Long-term Impairment Research Articles

Osteoarticular tuberculosis: imaging findings in pediatric patients.

Osteoarticular tuberculosis (TB) is an uncommon form of extrapulmonary TB that has the potential to damage joints and bones, generating long-term impairment. Mainly, the initial diagnosis of osteoarticular TB relies on clinical findings and imaging. When required, imaging can aim for less invasive tissue or fluid sampling for pathology, microbiology, and molecular biology analysis. Most TB diagnosis tests have variable and frequently poor sensitivities; however, bone biopsy samples have demonstrated a high percentage of culture positivity. Clinical and imaging findings of osteoarticular TB often mimic other processes, such as rheumatoid arthritis or chronic recurrent multifocal osteomyelitis. When the infection affects the growth plates, angular deformities and extremity length discrepancies can arise. Unfortunately, several osteoarticular TB cases are detected late due to the nonspecific nature of clinical symptoms and non-characteristic imaging findings. This article reviews the most common and atypical osteoarticular TB imaging presentations to increase awareness of osteoarticular TB.

Abstract 4127513: Cardiopulmonary long-term effects 6, 18 and 30 months after severe covid-19 infection

Background: SARS-CoV-2 infection affects the cardiopulmonary system in both the acute and long-term phase. This study aimed to comprehensively assess symptoms and potential long-term impairments 6, 18 and 30 months in patients previously hospitalized for severe Covid-19 infection. Methods: This prospective registry included patients hospitalized for PCR-confirmed Covid-19 infection. Approximately 6 months post-discharge, follow-up examination included patient history, clinical examination, echocardiography, electrocardiogram, cardiac magnetic resonance imaging (cMRI), chest computed tomography (CT) scan, pulmonary function test (PFT), six-minute walk test (6MWT) and a comprehensive laboratory panel. Patients with pathologic findings during the first visit underwent a second (at 18 months) and third (at 30 months) follow-up examination. Those without pathologic findings or who refused further medical examinations were contacted via phone to inquire about symptoms. Results: Between July 2020 and April 2022, 200 patients (91% general ward, 9% intensive care unit) were recruited. Due to dropouts, the second visit was conducted in 170 patients, and the third visit in 139 (74 in person, 65 via telephone). Long Covid criteria were fulfilled by 73% at 6 months, 52% at 18 months and 49% at 30 months post-discharge, with fatigue being the most common symptom (Figure 1). Echocardiography at 6 months showed impaired left ventricular function in 15 patients, with normalization in 80% at 18 months and further 66% at 30 months (Figure 2). cMRI revealed pericardial effusions in 28 patients at 6 months, which resolved in 47% at 18 months and in further 60% at 30 months. Signs of peri- or myocarditis were present in 7 patients at 6 months and were resolved in all 4 patients who attended control studies at 18 months. Chest CT scans at 6 months identified post-infectious residues in 41 patients, with full recovery in 20% at 18 months without further normalization after 30 months. The length of in-hospital stay was identified as a significant predictor for persisting Long Covid 6 months after discharge (95% CI: 1.005 - 1.12, p=0.03). Conclusion: While the prevalence of Long Covid decreased over time, a significant symptom burden persisted at 6, 18 and even 30 months after severe Covid-19 infection. Structural and functional abnormalities were less frequent compared to reported symptoms, posing a challenge in substantiating the causes of these symptoms.

Exposure to Sunset Yellow FCF since post-weaning causes hippocampal structural changes and memory impairment in the adult rat: The neuroprotective effects of Coenzyme Q10.

This study aimed to investigate whether exposure to Sunset Yellow FCF (SY) since post-weaning can lead to hippocampal structural changes and memory impairment in adult rat and whether the Coenzyme Q10 (CoQ10) can protect against these adverse effects. The weanling rats were randomly divided into six groups and were treated daily by oral gavage for 6 weeks, as follows: (I) control group, administered distilled water (0.3mL/100 g/day); (II) CoQ10 group, received 10mg/kg/day CoQ10; (III) low SY group, received 2.5mg/kg/day SY; (IV) high SY group, received 70 mg/kg/day SY; (V) low SY + CoQ10 group; and (VI) high SY + CoQ10 group. At the end of the sixth week, the novel object recognition (NOR) test was conducted to evaluate memory. Then, after sacrificing animals, the cerebral hemispheres were removed for stereological study and evaluation of MDA levels. The low and high doses of SY led to significant neuronal loss and a decrease in the volume of the hippocampus (CA1 and DG subregions), as well as increased the MDA level, which was associated with short- and long-term memory impairment. Although, administration of CoQ10 prevented the hippocampal neural loss and volume, and caused a reduction in MDA and improved memory in the low and high SY groups. It seems that CoQ10 could prevent the neuronal loss and hippocampal atrophy caused by post-weaning exposure to SY through preventing oxidative stress, ultimately improving memory impairment in rats.

