Acute Phase Research Articles

Hemodynamics and wall shear metrics in a pulmonary autograft: Comparing a fluid-structure interaction and computational fluid dynamics approach

ObjectiveIn young patients, aortic valve disease is often treated by placement of a pulmonary autograft (PA) which adapts to its new environment through growth and remodeling. To better understand the hemodynamic forces acting on the highly distensible PA in the acute phase after surgery, we developed a fluid-structure interaction (FSI) framework and comprehensively compared hemodynamics and wall shear-stress (WSS) metrics with a computational fluid dynamic (CFD) simulation. MethodsThe FSI framework couples a prestressed non-linear hyperelastic arterial tissue model with a fluid model using the in-house coupling code CoCoNuT. Geometry, material parameters and boundary conditions are based on in-vivo measurements. Hemodynamics, time-averaged WSS (TAWSS), oscillatory shear index (OSI) and topological shear variation index (TSVI) are evaluated qualitatively and quantitatively for 3 different sheeps. ResultsDespite systolic-to-diastolic volumetric changes of the PA in the order of 20 %, the point-by-point correlation of TAWSS and OSI obtained through CFD and FSI remains high (r > 0.9, p < 0.01) for TAWSS and (r > 0.8, p < 0.01) for OSI). Instantaneous WSS divergence patterns qualitatively preserve similarities, but large deformations of the PA leads to a decrease of the correlation between FSI and CFD resolved TSVI (r < 0.7, p < 0.01). Moderate co-localization between FSI and CFD is observed for low thresholds of TAWSS and high thresholds of OSI and TSVI. ConclusionFSI might be warranted if we were to use the TSVI as a mechano-biological driver for growth and remodeling of PA due to varying intra-vascular flow structures and near wall hemodynamics because of the large expansion of the PA.

Multifocal Osteonecrosis in Spinal Cord Injury

Dear Editors, Necrosis of the bone marrow and trabecular portion as a result of limited blood flow is known as osteonecrosis (ON) [1]. Several causes have been proposed for the development of ON, including vascular occlusions, ischemia, intravascular coagulation in interosseous tissue, increased intracortical pressure, mechanical stress, precursor cell death, and suppression of angiogenesis. There are multiple risk factors and medical condition associated with ON, including infections, hematological and coagulation problems, connective tissue illnesses, kidney diseases, excessive alcohol and tobacco use, and the use of corticosteroids and cytotoxic drugs [2]. Multifocal osteonecrosis, defined as the presence of osteonecrosis in three or more bone sites, is a rare entity representing less than 3% of osteonecrosis patients [3]. Due to its potent anti-inflammatory properties, methyl prednisolone (MP), one of the most extensively used corticosteroids, has been used for a long time in the acute phase of spinal cord injury and brain edema due to its strong anti-inflammatory properties [4]. Although studies have reported cases of multifocal osteonecrosis (MFON) brought on by corticosteroid medication, this link has never been examined in a patient with a spinal cord injury. This letter aims to highlight MFON that occurred in a patient who underwent acute spinal cord injury and high-dose steroid therapy.

Disentangling the acute subjective effects of classic psychedelics from their enduring therapeutic properties.

Recent research with classic psychedelics suggests significant therapeutic potential, particularly for neuropsychiatric disorders. A mediating influence behind symptom resolution is thought to be the personal insight - at times, bordering on the mystical - one acquires during the acute phase of a psychedelic session. Indeed, current clinical trials have found strong correlations between the acute subjective effects (ASE) under the influence of psychedelics and their enduring therapeutic properties. However, with potential barriers to widespread clinical implementation, including the healthcare resource-intensive nature of psychedelic sessions and the exclusion of certain at-risk patient groups, there is an active search to determine whether ASE elimination can be accompanied by the retention of persisting therapeutic benefits of these class of compounds. Recognizing the aberrant underlying neural circuitry that characterizes a range of neuropsychiatric disorders, and that classic psychedelics promote neuroplastic changes that may correct abnormal circuitry, investigators are rushing to design and discover compounds with psychoplastogenic, but not hallucinogenic (i.e., ASE), therapeutic potential. These efforts have paved the discovery of 'non-psychedelic/subjective psychedelics', or compounds that lack hallucinogenic activity but with therapeutic efficacy in preclinical models. This review aims to distill the current evidence - both clinical and preclinical - surrounding the question: can the ASE of classic psychedelics be dissociated from their sustained therapeutic properties? Several plausible clinical scenarios are then proposed to offer clarity on and potentially answer this question.

