Persistent Injury Research Articles

Cardiovascular complications in COVID-19: acute management, long-term sequelae, and post-acute care strategies: a brief review

Background: The COVID-19 pandemic, driven by the SARS-CoV-2 virus, has significantly impacted individuals with pre-existing cardiovascular disease (CVD), elevating their risk of severe complications and mortality. Cardiovascular complications, such as myocarditis, acute coronary syndrome (ACS), arrhythmias, and venous thromboembolism (VTE), have been widely observed in COVID-19 patients, with mechanisms including viral myocardial injury, systemic inflammation, and a hypercoagulable state. These complications not only contribute to acute morbidity but also increase the risk of long-term cardiovascular sequelae, highlighting the need for optimized post-acute care in this population. Methods and Materials: A review was conducted based on a comprehensive search strategy using the PICO framework. Studies published from December 2019 onwards, focusing on COVID-19 patients with cardiovascular complications, were identified from databases including PubMed and Google Scholar. Objectives: This review aims to evaluate the cardiovascular complications of COVID-19, with particular attention to the acute and long-term management strategies. It seeks to assess whether comprehensive post-acute care programs tailored to cardiovascular health can reduce the incidence of long-term cardiovascular events and improve outcomes compared to standard care in COVID-19 survivors with pre-existing CVD. Discussion: The findings from this review underscore the significant cardiovascular burden faced by COVID-19 patients, particularly those with pre-existing conditions. Acute complications such as myocarditis, ACS, and VTE are common, with direct myocardial injury and systemic inflammation playing critical roles. Long-term sequelae, including persistent myocardial injury, heart failure, and arrhythmias, are increasingly being recognized, necessitating specialized post-acute care interventions. Evidence suggests that comprehensive cardiovascular rehabilitation programs incorporating lifestyle modification, pharmacotherapy optimisation, and regular monitoring may improve long-term outcomes. However, further research is required to establish the most effective management strategies, particularly for high-risk groups, such as patients with pre-existing CVD and pediatric populations.

An ILC2-chitinase circuit restores lung homeostasis after epithelial injury.

Environmental exposures increase the risk for severe lung disease, but specific drivers of persistent epithelial injury and immune dysfunction remain unclear. Here, we identify a feedback circuit triggered by chitin, a common component of airborne particles, that affects lung health after epithelial injury. In mice, epithelial damage disrupts lung chitinase activity, leading to environmental chitin accumulation, impaired epithelial renewal, and group 2 innate lymphoid cell (ILC2) activation. ILC2s, in turn, restore homeostasis by inducing acidic mammalian chitinase (AMCase) in regenerating epithelial cells and promoting chitin degradation, epithelial differentiation, and inflammatory resolution. Mice lacking AMCase or ILC2s fail to clear chitin and exhibit increased mortality and impaired epithelial regeneration after injury. These effects are ameliorated by chitinase replacement therapy, demonstrating that chitin degradation is crucial for recovery after various forms of lung perturbation. Thus, the ILC2-chitinase response circuit may serve as a target for alleviating persistent postinjury lung epithelial and immune dysfunction.

Frequency of adverse perinatal outcomes in patients with pregnancy related acute renal (kidney) injury in a tertiary care hospital

Background & Objective: Pregnancy related acute kidney injury (Pr-AKI) is coupled with adverse feto-maternal outcomes. Adverse perinatal outcome comprising of still births, intrauterine growth retardation, neonatal deaths are indicators of severity of underlying obstetrical conditions ending on Pr-AKI. These perinatal outcomes can also serve as potential predictors for long term outcomes of Pr-AKI. Our study aimed to determine frequencies of adverse perinatal outcomes and to evaluate adverse perinatal outcome as predictor for persistent renal injury in patients with pregnancy induced acute renal injury (Pr-AKI). Method: A descriptive case series including 100 women with Pr-AKI, was conducted in a tertiary care hospital of Peshawar from 1st August 2021 to 31st July 2022. Included patients were followed for three months period, from their date of delivery. Adverse perinatal outcome included stillbirths, and early neonatal deaths. Results: The mean age of study sample was 29.20±6.40. The pre dominant etiology for Pr-AKI was primary postpartum hemorrhage, occurring in 52% women. Still births were seen in 48% cases, while early neonatal deaths were seen in 7% cases. Adverse perinatal outcome had statistically significant association with persistent renal failure (p-0.01). Other factors having statistically significant association with persistent renal injury (PRF) were multiparity and cesarean births. (p<0.05) Association of adverse perinatal outcome with persistent renal injury persisted on multivariate logistic regression. a OR 6.14; CI 1.15-32.29, p-0.033. Conclusion: Almost half of the cases with Pr-AKI have still births. Still birth in patients with Pr-AKI is associated with persistent renal injury at 12 weeks follow up period. doi: https://doi.org/10.12669/pjms.40.10.9228 How to cite this: Mohammad N, Qazi Q, Liaqat N. Frequency of adverse perinatal outcomes in patients with pregnancy related acute renal (kidney) injury in a tertiary care hospital. Pak J Med Sci. 2024;40(10):2267-2270. doi: https://doi.org/10.12669/pjms.40.10.9228 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