The Tinetti Balance Test Is an Effective Predictor of Functional Decline in Non-Hospitalized Post-COVID-19 Individuals: A Cross-Sectional Study.

Background/Objectives: Individuals with post-COVID-19 conditions risk developing short- and/or long-term neuromuscular impairments, including postural imbalance. However, there is limited evidence showing whether balance deficits are associated with declines in the functional status in post-COVID-19 individuals. This study examined postural balance in non-hospitalized post-COVID-19 individuals using different assessment tools and tested the most relevant balance tools in predicting functional status. Methods: This cross-sectional study enrolled 60 adults split into control (n = 30) and post-COVID-19 (n = 30) groups. Postural balance was assessed in both groups using the Functional Reach Test (FRT), Berg Balance Scale (BBS), Timed Up and Go (TUG), Tinetti Balance Test (Tinetti), and Mini-BESTest (MBT). Functional status in the post-COVID-19 group was assessed using post-COVID-19 functional status (PCFS). Results: Significant differences in postural stability between groups were found only for the FRT. All balance tests showed a statistically significant correlation with PCFS in the post-COVID-19 group, with better performance in all tests being associated with better functional status: Tinetti (r = -0.584), FRT (r = -0.542), MBT (r = -0.530), BBS (r = -0.415) and TUG (r = 0.368). Tinetti was the independent variable that significantly played an important role in determining PCFS (adjusted R2 = 0.318, p < 0.001). Conclusions: Post-COVID-19 functional status is best determined by the Tinetti Balance Test, making it an effective tool for assessing postural balance deficits in this population, with potential implications for postural control assessment and rehabilitation.

The macrophage migration inhibitory factor/CD74 axis in traumatic spinal cord injury: lessons learned from animal and human studies.

Traumatic spinal cord injury (SCI) is a severe condition leading to long-term impairment of motor, sensory, and autonomic functions. Following the initial injury, a series of additional events is initiated further damaging the spinal cord. During this secondary injury phase, both an inflammatory and immune modulatory response are triggered that have damaging and anti-inflammatory properties, respectively. The proinflammatory cytokine macrophage migration inhibitory factor (MIF) and its receptor CD74 have been extensively studied in traumatic SCI. MIF expression is increased in spinal cord tissue after experimental SCI, mainly in astrocytes and microglia, as well as in the plasma of SCI patients. Functionally, MIF and CD74 were shown to regulate astrocyte viability, proliferation and cholesterol metabolism, microglia migration, and neuronal viability. Moreover, inhibition of the MIF/CD74 axis improved the functional recovery of SCI animals. We provide a detailed overview of studies analyzing the role of MIF and CD74 in traumatic SCI. We describe results from animal studies, using rat and mouse models for SCI, and human studies. Furthermore, we propose a new path for investigation, focused on B cells, that might lead to a better understanding of how MIF and CD74 contribute to the secondary injury cascade following traumatic SCI.

Persistent pulmonary impairment after 2 years of COVID-19 infection: An observational study.

Persistent dyspnoea and pulmonary function impairment are common after coronavirus disease 2019 (COVID-19). However, long-term outcomes beyond 2 years of infection are unknown. In this single-center study, we observed the trend of self-reported dyspnoea and pulmonary functions among subjects attending a post-COVID clinic in India after 2 years of COVID-19 illness. Using logistic regression, we explored the clinico-demographic factors associated with persistent dyspnoea and impaired lung functions beyond 2 years. Among 231 included subjects (68.8% male) with a mean [standard deviation (SD)] age of 44.8 (13.2) years, 119 (51.5%) had recovered from moderate-to-severe COVID-19. The median [inter-quartile range (IQR)] time intervals from COVID-19 diagnosis (T0) to clinical enrolment (T1) and final follow-up (T2) were 3.3 (1.9-5.5) months and 29.5 (27.2-32.2) months, respectively. Between T1 and T2, the prevalence of self-reported dyspnoea remained stable in the whole cohort (39.4% vs. 36.4%, P = 0.26) but declined in the sub-group with moderate-to-severe COVID-19 (63% vs. 54.6%, P = 0.03). Persistent dyspnoea at T2 was associated with female sex (P = 0.007), moderate-to-severe COVID-19 (P < 0.001), and infection during the delta wave (P < 0.001). At T2, impairment in forced vital capacity (FVC) was seen in 48.1% subjects. Persistently impaired FVC was associated with older age (P value = 0.047), female sex (P value <0.001), and infection during the delta wave (P value = 0.02). Persistent self-reported dyspnoea and impaired pulmonary functions were common in COVID-19 survivors beyond 2 years of infection. Female sex and infection during the delta wave were associated with long-term impairments.