Dietary L-carnitine supplementation modifies blood parameters of mid-lactating dairy cows during standardized lipopolysaccharide-induced inflammation.

L-carnitine, available as feed additive, is essential for the beta-oxidation of free fatty acids in the mitochondrial matrix. It provides energy to immune cells and may positively impact the functionality of leukocytes during the acute phase response, a situation of high energy demand. To test this hypothesis, German Holstein cows were assigned to a control group (CON, n = 26) and an L-carnitine supplemented group (CAR, n = 27, rumen-protected L-carnitine product: 125 g/cow/d, corresponded to total L-carnitine intake: 25 g/cow/d, supplied with concentrate) and received an intravenous bolus injection of lipopolysaccharides (LPS, 0.5 µg/kg body weight, E. coli) on day 111 postpartum as a model of standardized systemic inflammation. Blood samples were collected from day 1 ante injectionem until day 14 post injectionem (pi), with frequent sampling through an indwelling venous catheter from 0.5 h pi to 12 h pi. All parameters of the white blood cell count responded significantly to LPS, while only a few parameters were affected by L-carnitine supplementation. The mean eosinophil count, as well as the percentage of basophils were significantly higher in CAR than in CON over time, which may be due to an increased membrane stability. However, phagocytosis and production of reactive oxygen species by leukocytes remained unchanged following L-carnitine supplementation. In conclusion, although supplementation with 25 g L-carnitine per cow and day resulted in increased proportions of specific leukocyte populations, it had only minor effects on the functional parameters studied in mid-lactating dairy cows during LPS-induced inflammation, and there was no evidence of direct improvement of immune functionality.

Effects of an early intensive blood pressure-lowering strategy using remifentanil and dexmedetomidine in patients with spontaneous intracerebral hemorrhage: a multicenter, prospective, superiority, randomized controlled trial.

Although it has been established that elevated blood pressure and its variability worsen outcomes in spontaneous intracerebral hemorrhage, antihypertensives use during the acute phase still lacks robust evidence. A blood pressure-lowering regimen using remifentanil and dexmedetomidine might be a reasonable therapeutic option given their analgesic and anti-sympathetic effects. The objective of this superiority trial was to validate the efficacy and safety of this blood pressure-lowering strategy that uses remifentanil and dexmedetomidine in patients with acute intracerebral hemorrhage. In this multicenter, prospective, single-blinded, superiority randomized controlled trial, patients with intracerebral hemorrhage and systolic blood pressure (SBP) ≥150 mmHg were randomly allocated to the intervention group (a preset protocol with a standard guideline management using remifentanil and dexmedetomidine) or the control group (standard guideline-based management) to receive blood pressure-lowering treatment. The primary outcome was the SBP control rate (<140 mmHg) at 1 h posttreatment initiation. Secondary outcomes included blood pressure variability, neurologic function and clinical outcomes. A total of 338 patients were allocated to the intervention (n = 167) or control group (n = 171). The SBP control rate at 1 h posttreatment initiation in the intervention group was higher than that in controls (101/161, 62.7% vs. 66/166, 39.8%, difference 23.2%, 95% CI, 12.4 to 34.1%, P < 0.001). Analysis of secondary outcomes indicated that patients in the intervention group could effectively reduce agitation while achieving lighter sedation, but no improvement in clinical outcomes was observed. Regarding safety, the incidence of bradycardia and respiratory depression was higher in the intervention group. Among intracerebral hemorrhage patients with a SBP ≥ 150 mmHg, a preset protocol using a remifentanil and dexmedetomidine-based standard guideline management significantly increased the SBP control rate at 1 h posttreatment compared with the standard guideline-based management. (ClinicalTrials.gov number: NCT03207100, Registration date: June 30, 2017).

Cognitive Impairment and Fatigue in Intensive Care Patients Three Months after the Acute Phase of COVID-19 Infection: Follow-Up with Focus on Differences between the First and Later Waves of the Pandemic

Cognitive Impairment and Fatigue in Intensive Care Patients Three Months after the Acute Phase of COVID-19 Infection: Follow-Up with Focus on Differences between the First and Later Waves of the Pandemic

Cell-free DNA in patients with sepsis: long term trajectory and association with 28-day mortality and sepsis-associated acute kidney injury.