The Irony of Iron Pill Gastritis: A Case of Delayed Recognition and Persistent Injury in an Elderly Patient

The Irony of Iron Pill Gastritis: A Case of Delayed Recognition and Persistent Injury in an Elderly Patient

Persistent acute kidney injury: Postoperative impact and predictors in patients undergoing liver resection.

Persistent acute kidney injury (AKI) has not been investigated in patients undergoing liver resection. We aimed to identify the predictors of persistent AKI, its effect on postoperative outcomes and long-term renal function in patients following liver resection, and its impact on survival in patients with hepatocellular carcinoma (HCC). We examined 990 patients who underwent liver resection, including a subgroup analysis of 384 patients with curative resection for initial HCC. Persistent AKI was defined as residual impairment of serum creatinine≥0.3mg/dL or≥50% from baseline 1month after surgery. The persistent AKI group had significantly worse postoperative outcomes, including overall morbidity, major morbidity, longer hospital stay, and 90-day mortality. In the subgroup analysis of patients with HCC, persistent AKI was associated with a significantly poorer overall survival (OS) rate (p<0.001), and the multivariate analysis confirmed persistent AKI as an independent poor prognostic factor for OS (p=0.005). The long-term postoperative estimated glomerular filtration rate decline was significantly greater in the persistent AKI group than in the no AKI and transient AKI groups (p<0.001 for both). Chronic kidney disease, albumin-bilirubin grade ≥2, and anatomical resection were independent predictors of persistent AKI (p=0.001, p=0.039, and p=0.015, respectively). Persistent AKI adversely affects postoperative outcomes and long-term renal function in patients undergoing liver resection. Furthermore, it is associated with poor prognosis in patients with HCC. Therapeutic strategies to prevent persistent AKI are critical for improving postoperative outcomes in these patients.

Persistent Renal Dysfunction After Acute Kidney Injury Among STEMI Patients Undergoing Primary Coronary Intervention: Prevalence and Predictors.

Acute kidney injury (AKI) is a common and serious complication of ST-elevation myocardial infarction (STEMI). AKI and chronic kidney disease (CKD) are highly heterogeneous, leaving a wide gap between them. Therefore, the term acute kidney disease (AKD) was implemented, describing prolonged renal injury between 7 and 90 days. We aimed to evaluate the prevalence and predictors of AKD among STEMI patients. This retrospective observational study included 2940 consecutive patients admitted with STEMI between 2008 and 2022. Renal function was assessed upon admission and routinely thereafter. Renal outcomes were evaluated according to KDIGO criteria, with AKD defined as persistent renal injury of between 7 and 90 days. Two hundred and fifty-two subjects with STEMI and AKI were included; of them, 117 (46%) developed AKD. Among baseline CKD patients, higher rates of AKD were observed (60% vs. 46%). KDIGO index ≥ 2 was an independent predictor for AKD in in subjects without baseline CKD (AOR 2.63, 95% CI 1.07-6.53). In subjects with baseline CKD, older age and higher creatinine were independent predictors for AKD. Subjects with AKD had a higher 1-year mortality rate (HR 3.39, 95% CI 1.71-6.72, p < 0.01). This trend was mainly driven by the CKD subpopulation where higher mortality rates for AKD on CKD were observed (HR 5.26, 95% CI 1.83-15.1, p < 0.01). AKD is common among STEMI patients with AKI. The presence of CKD and higher KDIGO stage should prompt strict monitoring for early diagnosis, treatment, and prevention of renal function deterioration.