LONG-TERM OUTCOMES OF CRITICALLY ILL PATIENTS WITH COVID-19: A SYSTEMATIC REVIEW

BackgroundSurvivors of critical illness are susceptible to long-term functional impairments following admission to an intensive care unit (ICU). In the context of the COVID-19 pandemic, there has been a surge in patients admitted to ICU with severe acute respiratory syndrome coronavirus type 2. The long-term consequences of critical illness due to COVID-19 illness remain unclear. Research QuestionTo determine the long-term outcomes of adult patients admitted to ICU for COVID-19. Study Design and MethodsWe searched Ovid MEDLINE and EMBASE using subject heading and free-text terms related to long-term outcomes of critically ill patients with COVID-19. We included all articles that reported original data on outcomes from 90 days onwards for adult patients admitted to ICU for COVID-19. Data extracted included study details, patient characteristics, outcomes reported, measurement tools used and timing of assessment. ResultsA total of 14,882 studies were screened, from which 134 studies fulfilled the selection criteria. Follow-up timepoints ranged from 90 days to 2 years following critical illness. Post-hospital mortality was the most reported outcome (n=60), with the general ICU cohort having an aggregate mortality rate of 35.5% (95% CI 34.7-36.2) at 90 days and 31.6% (95%CI 30.9-32.4) at 6 months. A plethora of other outcomes were assessed, including psychological function/mental health (n=49), persistent symptoms (n=47), quality of life (n=47), physical function (n=33) and cognitive function (n=31). For each outcome, different measurement tools were employed, making data synthesis across studies difficult. InterpretationImportant evidence gaps remain regarding the long-term health outcomes and healthcare needs for survivors of critical COVID-19 illness. This review found that mortality was the most reported long-term outcome. Significant heterogeneity was evident across studies in terms of outcomes assessed, measurement instruments used and the duration of follow-up. Future research requires increased consistency in outcomes assessed and measurement tools to inform clinical practice.

FGF21 Alleviates Hypoxic-Ischemic White Matter Injury in Neonatal Mice by Mediating Inflammation and Oxidative Stress Through PPAR-γ Signaling Pathway.

White matter injury (WMI), the most common type of brain damage in infants born preterm, is characterized by failure in oligodendrocyte progenitor cell maturation and myelination, thereby contributing to long-term neurological impairments. Regrettably, effective therapies for promoting remyelination and improving function are currently lacking for this growing population affected by WMI. Recombinant human fibroblast growth factor (rhFGF) 21 modulated microglial activation and then ameliorated brain damage and improved neurological deficits in several central nervous system diseases. However, the effects of rhFGF21 treatment on WMI in preterm infants remain uncertain. In this study, we established an in vivo mouse model of cerebral hypoxia-ischemia (HI)-induced brain WMI and an in vitro model using oxygen-glucose deprivation (OGD)-treated HMC3 cells to investigate the neuroprotective effects of rhFGF21 against WMI and elucidated the potential mechanism. Our findings demonstrated that administration of rhFGF21 significantly ameliorated the retardation of oligodendrocyte differentiation, promoted myelination, and mitigated axonal deficits, synaptic loss, and GFAP scarring, thereby improving lifelong cognitive and neurobehavioral dysfunction associated with WMI. Moreover, rhFGF21 modulated microglial polarization, promoted a shift from the M1 to the M2 microglial phenotype, and suppressed microglial activation, thus ameliorating inflammatory response and oxidative stress. Additionally, rhFGF21 treatment significantly inhibited the HMGB1/NF-κB pathway linked to inflammation, and activated the NRF2 pathway associated with oxidative stress through the upregulation of PPAR-γ. Importantly, the beneficial effects of rhFGF21 on HI-induced WMI and microglial activation were dramatically inhibited by PPAR-γ antagonist and its siRNA. Our findings provide compelling evidence that rhFGF21 treatment mitigated the inflammatory response and oxidative stress through the modulation of microglial polarization via the PPAR-γ-mediated HMGB1/NF-κB pathway and the NRF2 pathway, respectively, contributes to neuroprotection and the amelioration of WMI in neonatal mice. Thus, rhFGF21 represents a promising therapeutic agent for the treatment of neonatal WMI.

