Patients In Acute Stage Research Articles

Characteristics of patients with schizophrenia switching from oral antipsychotics to once-monthly paliperidone palmitate (PP1M): a systematic review

BackgroundThe utilization of once-monthly paliperidone palmitate (PP1M) in schizophrenia treatment has increased due to its enhanced adherence and convenience. However, there is limited evidence on patient characteristics that may influence treatment outcomes when switching from oral antipsychotics (OAPs) to PP1M therapy. This systematic review aims to identify such patient characteristics and explore potential beneficial factors to aid healthcare professionals in clinical practice.MethodsA systematic literature search was conducted in the PubMed, Embase, and Cochrane Library databases up to July 19, 2022. Studies related to patients with schizophrenia who had been previously treated with OAPs and switched to PP1M were identified and included. Outcomes included the Positive and Negative Syndrome Scale (PANSS) total score, the clinical Global Impressions – Severity (CGI-S) score, the Personal and Social Performance (PSP) total score, and hospitalisation rate. Data were independently extracted and analysed. The results were presented through a narrative synthesis.ResultsEleven studies with a total of 4150 patients were included, identifying nine potential characteristics. The most commonly reported characteristics was patient’s prior treatment with OAPs, followed by the stage of disease, duration of illness (DI), ethnicity, reason for switching to PP1M, history of hospitalisation, time of start injection of PP1M, the PANSS and PSP total score at baseline. Patients in the acute stage, with a shorter DI, a less than 1-week time interval to PP1M injection, and a lower PANSS total score at baseline may have a trend on providing better improvements on PANSS total score. Acute stage and shorter DI also showed potential trends in reducing CGI-S score. Early initiation of PP1M, switching for reasons other than lack of efficacy, and a higher PSP score at baseline exhibited potential trends towards better PSP total score improvements.ConclusionOur findings may suggest that patients in acute stage, with a shorter duration of illness, with early initiation of PP1M injection, and lower PANSS or PSP scores may trend towards better clinical results when transitioning to PP1M from OAPs. Further research is necessary to validate these potential associations and identify any unexplored characteristics. Such investigations are crucial for providing comprehensive clinical recommendations and informing treatment strategies in this context.

Effects of repetitive transcranial magnetic stimulation on lower extremity motor function and optimal parameters in stroke patients with different stages of stroke: a systematic evaluation and meta-analysis.

Repetitive transcranial magnetic stimulation (rTMS), as an emerging non-invasive neuromodulation technique, is now widely employed in rehabilitation therapy. The purpose of this paper is to comprehensively summarize existing evidence regarding rTMS intervention for lower limb motor function in patients at different stages of stroke. A systematic search was conducted to identify randomized controlled trials (RCTs) assessing the efficacy of rTMS for treating lower limb motor dysfunction after stroke. Multiple databases, including China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, VIP Database, PubMed, Embase, Web of Science, and Cochrane Library, were searched. The search period extended from the inception of the libraries to June 2024. Literature information was extracted, and methodological quality was evaluated using the risk of bias assessment tool in the Cochrane Handbook. Meta-analysis was performed using Stata 17.0 software. Overall, 49 appropriate studies (including 3,558 stroke subjects) were found. Meta-analysis results demonstrated that rTMS effectively improved lower limb motor function across all stages of stroke. The intervention was particularly more effective in patients in the subacute stage than in the acute or chronic stages. Subgroup analysis revealed that, for acute-stage patients, low-frequency stimulation targeting the M1 or DLPFC brain regions on the unaffected side with 20-40 sessions significantly improved FMA-LE scores. In subacute-phase patients, low-frequency stimulation targeting the M1 brain regions on the unaffected side with 18 sessions significantly improved FMA-LE scores. The results demonstrated that HF-rTMS was more effective than LF-rTMS in improving walking speed, with the greatest efficacy observed at 20 sessions. While for enhancing gait balance in stroke patients, LF-rTMS with the best therapeutic effect was observed at a frequency of 20-40 treatments. This study demonstrates the efficacy of rTMS in improving lower limb motor function, balance, and walking speed in stroke patients at various stages. The findings provide a valuable reference for the development of optimized rTMS treatment plans in clinical practice.Systematic review registration: PROSPERO: CRD42023466094.