Rheb1 deficiency elicits mitochondrial dysfunction and accelerates podocyte senescence through promoting Atp5f1c acetylation

Podocyte senescence can cause persistent podocyte injury and albuminuria in diabetic kidney disease (DKD), but the mechanism remains obscure. In this study, podocyte senescence was confirmed by immunohistochemical staining in podocytes from patients and mice with DKD. Rheb1 knockout in podocytes aggravated podocyte senescence and injury in diabetic mice, but mitigated podocyte injury in mice with podocyte-specific mTORC1 activation induced by Tsc1 deletion. In cultured podocytes, Rheb1 knockdown remarkably accelerated podocyte senescence, independent of mTORC1. Mechanistically, PDH phosphorylation in podocyte was correlated with podocyte senescence in DKD patients. Rheb1 deficiency decreased ATP, mitochondrial membrane potential and partial components of respiratory chain complex, and enhanced ROS production and PDH phosphorylation, which indicates mitochondrial dysfunction, both in vitro and in vivo. Furthermore, Rheb1 interacted with Atp5f1c, and regulated its acetylation under a high-glucose condition. Together, Rheb1 deficiency elicits mitochondrial dysfunction and accelerates podocyte senescence through promoting Atp5f1c acetylation, in an mTORC1-independent manner, which provides experimental basis for the treatment of DKD.

The processing mechanism of vinegar-processed Curcumae Rhizome enhances anti hepatic fibrotic effects through regulation of PI3K/Akt/mTOR signaling pathway

BackgroundHepatic fibrosis, a chronic pathological condition resulting from various forms of persistent liver injury, in the later stage, it can evolve into cirrhosis and even liver cancer. Curcumae Rhizoma (CR), traditionally recognized for its properties in line qi break blood, eliminate accumulation and relieve pain. According to traditional Chinese medicine (TCM) principles, vinegar-processing enhances CR's ability to enter the liver meridian and act on the blood level, potentially augmenting its therapeutic effects on hepatic diseases. Therefore, vinegar-processed Curcumae Rhizoma (VCR) is frequently employed in treating liver fibrosis and related hepatic conditions. However, the underlying mechanisms of vinegar processing in enhancing its therapeutic efficacy remain unclear. MethodsThe anti-liver fibrosis effects of CR and VCR were verified at individual and cellular levels. Subsequently, HPLC-Q-TOFMS and pharmacokinetic analysis were utilized to elucidate the potential bioactive substances underlying the enhanced anti-fibrotic efficacy of VCR. Building upon these findings, network pharmacology and metabolomics were integrated to screen for key effect components and regulatory pathways. Finally, the mechanisms of action were further analyzed and validated at the tissue and cellular levels through Western blotting (WB) and molecular docking studies. ResultsBoth CR and VCR exhibited therapeutic effects against hepatic fibrosis, with VCR demonstrating enhanced efficacy after vinegar processing. 6 sesquiterpenes including furanodiene and curdione, showed significant alterations in plasma exposure and hepatic distribution post-processing. VCR significantly improved pathological liver conditions, lipid accumulation, and fibrosis severity. Additionally, VCR markedly reduced the expression of α-SMA in the liver and attenuated the elevations in liver function markers such as ALT and AST. Combined network pharmacology, metabolomics, and hepatic tissue WB analysis revealed that the reduced phosphorylation of the PI3K/Akt/mTOR pathway is a critical mechanism in VCR's anti-fibrotic effects. Experiments on LX-2 cells demonstrated that four sesquiterpenes, including furanodiene and curdione, effectively inhibited the proliferation of activated hepatic stellate cells (HSCs). Furanodiene, in particular, promoted apoptosis in activated HSCs by reducing phosphorylation levels of the PI3K/Akt/mTOR pathway proteins, increasing BAX expression, and activating downstream caspase-3 to achieve the effect of anti-liver fibrosis. ConclusionVinegar-processing significantly increases the plasma exposure and hepatic distribution of components such as furanodiene in VCR, enhancing anti-fibrotic efficacy by downregulating the phosphorylation levels of the PI3K/Akt/mTOR pathway and promoting HSC apoptosis. This study provides a comprehensive explanation of the vinegar-processing mechanism and its role in enhancing the anti-fibrotic effects of VCR, offering insights for its clinical application in liver fibrosis treatment and reference for the mechanistic study of other vinegar-processed herbal medicines.