Outcome-prediction in patients with sepsis is challenging and currently relies on the serial measurement of many parameters. Standard diagnostic tools, such as serum creatinine (SCr), lack sensitivity and specificity for acute kidney injury (AKI). Circulating cell-free DNA (cfDNA), which can be obtained from liquid biopsies, can potentially contribute to the quantification of tissue damage and the prediction of sepsis mortality and sepsis-associated AKI (SA-AKI). We investigated the clinical significance of cfDNA levels as a predictor of 28-day mortality, the occurrence of SA-AKI and the initiation of renal replacement therapy (RRT) in patients with sepsis. Furthermore, we investigated the long-term course of cfDNA levels in sepsis survivors at 6 and 12 months after sepsis onset. Specifically, we measured mitochondrial DNA (mitochondrially encoded NADH-ubiquinone oxidoreductase chain 1, mt-ND1, and mitochondrially encoded cytochrome C oxidase subunit III, mt-CO3) and nuclear DNA (nuclear ribosomal protein S18, n-Rps18) in 81 healthy controls and all available samples of 150 intensive care unit patients with sepsis obtained at 3 ± 1 days, 7 ± 1 days, 6 ± 2 months and 12 ± 2 months after sepsis onset. Our analysis revealed that, at day 3, patients with sepsis had elevated levels of cfDNA (mt-ND1, and n-Rps18, all p<0.001) which decreased after the acute phase of sepsis. 28-day non-survivors of sepsis (16%) had higher levels of cfDNA (all p<0.05) compared with 28-day survivors (84%). Patients with SA-AKI had higher levels of cfDNA compared to patients without AKI (all p<0.05). Cell-free DNA was also significantly increased in patients requiring RRT (all p<0.05). All parameters improved the AUC for SCr in predicting RRT (AUC=0.88) as well as APACHE II in predicting mortality (AUC=0.86). In summary, cfDNA could potentially improve risk prediction models for mortality, SA-AKI and RRT in patients with sepsis. The predictive value of cfDNA, even with a single measurement at the onset of sepsis, could offer a significant advantage over conventional diagnostic methods that require repeated measurements or a baseline value for risk assessment. Considering that our data show that cfDNA levels decrease after the first insult, future studies could investigate cfDNA as a "memoryless" marker and thus bring further innovation to the complex field of SA-AKI diagnostics.

Effect of drug therapies on self‐reported chemosensory outcomes after COVID‐19

AbstractObjectiveThe aim of this study was to assess the relative efficacy of medications used following severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infection on self‐reported alterations in taste and/or smell function.MethodsSeven hundred and fourteen persons with self‐reported postcoronavirus disease 2019 (post‐COVID‐19) chemosensory disorders were personally interviewed regarding specific medications they were administered following the acute phase of the disease. The dependent measure—self‐reported total recovery of chemosensory symptoms—was subjected to stepwise logistic regression. Independent predictors included demographic and clinical variables, in addition to specific medications used to mitigate disease symptoms (i.e., systemic corticosteroids, oseltamivir, vitamin C, ibuprofen, hydroxychloroquine, azithromycin, ivermectin, nitazoxanide, anticoagulants, and zinc).ResultsThe median time between COVID‐19 symptom onset and the interviews was 81 days (interquartile range: 60–104). Of the 714 subjects, 249 (34.9%) reported total recovery of their chemosensory function; 437 (61.2%) had at least one treatment since the beginning of the disease. Women and those with more comorbidities had undergone more treatments. The recovery rates of the treated and nontreated groups did not differ significantly. Nonetheless, respondents who had used nitazoxanide tended to have a higher rate of self‐reported taste or smell recovery. Those who took oral zinc were less likely to improve.ConclusionsNo medication employed during the first months after SARS‐CoV‐2 infection had a clear positive effect on returning self‐reported smell or taste function to normal, although nitrazoxide trended in a positive direction. Oral zinc had a negative effect on the reported recovery of these senses.