Serum biomarkers and disease progression in CT-negative mild traumatic brain injury.

Blood proteins are emerging as potential biomarkers for mild traumatic brain injury (mTBI). Molecular pathology of mTBI underscores the critical roles of neuronal injury, neuroinflammation, and vascular health in disease progression. However, the temporal profile of blood biomarkers associated with the aforementioned molecular pathology after CT-negative mTBI, their diagnostic and prognostic potential, and their utility in monitoring white matter integrity and progressive brain atrophy remain unclear. Thus, we investigated serum biomarkers and neuroimaging in a longitudinal cohort, including 103 CT-negative mTBI patients and 66 matched healthy controls (HCs). Angiogenic biomarker vascular endothelial growth factor (VEGF) exhibited the highest area under the curve of 0.88 in identifying patients from HCs. Inflammatory biomarker interleukin-1β and neuronal cell body injury biomarker ubiquitin carboxyl-terminal hydrolase L1 were elevated in acute-stage patients and associated with deterioration of cognitive function from acute-stage to 6-12mo post-injury period. Notably, axonal injury biomarker neurofilament light (NfL) was elevated in acute-stage patients, with higher levels associated with impaired white matter integrity in acute-stage and progressive gray and white matter atrophy from 3- to 6-12mo post-injury period. Collectively, our findings emphasized the potential clinical value of serum biomarkers, particularly NfL and VEGF, in diagnosing mTBI and monitoring disease progression.

Gas Chromatography-Mass Spectrometry Reveals Stage-Specific Metabolic Signatures of Ankylosing Spondylitis.

Ankylosing spondylitis (AS) is a type of chronic rheumatic immune disease, and the crucial point of AS treatment is identifying the correct stage of the disease. However, there is a lack of effective diagnostic methods for AS staging. The primary objective of this study was to perform an untargeted metabolomic approach in AS patients in an effort to reveal metabolic differences between patients in remission and acute stages. Serum samples from 40 controls and 57 AS patients were analyzed via gas chromatography-mass spectrometry (GC-MS). Twenty-four kinds of differential metabolites were identified between the healthy controls and AS patients, mainly involving valine/leucine/isoleucine biosynthesis and degradation, phenylalanine/tyrosine/tryptophan biosynthesis, glutathione metabolism, etc. Furthermore, the levels of fatty acids (linoleate, dodecanoate, hexadecanoate, and octadecanoate), amino acids (serine and pyroglutamate), 2-hydroxybutanoate, glucose, etc., were lower in patients in the acute stage than those in the remission stage, which may be associated with the aggravated inflammatory response and elevated oxidative stress in the acute stage. Multiple stage-specific metabolites were significantly correlated with inflammatory indicators (CRP and ESR). In addition, the combination of serum 2-hydroxybutanoate and hexadecanoate plays a significant role in the diagnosis of AS stages. These metabolomics-based findings provide new perspectives for AS staging, treatment, and pathogenesis studies.

Altered Neurovascular Coupling in Patients With Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-Like Episodes (MELAS): A Combined Resting-State fMRI and Arterial Spin Labeling Study.