PASS: A scoring system to evaluate persistent kidney injury in critically ill ICU adult patients

Background We evaluated if the course of recovery from sepsis-induced acute kidney injury (AKI) can be predicted using variables collected at admission. Methods A total of 63 patients admitted for sepsis-induced AKI in our Mangalore ICU were evaluated and baseline demographic and clinical/laboratory parameters, including serum creatinine (SCr), base excess (BE), Plethysmographic Variability Index (PVI), Caval Index, R wave variability index (RVI), mean arterial pressure (MAP) and renal resistivity index (RI) using renal doppler and need for inotropes were assessed on admission. Patients were managed as per standard protocol. After six hours of fluid resuscitation, patients were classified as volume responders or non-responders. Re-assessment was done at 24 hours and 72 hours after admission. Primary outcome was persistent AKI after 72 hours. Secondary outcome was initiation of dialysis or death within 15 days of admission. Results A total of 34 subjects recovered from AKI, of whom 32 patients were volume responders and 31 were non-responders. Response to fluid, MAP at admission and six hours, BE at admission, inotrope requirement, and PVI at admission did not correlate with recovery. Multiple logistic regression showed that SCr &lt; 2.36 mg%, RVI &gt; 14.45 and RI &lt; 0.8 on admission correlated with recovery and they were evaluated further to model AKI recovery and develop PASS. PASS score = (SCr points × 5.4) + (RVI points × 4.0) + (RI points × 6.2). One point each was allotted if SCr was &lt; 2.36, RVI was &gt; 14.45 and RI was &lt;0.8, and 0 otherwise. A score &gt; 7.8 predicted recovery with a sensitivity of 79.4%, specificity of 72.4%, PPV 81.8%, NPV 76.7% and AuROC of 0.85. Conclusions The PASS score can be used to identify salvageable cases of sepsis-AKI, guiding fluid resuscitation and aiding early referral from rural to tertiary care centers for better management.

L4-L5 anatomy classification system for lateral lumbar interbody fusion.

Lateral lumbar interbody fusion (LLIF), developed by Dr. Luiz Pimenta in 2006, allows access to the spinal column through the psoas major muscle. The technique has many advantages, such as reduced bone and muscular tissue damage, indirect decompression, larger implants, and lordosis correction capabilities. However, this technique also has drawbacks, with the most notorious being the risk of spinal pathologies due to indirect injury of the lumbar plexus, but with low rates of persistent injuries. Therefore, several groups have proposed classifications to help identify patients at a greater risk of presenting with neurological deficits. The present work proposes a classification system that relies on simple observation of easily identifiable key structures to guide lateral L4-L5 LLIF decision-making. Patients aged > 18 years who underwent preoperative magnetic resonance imaging (MRI) between 2022 and 2023 were included until 50 high-quality images were acquired. And excluded as follow Anatomical changes in the vertebral body or major psoas muscles prevent the identification of key structures or poor-quality MRIs. Each anatomy was classified as type I, type II, or type III according to the consensus among the three observers. Fifty anatomical sites were included in this study. 70% of the L4-L5 anatomy were type I, 18% were type II, and 12% were type III. None of the type 3 L4-L5 anatomies were approached using a lateral technique. The proposed classification is an easy and simple method for evaluating the feasibility of a lateral approach to-L4-L5.

HCC-1 Accelerates Atherosclerosis by Inducing Endothelial Cell and Macrophage Pyroptosis and Serves as an Early Diagnostic Biomarker.