Current approach to diagnosing and treating necrotizing fasciitis

Introduction: Necrotizing fasciitis is an infrequent yet highly fatal bacterial infection characterized by widespread necrosis of fascia and subcutaneous fat tissue. Though initial symptoms resemble typical infection, necrotizing fasciitis progresses rapidly triggering acute phase response. Individuals with advanced age, chronically ill, immunocompromised, or abusing alcohol are especially susceptible to developing necrotizing fasciitis. In order to reduce mortality, early diagnosis and appropriate treatment are indispensable. Aim of the Study: Aim of this study is through evaluating existing literature to outline the contemporary diagnostic strategies and emerging therapy options for necrotizing fasciitis. Description of the State of Knowledge: Primary diagnostic methods involve clinical evaluation and surgical exploration, complemented by fresh frozen sections for rapid diagnosis and the finger test. Diagnostic imaging incorporates the use of magnetic resonance imaging, computed tomography and ultrasound. The treatment is mostly centered around surgical debridement and antibiotic therapy. Therapies that display potential efficacy include low-dose radiotherapy, hyperbaric oxygen therapy, and the use of intact fish skin grafts for tissue reconstruction after successful treatment. The emerging approach includes therapy targeting systemic inflammatory response syndrome, sepsis induced coagulopathy and critical illness related corticosteroid insufficiency. Conclusions: The management of necrotizing fasciitis primarily depends on traditional methods. Fast identification and proper treatment are pivotal in reducing the mortality rate. Recognizing the significance of addressing the acute phase response in necrotizing fasciitis treatment introduces new possibilities for therapeutic interventions. Further research is vital to evaluate the existing approaches to necrotizing fasciitis management and explore new diagnoistic and therapeutic alternatives.

Construction and validation of clinical prediction model of acupuncture and moxibustion for Bell's palsy

To establish and validate a clinical prediction model of acupuncture and moxibustion for Bell's palsy so as to provide a tool for predicting the effect of acupuncture and moxibustion on Bell's palsy. A total of 269 patients with Bell's palsy were collected from department of acupuncture, moxibustion and tuina, Shengli Oilfield Central Hospital, neurology department, Shenxian County Central Hospital and department of rehabilitation medicine, Dongying Municipal Hospital of TCM from June 2018 to June 2023. All of these cases were treated with acupuncture and moxibustion. Of them, 182 cases, from department of acupuncture, moxibustion and tuina, Shengli Oilfield Central Hospital and neurology department, Shenxian County Central Hospital, were randomized into a training group (128 cases) and an internal validation group (54 cases); 87 cases from department of rehabilitation medicine, Dongying Municipal Hospital of TCM were assigned to an external validation group. The clinical data of all of the cases were extracted from the electronic medical record information platform. Using SPSS25.0 and R4.2.3, through univariate and multivariate Logistic regression analysis, the independent factors influencing the effects of acupuncture and moxibustion on Bell's palsy were identified. By means of internal and external validations, the receiver operating characteristic curve (ROC), the goodness-of-fit curve (GFC) and the decision curve analysis (DCA) were plotted. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of the model were calculated; and its comprehensive performance was evaluated. The results of the multivariate Logistic regression analysis showed that the independent factors for the unsatisfactory effect on Bell's palsy were advanced age, severe symptoms before treatment, no use of steroids within 72 h of onset, and lack of acupuncture-moxibustion therapy during the acute phase or single acupuncture-moxibustion protocol (P<0.05, P<0.01). Based on these factors, nomogram model and online columnar plot prediction tool (https://bmuchen.shinyapps.io/dynnomapp/) were established. The area under the ROC curve of the model was 0.921 (95% CI: 0.877, 0.966), 0.876 (95% CI: 0.787, 0.966), and 0.846 (95% CI: 0.766, 0.926) in the training group, the internal validation group, and the external validation group, respectively, indicating good predictive value. The model showed a satisfactory calibration curve alignment. The decision threshold in the range of 0 to 0.8 provided clinical benefits for participants. The model exhibited the sensitivity from 65.9% to 88.0%, the specificity ranging from 77.3% to 90.7%, the accuracy from 77.8% to 85.9%, the positive predictive value from 83.3% to 90.1%, and the negative predictive value from 70.8% to 78.7%. The comprehensive evaluation indicated a satisfactory clinical application value of the model. The clinical prediction model of acupuncture and moxibustion for Bell's palsy is valuable in its practice and promotion to a certain extent. The predicted results are conductive to clinicians' judgement of the effect of acupuncture and moxibustion for this disease and making effective and high-quality clinical decisions, as well as formulating the optimal therapeutic regimen.

Combined transcriptomics and proteomics unveil the impact of vitamin C in modulating specific protein abundance in the mouse liver