Coupling between neuronal activity and blood perfusion is termed neurovascular coupling (NVC), and it provides a potentially new mechanistic perspective into understanding numerous brain diseases. Although abnormal brain activity and blood supply have been separately reported in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), whether anomalous NVC would be present is unclear. To investigate NVC changes and potential neural basis in MELAS by combining resting-state functional MRI (rs-fMRI) and arterial spin labeling (ASL). Prospective. Twenty-four patients with MELAS (age: 29.8 ± 7.3 years) in the acute stage and 24 healthy controls (HCs, age: 26.4 ± 8.1 years). Additionally, 12 patients in the chronic stage were followed up. 3.0 T, resting-state gradient-recalled echo-planar imaging and pseudo-continuous 3D ASL sequences. Amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), and functional connectivity strength (FCS) were calculated from rs-fMRI, and cerebral blood flow (CBF) was computed from ASL. Global NVC was assessed by correlation coefficients of CBF-ALFF, CBF-fALFF, CBF-ReHo, and CBF-FCS. Regional NVC was also evaluated by voxel-wise and lesion-wise ratios of CBF/ALFF, CBF/fALFF, CBF/ReHo, and CBF/FCS. Two-sample t-test, paired-sample t-test, Gaussian random fields correction. A P value <0.05 was considered statistically significant. Compared with HC, MELAS patients in acute stage showed significantly reduced global CBF-ALFF, CBF-fALFF, CBF-ReHo, and CBF-FCS coupling (P < 0.001). Altered CBF/ALFF, CBF/fALFF, CBF/ReHo, and CBF/FCS ratios were found mainly distributed in the middle cerebral artery territory in MELAS patients. In addition, significantly increased NVC ratios were found in the acute stroke-like lesions in acute stage (P < 0.001), with a recovery trend in chronic stage. This study showed dynamic alterations in NVC in MELAS patients from acute to chronic stage, which may provide a novel insight for understanding the pathogenesis of MELAS. 2 TECHNICAL EFFICACY: Stage 1.

Bioinformatics analysis and identification of hub genes of neutrophils in Kawasaki disease: a pivotal study.

Kawasaki disease (KD) is considered the main contributor to acquired heart diseases in developed countries. However, the precise pathogenesis of KD remains unclear. Neutrophils play roles in KD. This study aimed to select hub genes in neutrophils in acute KD. mRNA microarray of neutrophils from four acute KD patients and three healthy controls was performed to screen differentially expressed mRNAs (DE-mRNAs). DE-mRNAs were analyzed and predicted by Gene Ontology (GO), Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways, and protein-protein interaction networks. Real time-PCR was finally conducted to confirm the reliability and validity of the expression level of DE-mRNAs from blood samples of healthy controls and KD patients in both acute and convalescent stage. A total of 1950 DE-mRNAs including 1287 upregulated and 663 downregulated mRNAs were identified. GO and KEGG analyses revealed the DE-mRNAs were mainly enriched in the regulation of transcription from RNA polymerase II promoter, apoptotic process, intracellular signal transduction, protein phosphorylation, protein transport, metabolic pathways, carbon metabolism, lysosome, apoptosis, pyrimidine metabolism, alzheimer disease, prion disease, sphingolipid metabolism, huntington disease, glucagon signaling pathway, non-alcoholic fatty liver disease, pyruvate metabolism, sphingolipid signaling pathway, and peroxisome. Twenty hub DE-mRNAs were selected including GAPDH, GNB2L1, PTPRC, GART, HIST2H2AC, ACTG1, H2AFX, CREB1, ATP5A1, ENO1, RAC2, PKM, BCL2L1, ATP5B, MRPL13, SDHA, TLR4, RUVBL2, TXNRD1, and ITGAM. The real-time PCR results showed that BCL2L1 and ITGAM mRNA were upregulated in acute KD and were normalized in the convalescent stage. These findings may improve our understanding of neutrophils in KD. Key Points • Neutrophilic BCL2L1 and ITGAM mRNA were first reported to be correlated with the pathogenic mechanism of KD.