VP3.15 reduces acute cerebellum damage after germinal matrix-intraventricular hemorrhage of the preterm newborn

Germinal matrix-intraventricular hemorrhage (GM-IVH) is one of the most common complications of the preterm newborn. The pathology of the GM-IVH is not completely understood and even regions distant from the lesion area are severely affected. It has been suggested that cerebellar diaschisis may underlie the neurodevelopmental problems that many of these kids show, including cerebral palsy, attention deficit disorders or hyperactivity. Additionally, GM-IVH has no successful treatment. VP3.15 is a dual action phosphodiesterase 7 (PDE7) and glycogen synthase kinase-3β (GSK-3β) inhibitor that limits neuroinflammation and neuronal loss. Therefore, it might also provide a relevant tool to reduce complications associated with GM-IVH. We have used a murine model of GM-IVH to analyze the short and long-term effects of VP3.15 in brain pathology and behavioral complications. In our hands, the induction of unilateral GM-IVH to P7 CD1 mice results in a short-term (P14) compromise of the cerebellar neuronal population and Purkinje cells arborization, an increase of microglia burden in the nuclei and an overall increase of punctuate cerebellar hemorrhages. Whereas brain alterations are no longer observed in the long term (P110), these animals present overt hyperactivity when analyzed in the adulthood, supporting the long-term behavioral impairment. Also, hyperactivity significantly correlates with ipsi and contralateral cerebellar sizes, neuronal densities and myelin basic protein levels. Importantly, treatment with VP3.15 significantly reduces neuronal loss, Purkinje cells simplification, the presence of cerebellar hemorrhages, as well as hyperactivity. Altogether, our data support the neuroprotective effects of VP3.15 in GM-IVH of the PT.

Literature review: Early-onset Scoliosis and the Space Available for Lung (SAL) post-surgery

Background: Early-onset scoliosis (EOS) poses significant risks to thoracic development and pulmonary function in children due to the deformities’ impact on the space available for lung (SAL). Various surgical techniques, including growth-sparing methods like growing rods, vertical expandable prosthetic titanium ribs (VEPTR), and the Shilla system, aim to correct spinal deformities while allowing for thoracic growth. This literature review explores the efficacy of these interventions in improving SAL and lung function, as measured by forced vital capacity (FVC) and other pulmonary outcomes. Studies indicate that growth-friendly techniques are associated with substantial improvements in SAL, with growing rods showing an average 30% increase in thoracic volume and a corresponding improvement in pulmonary function. VEPTR has been similarly effective in increasing thoracic volume by 25% in patients with thoracic insufficiency syndrome. The Shilla system offers advantages in maintaining spinal correction while promoting growth but has been noted for potential complications like metal debris. Conclusion: Despite these advances, complications such as hardware failure and the need for revision surgeries remain concerns. This review underscores the importance of early surgical intervention to maximize thoracic volume and prevent long-term pulmonary impairment. However, further research is needed to assess the long-term outcomes of these surgical techniques, particularly in adulthood.

Enhanced platelet sensitization is accompanied by increased expression of the transporter MRP4 and elevated plasma S1P levels in mild COVID-19 convalescents

Viral infections can lead to platelet activation and hemostatic complications. However, the extent to which platelet reactivity remains altered after convalescence, contributing to long-term health impairments as observed after COVID-19 is not yet fully understood. Therefore, we conducted a cohort study (DRKS00025217) to determine platelet function in individuals convalesced from mild COVID-19. Assays were performed ex vivo with blood from convalescents at 2–15 weeks and 6–10 months after convalescence, focusing on platelet aggregation, activation markers, and thrombin formation. In addition, two other potentially relevant factors for platelet function were examined: the immunomodulatory mediator sphingosine-1-phosphate (S1P) and the platelet expression of the transporter MRP4 (ABCC4). Our findings indicate that robust platelet functions, including platelet aggregation determined by light transmission aggregometry, and thrombin formation, were not altered in convalescents compared to matched control individuals. However, an elevation in subtle platelet activation markers, such as P-selectin surface expression and activation of glycoprotein IIb/IIIa, was observed 2–15 weeks after convalescence. This was accompanied by an increased expression of MRP4 in platelets and significantly elevated levels of S1P in platelet-poor plasma. Our findings suggest increased platelet sensitization and a pro-inflammatory state even after convalescence from mild COVID-19, pointing toward MRP4 and S1P as associated factors.