BackgroundVitamin C (ascorbate) is a water-soluble antioxidant and an important cofactor for various biosynthetic and regulatory enzymes. Mice can synthesize vitamin C thanks to the key enzyme gulonolactone oxidase (Gulo) unlike humans. In the current investigation, we used Gulo−/− mice, which cannot synthesize their own ascorbate to determine the impact of this vitamin on both the transcriptomics and proteomics profiles in the whole liver. The study included Gulo−/− mouse groups treated with either sub-optimal or optimal ascorbate concentrations in drinking water. Liver tissues of females and males were collected at the age of four months and divided for transcriptomics and proteomics analysis. Immunoblotting, quantitative RT-PCR, and polysome profiling experiments were also conducted to complement our combined omics studies.ResultsPrincipal component analyses revealed distinctive differences in the mRNA and protein profiles as a function of sex between all the mouse cohorts. Despite such sexual dimorphism, Spearman analyses of transcriptomics data from females and males revealed correlations of hepatic ascorbate levels with transcripts encoding a wide array of biological processes involved in glucose and lipid metabolisms as well as in the acute-phase immune response. Moreover, integration of the proteomics data showed that ascorbate modulates the abundance of various enzymes involved in lipid, xenobiotic, organic acid, acetyl-CoA, and steroid metabolism mainly at the transcriptional level, especially in females. However, several proteins of the mitochondrial complex III significantly correlated with ascorbate concentrations in both males and females unlike their corresponding transcripts. Finally, poly(ribo)some profiling did not reveal significant enrichment difference for these mitochondrial complex III mRNAs between Gulo−/− mice treated with sub-optimal and optimal ascorbate levels.ConclusionsThus, the abundance of several subunits of the mitochondrial complex III are regulated by ascorbate at the post-transcriptional levels. Our extensive omics analyses provide a novel resource of altered gene expression patterns at the transcriptional and post-transcriptional levels under ascorbate deficiency.

Mapping dynamic molecular changes in hippocampal subregions after traumatic brain injury through spatial proteomics

BackgroundTraumatic brain injury (TBI) often results in diverse molecular responses, challenging traditional proteomic studies that measure average changes at tissue levels and fail to capture the complexity and heterogeneity of the affected tissues. Spatial proteomics offers a solution by providing insights into sub-region-specific alterations within tissues. This study focuses on the hippocampal sub-regions, analyzing proteomic expression profiles in mice at the acute (1 day) and subacute (7 days) phases of post-TBI to understand subregion-specific vulnerabilities and long-term consequences.MethodsThree mice brains were collected from each group, including Sham, 1-day post-TBI and 7-day post-TBI. Hippocampal subregions were extracted using Laser Microdissection (LMD) and subsequently analyzed by label-free quantitative proteomics.ResultsThe spatial analysis reveals region-specific protein abundance changes, highlighting the elevation of FN1, LGALS3BP, HP, and MUG-1 in the stratum moleculare (SM), suggesting potential immune cell enrichment post-TBI. Notably, established markers of chronic traumatic encephalopathy, IGHM and B2M, exhibit specific upregulation in the dentate gyrus bottom (DG2) independent of direct mechanical injury. Metabolic pathway analysis identifies disturbances in glucose and lipid metabolism, coupled with activated cholesterol synthesis pathways enriched in SM at 7-Day post-TBI and subsequently in deeper DG1 and DG2 suggesting a role in neurogenesis and the onset of recovery. Coordinated activation of neuroglia and microtubule dynamics in DG2 suggest recovery mechanisms in less affected regions. Cluster analysis revealed spatial variations post-TBI, indicative of dysregulated neuronal plasticity and neurogenesis and further predisposition to neurological disorders. TBI-induced protein upregulation (MUG-1, PZP, GFAP, TJP, STAT-1, and CD44) across hippocampal sub-regions indicates shared molecular responses and links to neurological disorders. Spatial variations were demonstrated by proteins dysregulated in both or either of the time-points exclusively in each subregion (ELAVL2, CLIC1 in PL, CD44 and MUG-1 in SM, and SHOC2, LGALS3 in DG).ConclusionsUtilizing advanced spatial proteomics techniques, the study unveils the dynamic molecular responses in distinct hippocampal subregions post-TBI. It uncovers region-specific vulnerabilities and dysregulated neuronal processes, and potential recovery-related pathways that contribute to our understanding of TBI’s neurological consequences and provides valuable insights for biomarker discovery and therapeutic targets.