Difference in acute and chronic stage ischemic stroke metabolic markers with controls

BackgroundAcute Ischemic Stroke (AIS), a major cause of disability, was previously associated with multiple metabolomic changes, but many findings were contradictory. Case-control and longitudinal study designs could have played a role in that. To clarify metabolomic changes, we performed a simultaneous comparison of ischemic stroke metabolome in acute, chronic stages of stroke and controls. MethodsThrough the nuclear magnetic resonance (NMR) platform, we evaluated 271 serum metabolites from a cohort of 297 AIS patients in acute and chronic stages and 159 controls. We used Sparse Partial Least Squares-Discriminant analysis (sPLS-DA) to evaluate group disparity; multivariate regression to compare metabolome in acute, chronic stages of stroke and controls; and mixed regression to compare metabolome acute and chronic stages of stroke. We applied false discovery rate (FDR) to our calculations. ResultsThe sPLS-DA revealed separation of the metabolome in acute, chronic stages of stroke and controls. Regression analysis identified 38 altered metabolites. Ketones, branched-chain amino acids (BCAAs), energy, and inflammatory compounds were mostly elevated, while alanine and glutamine were decreased in the acute stage. These metabolites declined/increased in the chronic stage, often to the same levels as in controls. Levels of fatty acids, phosphatidylcholines, phosphoglycerides, and sphingomyelins did not change between acute and chronic stages, but were different comparing to controls. ConclusionOur pilot study identified metabolites associated with acute stage of ischemic stroke and those that are altered in stroke patients comparing to controls regardless of stroke acuity. Future investigation in a larger independent cohort is needed to validate these findings.

Computed Tomography Criteria for Differential Evaluation of True and False Lumens in Aortic Dissection

The aim of study Based on computed tomography data, to determine the most characteristic criteria for true lumen (TL) and false lumen (FL) in aortic dissection. To identify the relationship of the studied features with the stage of aortic dissection. Materials of the study Computed tomography (CT) data of 115 patients diagnosed with aortic dissection (AD) who were treated at the N.V. Sklifosovsky Research Institute for Emergency Medicine were analyzed. The average age of the patients was 54.5 years (median — 56 years), men predominated in the studied group. AD types according to the De Bakey classification were distributed as follows: Type I — in 47% of patients, Type II — in 16.5%, Type III — in 36.5%. Dissection in the acute stage occurred in 62% of the patient, in the subacute — in 16%, in the chronic — 22%. Results In the studied group, FL in all cases prevailed over the TL by size, regardless of the stage and type of AD. Analysis of lumen ratio showed that in 63.55% of patients, FL occupied 75% or more of the aortic cross-sectional area. Location of FL: at the level of the ascending aorta, along the right and anterior walls of the aorta — 94.5%; in the descending thoracic aorta, along the posterior and left walls — 84%; in the abdominal aorta, along the posterior and left walls — 70%. Calcifications of the non- dissected part of the aortic wall, as a sign of a true lumen, were found in 59.1%. There was no correlation between calcification and the AD stage. Partial thrombosis of one of the lumens was detected in 59% (in FL — 85%, in TL — 13%, thrombosis of both lumens — 2%). The beak signs occurred in 85% of patients with AD, however, it was significantly more often detected in patients with acute and subacute AD stages than in the chronic stage (p&lt;0.001). The cobweb sign was found in one third of patients with AD, however, it was statistically significantly more often determined in patients in acute and subacute stages (p&lt;0.05). Conclusion CT is reasonably considered a highly informative method of diagnosing AD. The signs of true and false lumen presented in the work, as well as their combination, make it possible to perform a quick and error-free marking of the aortic lumen with a high degree of probability. A number of the described CT signs correlate with the stage of AD.

Circulating Endothelial Cells: A New Possible Marker of Endothelial Damage in Kawasaki Disease, Multisystem Inflammatory Syndrome in Children and Acute SARS-CoV-2 Infection.

Background: Kawasaki Disease (KD) and Multisystem Inflammatory Syndrome in Children (MIS-C) are pediatric diseases characterized by systemic inflammation and vascular injury, potentially leading to coronary artery lesions (CALs). Data on vascular injury occurring during acute COVID-19 (AC19) in children are still lacking. The aim of our study was to investigate endothelial injury in KD-, MIS-C- and AC19-dosing circulating endothelial cells (CECs). Methods: We conducted a multicenter prospective study. CECs were enumerated by CellSearch technology through the immunomagnetic capture of CD146-positive cells from whole blood. Results: We enrolled 9 KD, 20 MIS-C and 10 AC19. During the acute stage, the AC19 and KD patients had higher CECs levels than the MIS-C patients. From the acute to subacute phase, a significant CEC increase was observed in the KD patients, while a mild decrease was detected in the MIS-C patients. Cellular clusters/syncytia were more common in the KD patients. No correlation between CECs and CALs were found in the MIS-C patients. The incidence of CALs in the KD group was too low to investigate this correlation. Conclusions: Our study suggests a possible role of CECs as biomarkers of systemic inflammation and endothelial dysfunction in KD and MIS-C and different mechanisms of vascular injury in these diseases. Further larger studies are needed.