Long-term mental health impairments in survivors of critical illness

Abstract Background Survivors of critical illness frequently suffer from long-term disabilities, including physical, cognitive, and mental impairments (post-intensive care syndrome). However, long-term studies are scarce and healthcare services for critical illness survivors are limited, not only in Germany. Therefore, we followed-up on anxiety, depression, and post-traumatic stress disorder (PTSD) during post-intensive care unit (ICU) rehabilitation and up to 1 year after critical illness onset. Methods Patients at Schoen Clinic Bad Aibling in Germany were eligible for this prospective cohort study after receiving ≥5 days of mechanical ventilation. The Hospital Anxiety and Depression Scale (HADS; subcategory score ≥8) was conducted after ICU discharge (V1), at discharge from inpatient rehabilitation (V2) and 1 year after critical illness onset (V3). The Impact of Event Scale-6 (score ≥1.75) was conducted to assess PTSD at V3. Multiple logistic regressions were performed. Results We included 250 patients (62±14 years, 34% female, median stay on ICU 55 days, median duration of rehabilitation 65 days). 10% died before V3. Anxiety decreased during rehabilitation (effect size r = 0.35, p&amp;lt;.001), but increased again until V3 (r = 0.42, p&amp;lt;.001). At V3, 54% suffered from anxiety. Depression also decreased during rehabilitation (r = 0.46, p&amp;lt;.001), and increased again until V3 (r = 0.39, p&amp;lt;.001). At V3, 44% showed depressive symptoms and 38% suffered from PTSD. COVID-19 diagnosis was associated with increased anxiety (p&amp;lt;.001), depression (p=.068), and PTSD at V3 (p=.028), compared to non-COVID-19 patients. Furthermore, longer duration of mechanical ventilation was associated with increased anxiety (p=.041) and depression (p=.019) at V3. Conclusions Mental health impairments frequently occur in critical illness survivors, and they seem to worsen after rehabilitation. As these impairments can significantly impact daily functioning and quality of life, tailored healthcare services are urgently needed. Key messages • Anxiety, depression, and PTSD are frequent in critical illness survivors, even 1 year after critical disease onset. This calls for tailored healthcare services. • Patients with COVID-19 and longer mechanical ventilation suffer from more severe mental health impairments.

A new natural product derived from cyclosorus terminans provides cardiometabolic protection against obese-induced cardiac dysfunction in rats via suppressing mitochondrial dysfunctions and apoptosis

Abstract Background The development of a novel pharmacological target for obesity has long been considered challenging in mitigating the global cardiovascular complications and mortality. Given the cytotoxic effects associated with various anti-obesity drugs, there is growing interest in exploring new natural products as potential sources for bioactive agents to treat obesity-associated diseases with minimal side effects. While Cyclosorus terminans extract has demonstrated anti-diabetic and anti-obese efficacies in adipose-derived stem cells, its cardioprotective effects in high-fat diet (HFD)-induced obese-insulin resistance rat models have never been elucidated. Purpose To examine the effects of long-term Cyclosorus terminans treatment on metabolic, cardiac, and mitochondrial functions and apoptosis in HFD-induced obese-insulin-resistant rat models Methods Male Wistar rats (n=10) were continually fed with HFD and treated with either vehicle (HFV, virgin oil for 2 ml/kg/day, p.o., n=5) or Cyclosorus terminans (HFC, 100 mg/kg/day, p.o., n=5) for 12 weeks. Rats fed a normal diet (NDV, n=5) were used as a control to confirm the development of HFD-induced obesity. The left ventricular ejection fraction (LVEF) and the ratio between early (E) and late atrial (A) ventricular filling velocity were measured using echocardiography, and the homeostatic model assessment for insulin resistance (HOMA-IR) was determined using blood serum. The cardiac tissue was processed to assess mitochondrial reactive oxygen species (ROS) levels, membrane potential (MMP) changes via red/green fluorescence intensity ratio, and apoptotic protein. Results HFV rats became obese and had impaired cardiometabolic function as shown by reducing LVEF, E/A ratio, and increasing HOMA-IR, respectively (Fig. 1A-C). These obese rats also had mitochondrial ROS overproduction, MMP depolarization (reduced red/green ratio), and apoptosis (increased Bax protein expression) (Fig. 1D-F). Treatment with Cyclosorus terminans (HFC) significantly mitigated mitochondrial dysfunction and apoptosis, resulting in cardiometabolic protection in HFD-fed rats (Fig. 1A-F). Conclusion A new natural product derived from Cyclosorus terminans effectively protected the heart against long-term HFD-induced cardiometabolic impairments by reducing mitochondrial dysfunction and apoptosis. These findings demonstrate Cyclosorus terminans as a novel cardiometabolic protection against obesity-related cardiac complications.