Визначення білків гострої фази в крові щурів після імплантації поліпропіленових хірургічних сіток із покриттям на основі танталу та його похідних

At present, more than 30 types of polypropylene surgical meshes are available in the world, but the statistics regarding the secondary inflammatory process after implantation still remain disappointing. Since polypropylene surgical meshes do not decompose well in the body, they can stimulate the surrounding tissuesto develop an inflammatory process that causes adhesions. For the past 50 years, tantalum has been successfully used to produce biocompatible medical implants in surgery, orthopedics, and dentistry. Its excellent anti-inflammatory and antibacterial properties have been repeatedly noted, indicating the possibility of its use as a coating for mesh implants. In order to better predict the outcome after implantation of biomedical materials, it is important to determine the content of acute phase proteins, namely C-reactive protein, haptoglobin and ceruloplasmin. The aim of the study is to determine the content of acute phase proteins, namely C-reactive protein, haptoglobin and ceruloplasmin in the blood of rats after implantation of surgical meshes coated on the basis of tantalum, tantalum oxide and tantalum nitride. Materials and methods. The experimental group included 40 male rats of the WAG population. With the help of surgical intervention, a polypropylene surgical mesh measuring 15x15 mm was implanted between the abdominal wall and various sections of the colon. 28 days after surgery, the experimental animals were decapitated by cervical dislocation. Blood samples were used to determine the content of C-reactive protein, the content of haptoglobin and the content of ceruloplasmin. Results and discussion. The content of C-reactive protein in the blood of rats was statistically 260 % higher in the experimental group implanted with uncoated surgical mesh and 228.8 % higher in the experimental group implanted with polypropylene surgical mesh with tantalum nitride coating in compared with the results in the group of intact animals. Haptoglobin content was statistically 110.5 % higher and ceruloplasmin was statistically 52.6 % higher in the uncoated surgical mesh group compared to the results of the intact animal group. We obtained similar results in the experimental group, which was implanted with a polypropylene surgical mesh with a coating based on tantalum nitride. The content of haptoglobin was 130 % higher and the content of ceruloplasmin was 50.6 % higher statistically compared to the results of the group of intact animals. The C-reactive protein content was 113.3 % and 95.5 % higher, respectively, in the groups implanted with polypropylene surgical meshes with a coating based on tantalum and tantalum oxide compared to the results in the group of intact animals. The content of haptoglobin in the tantalum-based coating group was 83.8 % higher and the content of ceruloplasmin was 32.6 % higher compared to the results obtained in the group of intact animals. In the tantalum oxide- based group, the haptoglobin content was 60.1 % higher and the ceruloplasmin content was 29.3 % higher compared to the results obtained in the intact animal group. Conclusion. Based on the results of the study, it was established that polypropylene surgical meshes coated with tantalum and tantalum oxide significantly reduce the inflammatory reaction compared to uncoated meshes and meshes coated with tantalum nitride. This is supported by lower levels of key inflammatory markers, indicating improved biocompatibility and anti-inflammatory effects of tantalum and tantalum oxide coatings.

Safety and Efficacy of Levetiracetam for Prevention of Epileptic Seizures in Acute Phase of Intracerebral Bleeding

Background: Epilepsy, characterized by recurrent, unprovoked seizures due to anomalous brain activity, is a significant complication for patients with intracerebral hemorrhage (ICH). The onset of epileptic convulsions during the acute phase of ICH can worsen the patient's prognosis and survival chances, making it crucial to identify a safe and effective method to prevent these seizures. Levetiracetam, a pyrrolidone derivative, is noted for its unique mechanism of action, exceptional tolerability, and advantageous pharmacokinetics, making it efficacious against various types of seizures. Objective: This study aims to evaluate the safety and efficacy of levetiracetam in preventing epileptic seizures during the acute phase of ICH and to determine its impact on neurological outcomes in this patient population. Methods: A cross-sectional investigation was conducted between October 2022 and June 2023 at Pak Emirates Military Hospital in Rawalpindi, Pakistan, involving 85 patients with spontaneous ICH confirmed by CT or MRI within 24 hours of symptom onset. Inclusion criteria included adult patients aged 18 or older, with various forms of ICH, excluding isolated subarachnoid hemorrhage, penetrating wound injury, depressed skull fracture, or early posttraumatic seizure. Patients with a Glasgow Coma Scale (GCS) score of less than 6, serum creatinine level &gt;1.7 mg/dL, history of psychosis, unprovoked seizures, cerebrovascular accidents, traumatic brain injuries, or encephalitis within the previous three years were excluded. Patients were administered an initial loading dose of levetiracetam (1,000 to 1,500 mg), followed by a maintenance dose (500 to 1,500 mg every 12 hours) based on renal function. Continuous electroencephalography (cEEG) monitoring was used to detect seizures for at least the first 72 hours of hospital admission. The primary outcome was the incidence of epileptic seizures during hospitalization, while the secondary outcome was the patient's neurological status at discharge, assessed using the Modified Rankin Scale (mRS). Data were analyzed using descriptive statistics and the Chi-square test, with a p-value of ≤0.05 considered statistically significant. Analyses were conducted using SPSS version 25. Results: The mean age of the patients was 47.89 years (SD=7.46), with 62.35% male and 37.65% female. The mean GCS score at admission was 10.52 (SD=2.13), and the mean volume of ICH was 17.5 ml (SD=3.4). At baseline, 2.35% of patients had GCS scores of 3-5, which improved to 0% after treatment. The percentage of patients with GCS scores of 13-15 increased from 65.88% to 83.52% (p=0.3730). Seizures within the first 7 days occurred in 10.58% of patients, and the overall seizure incidence during hospitalization was 20%. At discharge, 9.41% of patients had an mRS score of 0, and the percentage of patients with an mRS score of 2 increased significantly from 18.18% to 37.64% (p=0.4086*). The percentage of patients with severe disability (mRS score of 5) significantly decreased from 22.72% to 5.68% (p=0.0094*). Conclusion: Levetiracetam is effective in improving neurological outcomes and reducing the incidence of seizures in patients with acute intracerebral hemorrhage, with a manageable safety profile. These findings suggest that levetiracetam can be a valuable addition to therapeutic strategies for managing ICH-related seizures, potentially enhancing patient care and improving health outcomes.