Predictive Value of Serum Markers SFRP1 and CC16 in Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Background Chronic obstructive pulmonary disease (COPD) patients are particularly vulnerable to acute exacerbation, resulting in a huge socioeconomic burden. Objective In this study, we evaluated the value of serum secreted frizzled-related protein 1 (SFRP1) and Clara cell-secreted protein (CC16) in predicting the risk of acute exacerbations in patients with COPD. Methods The study included 123 COPD patients admitted to our hospital from May 2020 to June 2021, including 65 patients in stable stage (STCOPD group), 58 patients in acute exacerbation stage (AECOPD group), and 60 healthy volunteers (control group). Serum SFRP1 and CC16 levels were detected by enzyme-linked immunosorbent assay (ELISA). The receiver operating characteristics curve (ROC) analysis was performed to evaluate the sensitivity and specificity of serum SFRP1 and CC16 for predicting the risk of acute exacerbation in COPD patients. Results The age among groups is significantly different, but there is no difference in the gender and body mass index (BMI). The level of serum SFRP1 in the AECOPD group was significantly higher than that in the STCOPD group and the control group, and the level of serum CC16 was lower than that in the STCOPD group and the control group. Serum SFRP1 was negatively correlated with forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) (r = −0.473, P < 0.001). Serum CC16 was positively correlated with FEV1/FVC (r = 0.457, P < 0.001). The area under the curve (AUC), sensitivity, and specificity of SFRP1 for predicting the risk of exacerbation was 0.847 (95% CI: 0.775 to 0.920), 86.20%, and 80.00%. The AUC, sensitivity, and specificity of CC16 for predicting the risk of exacerbation were 0.795 (95% CI: 0.711 to 0.879), 74.10%, and 86.20%. Conclusions These findings suggest that SFRP1 and CC16 may be useful serum markers for predicting the risk of exacerbation in COPD patients.

Results of multiple ligament reconstruction after knee dislocation\u2014\u2014A prospective study with 95 patients and minimum 2-year follow up

BackgroundThere is still a lack of clinical data in arthroscopic treatment for treating multiple ligament injuries. This study aims to evaluate the clinical outcomes of patients with multiple ligament injuries undergoing treatment based on the classification stage and type of injury.MethodsA prospective, clinical trial on multiple ligament injuries was planned, which included 95 patients (58 men and 37 women; age: 42.8 ± 11.9 [range, 18–63] years) from October 2017 to June 2018. Injuries were classified into three stages (emergency stage < 24 h; acute stage: 24 h to 3 weeks, and chronic stage: > 3 weeks) and six types (KD I–VI) based on injuries time and structures, which indicated appropriate treatments. The clinical outcomes were evaluated at 2, 4, 6, 8, and 12 weeks and at 6, 9, 12 months and 24 months after surgery. The final choices in efficacy index included International Knee Documentation Committee (IKDC) score, Lysholm score, visual analog scale (VAS) score, and range of motion.ResultsDuring the follow-up, all patients exhibited statistically significant functional improvement in the injured limb compared with their preoperative situation. The mean postoperative scores of acute stage patients at 2-year follow-up were IKDC subjective score, 77.54 ± 11.53; Lysholm score, 85.96 ± 9.39; Tegner score, 4.13 ± 1.08; and VAS score, 1.21 ± 0.76. The mean postoperative scores of chronic stage patents at 2-year follow-up were IKDC subjective score, 74.61 ± 12.38; Lysholm score, 81.71 ± 10.80; Tegner score, 3.96 ± 1.14; and VAS score, 1.71 ± 0.60. The IKDC subjective score, Lysholm score, and Tegner score were significantly improved (P < 0.01) and the VAS score was significantly decreased (P < 0.01) at 2-year follow-up. Regarding the multiple ligament injuries classification, patients with more structural damage in stages V and VI showed less progress in functional recovery than those in stages I–IV.ConclusionsThis new classification with three stages and six types helps to identify the severity of injury and plan the management effectively. The outcomes were encouraging and the subjective functional results showed significant improvement at 2-year follow-up.Study designProspective clinical trial.Level of evidenceII

