. Iron accumulation in BVECs triggers ferroptosis, suppressing iron transport and hindering white matter regeneration. Intranasal holo-transferrin (hTF) administration bypassing the BBB alleviates oligodendrocyte iron deficiency and promotes myelin regeneration in hypoperfusion-induced white matter injury. CONCLUSION: The iron imbalance between BVECs and oligodendroglial lineage cells is a potential therapeutic target in hypoperfusion-induced white matter injury.

Shenqi Fuzheng Injection Reduces Cisplatin-Induced Kidney Injury via cGAS/STING Signaling Pathway in Breast Cancer Mice Model.

Background: Shenqi Fuzheng Injection (SQFZ) is a traditional Chinese medicine injection consists of extracts of Codonopsis pilosula and Astragalus mongholicus. Combining SQFZ with conventional chemotherapy may improve the therapeutic efficacy and reduce side-effects of chemotherapy. However, the mechanisms of SQFZ reducing cisplatin-induced kidney injury are still unclear. Methods: The main compounds of SQFZ were identified via UPLC-Q-TOF-MS technique. Using multiple databases to predict potential targets for SQFZ. We established a breast cancer model by injecting 4T1 cells into mice. Tumor growth and body weight were observed. Serum blood urea nitrogen (BUN), creatinine (CRE), and glutathione (GSH) levels were measured. The extent of their kidney injury was measured by hematoxylin-eosin staining (HE). Cell apoptosis was identified using Hoechst33258 staining, flow cytometry and TUNEL. We evaluated H2AX and stimulator of interferon genes (STING) expression by immunohistochemistry (IHC), and assessed apoptosis-associated proteins by Western blotting analysis. We also evaluated mitochondrial function. The secretion of the inflammatory cytokines in serum was observed using ELISA assay. The effect of the STING pathway in HK-2 renal tubular epithelial cells exposed to cisplatin alone or combined with SQFZ. Results: The potential targets of SQFZ on kidney injury mainly related to inflammatory responses, oxidation and antioxidant, apoptosis as well as IFN signaling pathway. Cisplatin significantly reduced animal weight, while there were no changes in the combination SQFZ and cisplatin. SQFZ counteracted cisplatin-induced BUN and CRE elevation. SQFZ ameliorated the oxidative stress induced by cisplatin. It diminished cisplatin-induced apoptosis and mitochondrial DNA damage and reversed cisplatin-induced cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)/STING signaling pathway activation. It also improved the mitochondrial dysfunction induced by cisplatin. Conclusions: The results of the present study suggested that SQFZ effectively reduced cisplatin-induced kidney injury by inhibiting cGAS/STING signaling pathway.

INTRATHECAL BACLOFEN FOR NEUROFIBROMATOSIS RELATED SPINAL CORD INJURY WITH SPASTICITY - A CASE REPORT.

This case presents a 35-year-old male with spinal predominant neurofibromatosis-1 who developed an incomplete spinal cord injury (C3 Asia C) which did not improve despite urgent decompressive surgery for multiple cervical neurofibromas. This report outlines a novel indication for intrathecal baclofen. The patient suffered from lower limb weakness with severe spasticity and required assistance of at least two for all activities. The aim of rehabilitation was to improve overall tone while focusing on independence, mobility and quality of life. After a successful trial of intrathecal baclofen, he underwent implantation of an intrathecal baclofen pump. The dose was gradually increased while he received a progressive programme of stretching and functional rehabilitation therapy. After 6 weeks, his MAS had improved to 1-2/4 and he had progressed to independent transfers, independence for most activities of daily living and was able to discharge to his family home with minimal support.

Neurofibromatosis type 1 is a rare disorder causing various skin, skeletal, and neurological issues, including spinal cord injury due to tumours and severe scoliosis. Current treatment is supportive, with surgery sometimes needed for acute injuries. Spasticity, a common complication, leads to functional impairments and reliance on medications with side effects. Intrathecal baclofen pumps offer a targeted solution, delivering baclofen directly into the spine to reduce side effects. We present a case where a gentleman with neurofibromatosis-1-related spinal cord injury received intrathecal baclofen, coupled with intensive rehabilitation, to enhance comfort and daily independence. This case showcases the potential of intrathecal baclofen in managing spasticity in neurofibromatosis-1-related spinal cord disease.

Management of urological injuries following gynecologic and obstetric surgery: A retrospective multicenter study.

OBJECTIVE: Urinary system injuries may occur iatrogenically during some surgical procedures especially gynecological and obstetrical surgeries. Unfortunately, these injuries can lead to serious complications in patients. In this multicentric study, we aimed to review and report our experiences and results of urinary tract injuries identified during gynecological and obstetrical surgery. METHODS: We included women with urinary tract injuries during gynecological and obstetrical surgeries between January 2018 and October 2023 at four centers. Detailed data collected include patient demographics, surgical details, injury characteristics, diagnostic and treatment methods, timing of injury diagnosis and management reports of the patients. The incidence of bladder and ureter injuries was evaluated and the rate of intraoperative urological consultations was recorded. RESULTS: In a total of 328 patients with a median age of 47 years (24-90), urinary tract injuries were diagnosed, including 227 (69.2%) iatrogenic bladder injuries (IBI) and 101 (30.8%) iatrogenic ureteral injuries (IUI). These injuries were diagnosed in 299 patients (91.2%) during surgery and in 29 patients (8.8%) after the surgical procedure. We observed intraoperative detection rates of 71.9% for IBI and 28.1% for IUI. IBI (71.9%) was diagnosed significantly more frequently than IUI (28.1%) (p=0.001). Cesarean section resulted in significantly more frequent IBI, whereas tumor debulking surgeries resulted in more IUI (n=52, 56.5%) than the other types of procedures (p<0.001). CONCLUSION: Our study provides a comprehensive overview of iatrogenic urological injuries during gynecological and obstetrical surgeries. Although the bladder is the most frequently injured organ during gynecological and obstetric surgeries, early diagnosis and urological intervention are mandatory to prevent delayed complications. Surgeons must have a thorough understanding of the pelvic anatomy and appropriate surgical techniques to prevent iatrogenic injuries during surgery and ensure timely diagnosis and treatment of urinary tract injuries.

Needle arthroscopic-assisted repair of tibio-fibular syndesmosis acute injury: A case report.

BACKGROUND: Acute injuries to the tibiofibular syndesmosis, often associated with high ankle sprains or malleolar fractures, require precise diagnosis and treatment to prevent long-term complications. This case report explores the use of needle arthroscopy as a minimally invasive technique for the repair of tibiofibular syndesmosis injuries. CASE SUMMARY: We report on a 40-year-old male patient who presented with a trimalleolar fracture and ankle subluxation following a high ankle sprain. Due to significant swelling and poor soft tissue quality, initial management involved external stabilization. Subsequently, needle arthroscopy was employed to assess and treat the tibiofibular syndesmosis injury. The procedure, performed under spinal anesthesia and fluoroscopic control, included nanoscopic evaluation of the ankle joint and reduction of the syndesmosis using a suture button. Follow-up assessments showed significant improvement in pain levels, range of motion, and functional scores. At 26 weeks post-procedure, the patient achieved full range of motion and pain-free status. Needle arthroscopy offers a promising alternative for the management of acute tibiofibular syndesmosis injuries, combining diagnostic and therapeutic capabilities with minimal invasiveness. CONCLUSION: This technique may enhance clinical outcomes and reduce recovery times, warranting further investigation and integration into clinical practice.