Stabilized oral lichen planus does not compromise dental implants survival: A systematic review and meta-analysis.

This study aimed to evaluate the incidence of implant failure in patients with oral lichen planus (OLP) and investigate the potential association between OLP and peri-implant diseases. Embase, Web of Science, PubMed, and Scopus databases were searched for studies with no time restrictions. Meta-analysis was performed calculating pooled proportion of peri-implantitis (PI), peri-implant mucositis (PIM), and bleeding on probing (BOP) prevalence using fixed-effects model. Odds ratio and corresponding 95% CI were calculated to assess the potential risk of PI, PIM, and BOP in dental implant patients with OLP compared to healthy controls. Implant failure rate was 4.38% at the patient level and 4.37% at the implant level. Six patients (3.92%) from five studies were diagnosed with oral cancer after receiving implant. The prevalence of PI, PIM, and BOP at the implant level were 14.00%, 20.00%, and 40.00%, respectively. There was no significant difference in the occurrence of PI and PIM between OLP patients and healthy controls. Stabilized OLP is not considered a significant risk factor for peri-implant diseases. It is advised against placing implants or prostheses during the acute phase of the disease. Histopathological investigation to differentiate OLP from oral lichenoid dysplasia is crucial.

Features and outcomes of focal intimal disruption in acute type B intramural hematoma.

Focal intimal disruption is a risk factor for adverse aorta-related events in acute type B intramural haematoma patients. This study evaluated the impact of focal intimal disruption on overall survival with a selective intervention strategy for large or growing focal intimal disruptions. Additionally, this study evaluated the risk factors associated with the growth of focal intimal disruption. This retrospective study included all consecutive patients admitted for acute type B intramural haematoma between November 2004 and April 2021. The primary outcome was overall survival. The secondary outcome was cumulative incidence of composite aortic events and the growth of focal intimal disruption. The latter was calculated on centerline-reconstructed computed tomography images. A total of 105 patients were included. A total of 106 focal intimal disruptions were identified in 73 patients (73/105, 69.5%). The 1- and 5-year cumulative incidence rates of composite aortic events were 36.2% and 39.2%, respectively. The 1- and 5-year overall survival were 93.3% and 81.5%, respectively. Initial maximal aortic diameter and large focal intimal disruption during acute phase were significant risk factors for composite aortic event, but not risk factors for overall survival. Early appearance interval of focal intimal disruption was a significant risk factor for growth of focal intimal disruption. With a selective intervention strategy for large or growing focal intimal disruptions, the presence of large focal intimal disruption during acute phase does not affect overall survival. Early appearance interval was associated with the growth of focal intimal disruption.