High-Resolution Magnetic Resonance Black Blood Thrombus Imaging and Serum D-Dimer in the Confirmation of Acute Cortical Vein Thrombosis.

Cerebral cortical vein thrombosis (CCVT) is often misdiagnosed because of its non-specific diagnostic symptoms. Here, we analyzed a cohort of patients with CCVT in hopes of improving understandings and treatments of the disease. A total of 23 patients with CCVT (confirmed with high-resolution imaging), who had been diagnosed between 2017 and 2019, were enrolled in this cohort study. Baseline demographics, clinical manifestations, laboratory data, radiological findings, treatment, and outcomes were collected and analyzed. Fourteen females and nine males were enrolled (mean age: 32.7 ± 11.9 years), presenting in the acute (within 7 days, n = 9), subacute (8–30 days, n = 7), and chronic (over 1 month, n = 7) stages. Headaches (65.2%) and seizures (39.1%) were the most common symptoms. Abnormally elevated plasma D-dimers were observed in the majority of acute stage patients (87.5%). The diagnostic accuracy of contrast-enhanced magnetic resonance venography (CE-MRV) and high-resolution magnetic resonance black-blood thrombus imaging (HR-MRBTI) in detecting CCVT were 57.1 and 100.0%, respectively. All patients had good functional outcomes after 6-month of standard anticoagulation (mRS 0–1) treatment. However, four CCVT patients that had cases involving multiple veins showed symptom relief after batroxobin therapy (p = 0.030). HR-MRBTI may be a fast and accurate tool for non-invasive CCVT diagnosis. HR-MRBTI combined with D-dimer can also precisely identify the pathological stage of CCVT. Batroxobin may safely accelerate cortical venous recanalization in combination with anticoagulation. Follow-up studies with larger sample sizes are suggested to evaluate the safety and efficacy of batroxobin for treating CCVT.

Treatment of hemorrhoids in a comorbid patient: selection of a preparation of plant origin

Real clinical practice is currently characterized by a significant increase in clinical situations, when it is already difficult to talk about the presence of only one disease in a patient, and in most clinical cases the patient has a combined or concomitant pathology.Hemorrhoidal disease has been known since ancient times and remains one of the most common human diseases. In the acute and initial stages of chronic hemorrhoids, conservative treatment is carried out. Its main goal is to relieve pain and inflammation, normalize blood circulation in the rectum. Given the high prevalence of hemorrhoids and the main risk factors for its development, which are simultaneously important in the development of other diseases and pathological conditions, a patient with hemorrhoids should be considered as a comorbid patient. Drug therapy for a comorbid patient always carries the risk of harm to the patient’s health by the drug itself, designed to resist the disease.Homeopathic medicines should be considered as a drug of choice for topical therapy in the management of uncomplicated forms of external haemorrhoids. In the presented review, the effects of the main components (Calendula officinalis, hamamelis virginiana, Aesculus hippocastanum, Mentholum, Zinci oxydum) of the ointment are considered and it is noted that the main medicinal properties of the combined preparation are anti-inflammatory, regenerating, disinfecting, drying effects. In conclusion, 2 clinical examples are given, indicating the effectiveness of the ointment in comorbid patients in acute and early stages of chronic hemorrhoids.