External validation of the CA-AKI score in patients with acute coronary syndrome: A real-world cohort analysis from Asia

Abstract Background Contrast-associated acute kidney injury (CA-AKI) is associated with long-term impairment of kidney function, the need for renal replacement therapy, and subsequent all-cause deaths. A practical risk score, the CA-AKI risk score is derived for the prediction of contrast-associated acute kidney injury. However, this novel score has not received sufficient evidence of external validation in real-world studies, especially in Asian individuals. Methods Short-term endpoints and long-term endpoints were assessed in 8,816 patients with acute coronary syndrome enrolled in a large Asia registry. Discrimination was assessed by Harrell’s C statistic, and calibration was assessed by calibration plots. The ability of the CA-AKI score to predict short-term and long-term prognosis was assessed. Results CA-AKI occurred in 5.3% of the patients, with a stepwise increase of CA-AKI rates from the lowest to the highest of the 4 risk categories. When predicting the risk of CA-AKI, both discrimination and calibration were helpful in model 2 (C-index: 0.72; slope: 0.97) and in model 1(C-index: 0.69; slope: 1.02). The risks of 1-year all-cause mortality and 1-year bleeding were higher in CA-AKI patients (HR: 2.70 [95% CI: 2.22-3.30] and HR: 1.76 [95% CI: 1.41-2.46]; respectively). Conclusion The updated CA-AKI risk score could accurately identify patients with contrast-associated acute kidney injury, the occurrence of which is strongly associated with long-term mortality and bleeding.

Cardiopulmonary long-term effects 6, 18 and 30 months after severe COVID-19 infection

Abstract Background SARS-CoV-2 infection affects the cardiopulmonary system in both the acute and long-term phase. This study aimed to comprehensively assess symptoms and potential longterm impairments 6, 18 and 30 months in patients previously hospitalized for severe Covid-19 infection. Methods This prospective registry included patients hospitalized for PCR-confirmed Covid-19 infection. Approximately 6 months post-discharge, follow-up examination included patient history, clinical examination, echocardiography, electrocardiogram, cardiac magnetic resonance imaging (cMRI), chest computed tomography (CT) scan, pulmonary function test (PFT), six-minute walk test (6MWT) and a comprehensive laboratory panel. Patients with pathologic findings during the first visit underwent a second (at 18 months) and third (at 30 months) follow-up examination. Those without pathologic findings or who refused further medical examinations were contacted via phone to inquire about symptoms. Results Between July 2020 and April 2022, 200 patients (91% general ward, 9% intensive care unit) were recruited. Due to dropouts, the second visit was conducted in 170 patients and the third visit in 139 (74 in person, 65 via telephone). Long Covid criteria were fulfilled by 73% at 6 months, 52% at 18 months and 49% at 30 months post-discharge, with fatigue being the most common symptom (Figure 1). Echocardiography at 6 months showed impaired left ventricular function in 15 patients, with normalization in 80% at 18 months and further 66% at 30 months (Figure 2). cMRI revealed pericardial effusions in 28 patients at 6 months, which resolved in 47% at 18 months and in further 60% at 30 months. Signs of peri- or myocarditis were present in 7 patients at 6 months and were resolved in all 4 patients who attended control studies at 18 months. PFT at 6 months detected reduced vital capacity in 17 patients, of whom 10% returned to normal at 18 months and a further 66% showed normalization at 30 months. Chest CT scans at 6 months identified post-infectious residues in 41 patients, with full recovery in 20% at 18 months without further normalization after 30 months. The length of in-hospital stay was identified as a significant predictor for persisting Long Covid 6 months after discharge (95% CI: 1.005 - 1.12, p=0.03). No predictors have been found for Long Covid at 18 and 30 months. Conclusion While the prevalence of Long Covid decreased over time, a significant symptom burden persisted at 6, 18 and even 30 months after severe Covid-19 infection. Structural and functional abnormalities were less frequent compared to reported symptoms, posing a challenge in substantiating the causes of these symptoms.