HCC-1 (hemofiltrate CC chemokine-1), a CC-type chemokine, exerts function to change intracellular calcium concentration, induce leukocyte, and manipulate enzyme release especially in monocytes. It has been reported that HCC-1 can predict the persistent acute kidney injury or suppress hepatocellular carcinoma by modulating cell cycle and promoting apoptosis; however, the effect of HCC-1 on atherosclerosis is poorly understood. Here, we aimed to clarify the function and mechanism of HCC-1 in atherosclerosis and whether it could serve as a novel biomarker for the diagnosis of atherosclerosis. HCC-1 expression in serum, atherosclerotic plaques, and normal arterial tissue from patients with atherosclerosis and control group was assessed by ELISA, immunohistochemistry and confocal microscope, and bioinformatic analysis. The atherosclerotic model of HCC-1 overexpressing and control mice was generated by tail vein injection of adeno-associated virus serotype 9-HCC-1 on an ApoE-/- background. Cell adhesion, polarization, and pyroptosis were evaluated in vitro. The relationship between HCC-1 concentration in serum and atherosclerosis was analyzed in patients with atherosclerosis. HCC-1 expression was positively correlated with the occurrence and stable-unstable switch of atherosclerosis under bioinformatic analysis, which is further supported by the results of increased HCC-1 expression in atherosclerosis patients both in serum and atherosclerotic plaque. adeno-associated virus serotype 9-HCC-1 mice had higher levels of inflammatory factors, increased macrophage accumulation and pyroptotic rate in plaque, and decreased atherosclerotic plaque stability. In vitro, HCC-1 promoted monocyte adhesion and M1 polarization and induced inflammation and pyroptosis both in endothelial cells and macrophages. HCC-1 expression was increased in patients with atherosclerosis, and HCC-1 overexpression accelerated atherosclerotic burden via an enhancement in monocyte recruitment, M1 polarization, and pyroptosis both in endothelial cells and macrophages. Our findings suggested that HCC-1 may serve as an early biomarker for the diagnosis of atherosclerosis, with the capacity to reflect the degree of stenosis.

Is it possible to predict persistent acute kidney injury in critically ill patients with COVID-19 infection?

Critically ill patients with coronavirus disease 2019 (COVID-19) often face a heightened risk of morbidity and mortality, particularly due to complications such as acute kidney injury (AKI). While the persistent acute kidney injury risk index (PARI) has shown promise in predicting the risk of persistent AKI (pAKI) in non-COVID patients, its effectiveness in critically ill COVID-19 patients remains to be explored. We aimed to evaluate the predictive power of the PARI in identifying pAKI and its prognostic significance in terms of clinical outcomes. This was a single-center retrospective study of patients with COVID-19 admitted at our 36-bed tertiary intensive care unit between April and December 2020. There were 152 patients who fulfilled our inclusion criteria. Fifty seven (37.5%) had developed AKI and 16 (10.25%) had developed pAKI. Vasopressor, mechanical ventilation and renal replacement therapy (RRT) requirement, sequential organ failure assessment (SOFA), and PARI were significantly higher in patients who developed pAKI than those who did not. The PARI were significantly higher in patients with short-term mortality compared to survivors. The area under the receiver operating characteristic (ROC) curve (AUC) of the PARI score for predicting pAKI was 0.66 (95% CI: 0.53-0.79), whereas short-term mortality was 0.733 (95% CI, 0.65-0.81). The PARI score was evaluated as simple, useful, and reliable in predicting pAKI in severe cases with COVID-19; and therefore, pAKI and its related RRT complications can be prevented with protective interventions. Further comprehensive studies are warranted to deepen our understanding of this relationship.

Risk Factors and Outcomes Associated With the Development of Persistent Acute Kidney Injury in Non-Renal Solid Organ Transplant Recipients: Systematic Review and Meta-Analysis.

Persistent acute kidney injury (pAKI), compared with acute kidney injury (AKI) that resolves in <72h, is associated with worse prognosis in critically ill patients. Definitions and prognosis of pAKI are not well characterized in solid organ transplant patients. Our aims were to investigate (a) definitions and incidence of pAKI; (b) association with clinical outcomes; and (c) risk factors for pAKI among heart, lung, and liver transplant recipients. We systematically reviewed the literature including PubMed, Embase, Web of Science, and Cochrane from inception to 8/1/2023 for human prospective and retrospective studies reporting on the development of pAKI in heart, lung, or liver transplant recipients. We assessed heterogeneity using Cochran's Q and I2. We identified 25 studies including 6330 patients. AKI (8%-71.6%) and pAKI (2.7%-55.1%) varied widely. Definitions of pAKI included 48-72h (six studies), 7days (three studies), 14days (four studies), or more (12 studies). Risk factors included age, body mass index (BMI), diabetes, preoperative chronic kidney disease (CKD), intraoperative vasopressor use, and intraoperative circulatory support. pAKI was associated with new onset of CKD (odds ratio [OR] 1.41-11.2), graft dysfunction (OR 1.81-8.51), and long-term mortality (OR 3.01-13.96), although significant heterogeneity limited certainty of CKD and graft dysfunction outcome analyses. pAKI is common and is associated with worse mortality among liver and lung transplant recipients. Standardization of the nomenclature of AKI will be important in future studies (PROSPERO CRD42022371952).