Single-Joint Type Hybrid Assistive Limb for Knee Training in the Acute Postoperative Phase After Opening Wedge High Tibial Osteotomy: A Feasibility and Safety Trial

Single-Joint Type Hybrid Assistive Limb for Knee Training in the Acute Postoperative Phase After Opening Wedge High Tibial Osteotomy: A Feasibility and Safety Trial

Assisted Versus Unassisted Domiciliary Alcohol Detoxification: A Randomized Controlled Trial

Background: Detoxification stands as a crucial phase in the treatment of alcohol use disorders (AUD), yet only limited data is available on the outcomes of home-based detoxification. Assisted domiciliary detoxification involves monitoring an individual’s withdrawal progress, while offering psychosocial support and detoxification services in the comfort of their home. Aim: To study outcomes of assisted over routine domiciliary alcohol detoxification in randomized controlled trials. Methodology: 100 consenting male patients who were advised of domiciliary detoxification were randomized into intervention ( n = 49) and control ( n = 51) groups. A predesigned semi-structured questionnaire was used to assess the socio-demographic and drinking-related variables. Both groups received routine care for alcohol withdrawal from respective treating doctors. Additionally, the intervention group received two sessions of brief intervention for alcohol and daily phone call assistance. Records were kept for adverse events. Phone calls were discontinued once detoxification was completed. Outcomes were measured for successful completion of detoxification and abstention from alcohol at the end of one month. Results: The intervention group had significantly higher successful detoxification rates (85.7% vs. 62.7%, p = .008) and significantly higher abstinence days at the end of one month compared to the control group (22 vs. 10 days, p &lt; .001) with an effect size of 1.2 (confidence interval (CI) 0.69–1.53). Conclusion: This study demonstrates that receiving assistance in the acute phase of domiciliary detoxification helps in a successful detoxification and achieving a significant level of abstinence at the end of one month compared to the control group.

Neutrophils Expressing Programmed Death-Ligand 1 Play an Indispensable Role in Effective Bacterial Elimination and Resolving Inflammation in Methicillin-Resistant Staphylococcus aureus Infection.

Programmed death ligand 1 (PD-L1) is a co-inhibitory molecule expressed on the surface of various cell types and known for its suppressive effect on T cells through its interaction with PD-1. Neutrophils also express PD-L1, and its expression is elevated in specific situations; however, the immunobiological role of PD-L1+ neutrophils has not been fully characterized. Here, we report that PD-L1-expressing neutrophils increased in methicillin-resistant Staphylococcus aureus (MRSA) infection are highly functional in bacterial elimination and supporting inflammatory resolution. The frequency of PD-L1+ neutrophils was dramatically increased in MRSA-infected mice, and this population exhibited enhanced activity in bacterial elimination compared to PD-L1- neutrophils. The administration of PD-L1 monoclonal antibody did not impair PD-L1+ neutrophil function, suggesting that PD-L1 expression itself does not influence neutrophil activity. However, PD-1/PD-L1 blockade significantly delayed liver inflammation resolution in MRSA-infected mice, as indicated by their increased plasma alanine transaminase (ALT) levels and frequencies of inflammatory leukocytes in the liver, implying that neutrophil PD-L1 suppresses the inflammatory response of these cells during the acute phase of MRSA infection. Our results reveal that elevated PD-L1 expression can be a marker for the enhanced anti-bacterial function of neutrophils. Moreover, PD-L1+ neutrophils are an indispensable population attenuating inflammatory leukocyte activities, assisting in a smooth transition into the resolution phase in MRSA infection.

First episode of febrile urinary tractinfection in children, detection and risk factors of kidney scarring: Aprospective cohort study.

This prospective study aimed to evaluate the characteristics and findings of children who presented with acute pyelonephritis (APN) and to determine the independent risk factors for kidney scarring. Patients who satisfied the following criteria were enrolled in the study: first known episode of APN; at least two of the following findings: fever ≥ 38.5 °C, white blood cell count ≥ 10,000/mm3, erythrocyte sedimentation rate ≥ 20 mm/h, C-reactive protein ≥ 20 mg/dL; absence of congenital abnormalities or other kidney and systemic diseases, except vesicoureteral reflux (VUR); no APN relapses until the time of kidney scar detection. 99mTc-Dimercaptosuccinic acid kidney scintigraphy (99mTc-DMSA) was performed at admission, along with a kidney ultrasound. Follow-up 99mTc-DMSA took place after 6 months. Radiographic cystourethrography for VUR detection and grading was performed 1 month after the acute infection. We enrolled 70 children in the study. The kidney ultrasound failed to diagnose more than half of the cases of APN. VUR was found in 21.5% of children. 75% had findings of APN in the acute phase through 99mTc-DMSA, while in the second 99mTc-DMSA, there was a complete remission in 68% of them. Scars were observed more frequently in older children, children with VUR grade ≥ III, and children not on antibiotic prophylaxis. VUR did not appear to be associated with the first episode of APN, and children older than 1 year of age had a higher risk of scarring. Antibiotic prophylaxis may prevent kidney scarring due to host immunomodulatory effects, but more studies are needed so that conclusions can be drawn.