White matter protection with insulin-like growth factor-1 after hypoxia-ischaemia in preterm foetal sheep.

Perinatal hypoxia-ischaemia in extremely preterm infants is associated with long-term neurodevelopmental impairment, for which there is no specific treatment. Insulin-like growth factor-1 can reduce acute brain injury, but its effects on chronic white matter injury after hypoxia-ischaemia are unclear. Preterm-equivalent foetal sheep (0.6 gestation) received either sham-asphyxia or asphyxia induced by umbilical cord occlusion for 30 min, and recovered for either 3 or 35 days after asphyxia. The 35 day recovery groups received either an intracerebroventricular infusion of insulin-like growth factor-1 (1 µg/24 h) or vehicle, from 3 to 14 days after asphyxia. Asphyxia was associated with ventricular enlargement, and loss of frontal and parietal white matter area (P < 0.05 versus sham-asphyxia). This was associated with reduced area fraction of myelin basic protein and numbers of oligodendrocyte transcription factor 2 and mature, anti-adenomatous polyposis coli-positive oligodendrocytes in periventricular white matter (P < 0.05), with persistent inflammation and caspase-3 activation (P < 0.05). Four of eight foetuses developed cystic lesions in temporal white matter. Prolonged infusion with insulin-like growth factor-1 restored frontal white matter area, improved numbers of oligodendrocyte transcription factor 2-positive and mature, anti-adenomatous polyposis coli-positive oligodendrocytes, with reduced astrogliosis and microgliosis after 35 days recovery (P < 0.05 versus asphyxia). One of four foetuses developed temporal cystic lesions. Functionally, insulin-like growth factor-1-treated foetuses had faster recovery of EEG power, but not spectral edge. Encouragingly, these findings show that delayed, prolonged, insulin-like growth factor-1 treatment can improve functional maturation of periventricular white matter after severe asphyxia in the very immature brain, at least in part by suppressing chronic neural inflammation.

Machine Learning-Based Stroke Prediction: A Critical Analysis

Stroke is a critical public health issue that frequently has long-term impairment and negative effects. Devising innovative methods that enable timely and accurate identification and intervention is crucial. In this regard, machine learning (ML) and deep learning (DL) approaches of artificial intelligence (AI) play a crucial role in reducing the incidence of strokes. This study systematically analyzed articles from 2012 to 2022 using the PRISMA Method. PRISMA is a tool that facilitates researchers' access to an online platform for self-directed learning. The cumulative quantity of articles gathered for ten years reached 1405 from five databases. However, only 79 relevant articles were used for identification. The main objective was to provide a thorough taxonomy that classifies using and implementing machine learning approaches for stroke prediction. The results of this experiment confirm that machine-learning techniques have a great deal of potential for accurate stroke prediction. Nevertheless, challenges such as biased data and algorithms and the need for models that can be adjusted to accommodate various demographics and healthcare systems continue to exist. It is essential to recognize the need for additional research projects that thoroughly explore potential data biases, algorithmic biases, and the generalizability of models across various demographics and healthcare systems. More research is necessary to further the literature on the complete assessment of machine learning models in precisely forecasting stroke occurrences.

Management of Neglected Pediatric Monteggia Fracture-Dislocation: A Case Report and Literature Review

Background: Missed or neglected Monteggia lesions are defined as classical fracture-dislocation presenting at least four weeks after injury. This injury in children is often challenging to treat and requires complex methods to achieve optimal results. Case Report: We report a 6-year-old girl with a 2-month-old neglected Bado type-I Monteggia fracture-dislocation. Our patient underwent ulnar osteotomy, bone grafting, and fixation with a semi-tubular plate along with open radial head reduction. Although the patient experienced wound complications at the bone graft harvest site, she achieved an excellent outcome with restored functionality and range of motion (ROM). Conclusion: Neglected Monteggia injuries in pediatric patients demand multifaceted treatment approaches due to their complexity and potential for long-term functional impairment. The absence of a consensus on definitive treatment underscores the importance of early diagnosis and open reduction to enhance long-term outcomes. This case report highlights the effectiveness of ulnar osteotomy, plate fixation, and open radial head reduction in achieving favorable results.