Predictive value of renal resistive index combined with plasma biomarkers of endothelial cell activation for persistent acute kidney injury in patients with septic shock

AbstractObjectiveTo assess the predictive abilities of Doppler‐based resistive index and plasma biomarkers of endothelial cell activation in identifying persistent acute kidney injury (pAKI) among patients with septic shock.MethodPatients diagnosed with septic shock were categorized into none AKI (n = 25), transient AKI (tAKI, n = 47), and pAKI (n = 48) groups. Kidney function parameters (urine output, serum creatinine, and serum urea) were measured within the initial 24 h upon intensive care unit (ICU) admission. The Doppler‐based resistive index, and the plasma biomarkers [fractalkine, soluble E‐Selectin (sE‐Selectin), and soluble intercellular adhesion molecule‐1 (sICAM‐1)] were evaluated upon admission to the ICU.ResultsThe predictive capacity of Doppler‐based resistive index for distinguishing pAKI at day 3 from none AKI/tAKI in septic shock patients was moderate, with sensitivity of 47.92% and specificity of 76.39%. Fractalkine levels displayed significant differences across groups and exhibited a favorable predictive ability for pAKI at day 3 (AUC = 0.800), while sE‐Selectin and sICAM‐1 showed moderate predictive abilities (AUC = 0.636 and 0.634, respectively). Comparative analysis of predictive models demonstrated that incorporating kidney function parameters, Doppler‐based resistive index, and plasma biomarkers yielded the highest AUC of 0.903, followed closely by the model utilizing serum creatinine, urine output, and plasma fractalkine, with an AUC of 0.896.ConclusionIntegrating kidney function parameters, along with Doppler‐based resistive index and plasma biomarkers of endothelial cell activation, yielded the strongest predictive model for pAKI. Additionally, the combination of serum creatinine, urine output, and plasma fractalkine shows promise in risk assessment and management strategies for pAKI.

Post-traumatic cognitive disorders: the cholinergic therapy options

Traumatic brain injury (TBI) is one of the most common causes of neurological disability in young and middle-aged people. Cognitive impairment is the most persistent and universal brain injury syndrome in cases of TBI and, moreover, the best indicator of TBI severity to predict its outcome. Cognitive impairment can persist persistently even after mild TBI, which accounts for 70–90 % of the total number of trauma patients. This may be due to the fact that in cases of mild TBI, the most fragile functions of integrative structures of the frontal and temporal lobes are slowly and not always completely recovered and the dominant clinical manifestation become complex neuropsychological disorders. Individuals with repeated mild TBI are characterized by development of chronic post-traumatic encephalopathy, that is a kind of neurodegenerative disease manifested by slowly increasing cognitive impairment, parkinsonism and a number of other neurological syndromes. Early detection and adequate correction of the cognitive impairments may improve the outcome of injury of diverging severity. Due to the fact that the pathogenesis of TBI is based on disorder of cholinergic system, the patients have predominance of regulatory disorders in the neuropsychological profile, as well as a combination of cognitive and affective disorders. Administration of acetylcholine precursors leads to rapid increase of free choline levels in plasma that penetrates the blood-brain barrier well and enhances cholinergic activity by increasing acetylcholine synthesis and release. The article considers the possibilities of using acetylcholine precursors in connection with their potential to block the progressive impairment of cognitive functions induced by trauma as well as to reduce severity of behavioral and affective disorders.

High-volume hemofiltration does not protect human kidney endothelial and tubular epithelial cells from septic plasma-induced injury

High volume hemofiltration (HVHF) could remove from plasma inflammatory mediators involved in sepsis-associated acute kidney injury (SA-AKI). The IVOIRE trial did not show improvements of outcome and organ dysfunction using HVHF. The aim of this study was to evaluate in vitro the biological effects of plasma of patients treated by HVHF or standard volume hemofiltration (SVHF). We evaluated leukocyte adhesion, apoptosis and functional alterations of endothelial cells (EC) and tubular epithelial cells (TEC). In vitro data were correlated with plasma levels of TNF-α, Fas-Ligand (FasL), CD40-Ligand (CD40L), von Willebrand Factor (vWF) and endothelial-derived microparticles. An experimental model of in vitro hemofiltration using LPS-activated blood was established to assess cytokine mass adsorption during HVHF or SVHF. Plasma concentrations of TNF-ɑ, FasL, CD40L and von Willebrand Factor (vWF) were elevated at the start (d1h0) of both HVHF and SVHF, significantly decreased after 6 h (d1h6), remained stable after 12 h (d1h12) and then newly increased at 48 h (d3h0). Plasma levels of all these molecules were similar between HVHF- and SVHF-treated patients at all time points considered. In addition, the levels of endothelial microparticles remained always elevated, suggesting the presence of a persistent microvascular injury. Plasma from septic patients induced leukocyte adhesion on EC and TEC through up-regulation of adhesion receptors. Moreover, on EC, septic plasma induced a cytotoxic and anti-angiogenic effect. On TEC, septic plasma exerted a direct pro-apoptotic effect via Fas up-regulation and caspase activation, loss of polarity, altered expression of megalin and tight junction molecules with an impaired ability to internalize albumin. The inhibition of plasma-induced cell injury was concomitant to the decrease of TNF-α, Fas-Ligand and CD40-Ligand levels. The protective effect of both HVHF and SVHF was time-limited, since a further increase of circulating mediators and plasma-induced cell injury was observed after 48 h (d3h0). No significant difference of EC/TEC damage were observed using HVHF- or SVHF-treated plasma. The in vitro hemofiltration model confirmed the absence of a significant modulation of cytokine adsorption between HVHF and SVHF. In comparison to SVHF, HVHF did not increase inflammatory cytokine clearance and did not reverse the detrimental effects of septic plasma-induced EC and TEC injury. Further studies using adsorptive membranes are needed to evaluate the potential role of high dose convective therapies in the limitation of the harmful activity of plasma soluble factors involved in SA-AKI.Trial registration IVOIRE randomized clinical trial; ClinicalTrials.gov (NCT00241228) (18/10/2005).

Treatment concepts for the medial clavicle and the sternoclavicular joint

Medial clavicle fractures and injuries to the sternoclavicular joint are rare injuries but can have life-threatening consequences. There are no standardized treatment algorithms or guidelines for the diagnostics and treatment. This article provides an overview of the individual topographies as well as the conservative and surgical treatment strategies.Conservative treatment is preferred for medial clavicle fractures. The indications for surgical treatment are variable but this is frequently carried out if there is a fracture displacement > 1 cm or1 shaft width and high functional demands. In the case of accompanying injuries to neurovascular structures, an open fracture or the threat of perforation of the skin, surgical treatment is mandatory. Open reduction and internal fixation using (locking) plates is currently the preferred form of treatment.In the case of posterior dislocation of the sternoclavicular joint, an immediate closed reduction must be attempted with the patient under analgosedation and with emergency treatment on standby. This temporal urgency does not exist for anterior and superior dislocations. Surgical treatment is indicated in cases of unsuccessful reduction, persistent symptomatic instability or injuries of the neurovascular bundle. From a multitude of treatment options, arthrodesis with suture cerclage has shown good results. Tendon grafts as well as special hook plates are increasingly being used due to better biomechanical qualities. The surgical treatment of combined injuries is determined by the individual injury pattern.Despite the variety of treatment strategies, the long-term outcome has consistently been positively described.

Slow rewarming after hypothermia does not ameliorate white matter injury after hypoxia-ischemia in near-term fetal sheep.