Persistent Fatigue, Weakness, and Aberrant Muscle Mitochondria in Survivors of Critical COVID-19.

Persistent skeletal muscle dysfunction in survivors of critical illness due to acute respiratory failure is common, but biological data elucidating underlying mechanisms are limited. The objective of this study was to elucidate the prevalence of skeletal muscle weakness and fatigue in survivors of critical illness due to COVID-19 and determine if cellular changes associate with persistent skeletal muscle dysfunction. A prospective observational study in two phases: 1) survivors of critical COVID-19 participating in physical outcome measures while attending an ICU Recovery Clinic at short-term follow-up and 2) a nested cohort of patients performed comprehensive muscle and physical function assessments with a muscle biopsy; data were compared with non-COVID controls. ICU Recovery Clinic and clinical laboratory. Survivors of critical COVID-19 and non-COVID controls. None. One hundred twenty patients with a median of 56 years old (interquartile range [IQR], 42-65 yr old), 43% female, and 33% individuals of underrepresented race attended follow-up 44 ± 17 days after discharge. Patients had a median Acute Physiology and Chronic Health Evaluation-II score of 24.0 (IQR, 16-29) and 98 patients (82%) required mechanical ventilation with a median duration of 14 days (IQR, 9-21 d). At short-term follow-up significant physical dysfunction was observed with 93% of patients reporting generalized fatigue and performing mean 218 ± 151 meters on 6-minute walk test (45% ± 30% of predicted). Eleven patients from this group agreed to participate in long-term assessment and muscle biopsy occurring a mean 267 ± 98 days after discharge. Muscle tissue from COVID exhibited a greater abundance of M2-like macrophages and satellite cells and lower activity of mitochondrial complex II and complex IV compared with controls. Our findings suggest that aberrant repair and altered mitochondrial activity in skeletal muscle associates with long-term impairments in patients surviving an ICU admission for COVID-19.

The Management and Prevention of Delirium in Elderly Patients Hospitalised in Intensive Care Units: A Systematic Review.

Delirium or an acute confusional state (ACS) is characterised as being a frequent and complex hospital complication in older adult patients, which can affect their level of independence and increase patient morbidity and mortality. Critically ill patients in the intensive care unit (ICU) frequently develop ICU delirium, leading to longer hospital and ICU stays, increased mortality and long-term impairment. This review aims to assess existing evidence of interventions that can be considered effective for the management and prevention of delirium in ICUs, reducing short-term morbidity and mortality, ICU and hospital admission times and the occurrence of other long-term complications. For this systematic review, we searched Medline, PubMed, Cochrane Library, CINHAL, LILACS, SciELO and Dialnet from January 2018 to August 2024, in English, Spanish and French. MeSH descriptors were adjusted to search the different databases. We also checked Prospero for ongoing systematic reviews. The electronic search yielded a total of 2656 studies, of which 14 trials met the eligibility criteria, with a total of 14,711 participants. We included eight randomised clinical trial (RCTs), four cohort analyses, one systematic review and one observational trial, including participants over 65 years admitted to the ICU. Ten of these studies were based on pharmacological interventions, three of them examined non-pharmacological interventions and the remaining study examined mixed (pharmacological and non-pharmacological) interventions. Six placebo RCTs were included, plus four reported comparisons between different drugs. Regarding non-pharmacological interventions, nursing programmes focused on optimising modifiable risk factors or the use of therapies such as bright light are emerging. Regarding mixed interventions, we found the combination of invasive techniques and with sedoanalgesia. Due to its satisfactory level of sedation, dexmedetomidine is presented as a viable option because, although olanzapine offers safer results, postoperative administration angiotensin inhibitor systems significantly reduced the incidence of delirium. As for propofol, no significant differences were found. Among the non-pharmacological and mixed therapies, bright light therapy was able to reduce the incidence of delirium, and the combination of epidural/general anaesthesia was effective in all subtypes of delirium. Concerning the remaining interventions, the scientific evidence is still insufficient to provide a definitive recommendation.