The optimal rate to rewarm infants after therapeutic hypothermia is unclear. In this study we examined whether slow rewarming after 72 h of hypothermia would attenuate white matter injury. Near-term fetal sheep received sham occlusion (n = 8) or cerebral ischemia for 30 min, followed by normothermia (n = 7) or hypothermia from 3-72 h, with either spontaneous fast rewarming (n = 8) within 1 h, or slow rewarming at ~0.5 °C/h (n = 8) over 10 h. Fetuses were euthanized 7 days later. Ischemia was associated with loss of total and mature oligodendrocytes, reduced expression of myelin proteins and induction of microglia and astrocytes, compared with sham controls (P < 0.05). Both hypothermia protocols were associated with a significant increase in numbers of total and mature oligodendrocytes, area fraction of myelin proteins and reduced numbers of microglia and astrocytes, compared with ischemia-normothermia (P < 0.05). There was no difference in the number of oligodendrocytes, microglia or astrocytes or expression of myelin proteins between fast and slow rewarming after hypothermia. The rate of rewarming after a clinically relevant duration of hypothermia had no apparent effect on white matter protection by hypothermia after cerebral ischemia in near-term fetal sheep. Persistent white matter injury is a major contributor to long-term disability after neonatal encephalopathy despite treatment with therapeutic hypothermia. The optimal rate to rewarm infants after therapeutic hypothermia is unclear; current protocols were developed on a precautionary basis. We now show that slow rewarming at 0.5 °C/h did not improve histological white matter injury compared with rapid spontaneous rewarming after a clinically established duration of hypothermia in near-term fetal sheep.

Cognitive Impairment in Liver Tranplant Recipients: A Cross-Sectional Study.

The proportion of older transplant recipients has increased. Cognitive impairment is not rare after kidney transplant, but data on this issue in liver transplant recipients are scarse. In this cross-sectional study, we evaluated all liver transplant recipients from a single center in Brazil from July 2018 to June 2020 in terms of cognitive performance to determine the prevalence of neurocognitive disorder. We compared liver transplant recipients with neurocognitive disorder with liver transplant recipients without neurocognitive disorder. We also compared those with an alcoholic cause of liver transplant with other patients. The presence of depressive symptoms was assessed. We performed correlations of clinical data with cognitive scores. In a sample of 100 recipients with median age of 62 years (interquartile range, 56.2-69 y), neurocognitive disorder was present in 21% of the group. Patients with cognitive impairment were older (68 y [61-72] vs 61 y [52-68]; P = .019) and had a trend to higher proportion of persistent kidney injury (33.3% vs 13.9%; P = .055) versus patients without cognitive impairment. Recipients with alcoholic cause of liver transplant exhibited worse cognitive performance in the Mini-Mental State Examination (score of 26 [23.7-28.2] vs 28 [26-29]; P = .024) and the Alzheimer Disease Assessment Scale-cognitive (score of 10.4 [8.6-14.2] vs 8 [6.3-10]; P = .008) than other patients. Weak negative correlations were shown in cognitive performance scores versus recipient age (Semantic Verbal Fluency test, r = -0.334 [P = .001]; Clock Drawing test, r = -0.209 [P = .037]; Alzheimer Disease Assessment Scale-cognitive, r = -0.323 [P = .001]). Neurocognitive disorder was common in liver transplant recipients, in part due to increased age. This study also suggested a role for alcoholic cause of liver transplant and persistent kidney injury in the development of cognitive impairment.

Forensic medical determination of the age of fractures based on X-ray research methods: A literature review

Fractures of various locations as a result of traumatism rank second in both Russia and abroad. In Iran, and in the daily work of a forensic expert, skeletal trauma, if not prevalent, is one of the injuries encountered during the examination of victims, accused, and other persons. In addition to determining the mechanism of bone fracture formation, experts face cases of persistent injuries. Determining the time of the occurrence of bodily injuries in living persons generally does not involve special labor if full-fledged research objects are available. A much more difficult task is determining the age of a bone fracture from control radiographs, without primary clinical and radiological data, when the expert is provided with only control radiographs of the area of interest, which were taken after a long time has elapsed from the time of injury. In modern domestic and foreign scientific sources, no clear criteria have been established for determining the age of fractures based radiographs. Although some studies have been devoted to this issue in forensic medical literature, they are based on the results of nonradiological research methods: histological, histochemical, fractographic, ultrasound, and others. In the specialized literature on traumatology, determining the age of fractures since occurrence is not a priority. The analysis of literary sources shows the relevance of research on radiography methods for forensic medical practice.