Caspases and therapeutic potential of caspase inhibitors in moderate-severe SARS-CoV-2 infection and long COVID.

BackgroundCOVID‐19 can present with lymphopenia and extraordinary complex multiorgan pathologies that can trigger long‐term sequela.AimsGiven that inflammasome products, like caspase‐1, play a role in the pathophysiology of a number of co‐morbid conditions, we investigated caspases across the spectrum of COVID‐19 disease.Materials & MethodsWe assessed transcriptional states of multiple caspases and using flow cytometry, the expression of active caspase‐1 in blood cells from COVID‐19 patients in acute and convalescent stages of disease. Non‐COVID‐19 subject presenting with various comorbid conditions served as controls.ResultsSingle‐cell RNA‐seq data of immune cells from COVID‐19 patients showed a distinct caspase expression pattern in T cells, neutrophils, dendritic cells, and eosinophils compared with controls. Caspase‐1 was upregulated in CD4+ T‐cells from hospitalized COVID‐19 patients compared with unexposed controls. Post‐COVID‐19 patients with lingering symptoms (long‐haulers) also showed upregulated caspase‐1activity in CD4+ T‐cells that ex vivo was attenuated with a select pan‐caspase inhibitor. We observed elevated caspase‐3/7levels in red blood cells from COVID‐19 patients compared with controls that was reduced following caspase inhibition.DiscussionOur preliminary results suggest an exuberant caspase response in COVID‐19 that may facilitate immune‐related pathological processes leading to severe outcomes. Further clinical correlations of caspase expression in different stages of COVID‐19 will be needed.ConclusionPan‐caspase inhibition could emerge as a therapeutic strategy to ameliorate or prevent severe COVID‐19.

Association of СОМТ, DRD2/ANKK1, MTHFR, MIR 137, DNMT3B polymorphisms with the clinical features of schizophrenia patients in acute stage and remission

Updated view of genetic features of schizophrenia based on rare SNPs/CNVs with a huge influence on a disease and common SNPs with a small effect of each allele is presented. Altogether these genetic factors are acting to create neuropathophysiological disturbances observed in schizophrenia. Association of five polymorphisms MIR137 rs1625579, DRD2/ANKK1 rs1800497, MTHFR rs1801133, DNMT3B rs2424913, СОМТ rs4680 with the risk of schizophrenia in the Belarusian population, the level of symptoms of schizophrenia patients assessed by PANSS in the acute stage and remission, cognitive impairments, and treatment trajectory of schizophrenia patients during antipsychotic treatment were analyzed. The A/A-genotype of СОМТ rs4680 (р = 0.008) and the С/С-genotype of MTHFR rs1801133 (р = 0.02) are associated with the risk of schizophrenia among Belarusians. The T-allele of MTHFR rs1801133 is a risk factor of positive symptoms (р = 0.02). Combining the C/C-genotype (DNMT3B rs2424913) and the G-allele (COMT rs4680) is associated with a significant difference in negative symptoms level between men and women. The polymorphism of СОМТ rs4680 (р &lt; 0.05) and the combination of СОМТ rs4680 + DRD2/ANKK1 rs1800497 (р = 0.005) as well as MTHFR rs1801133 + DNMT3B rs2424913 (р = 0.006) are related to the cognitive parameters measured by the WCST and Stroop test respectively. Schizophrenia patients who are the G-allele carriers of MIR137 rs1625579 demonstrated a more favorable negative symptom trajectory in comparison to Т/Тhomozygotes (F = 2.2, p = 0.03). The trajectory of negative symptoms (F = 2.2, p = 0.03) and general psychopathological symptoms (F = 4.3, p = 0.0001) is different between men and women under antipsychotic treatment. These differences are associated with a minor amount of alleles of MIR137 rs1625579, DRD2/ANKK1 rs1800497, MTHFR rs1801133 polymorphic sites.

Postural Assessment Scale for Stroke Patients in Acute, Subacute and Chronic Stage: A Construct Validity Study.

(1) Background: Observational scales are the most common methodology used to assess postural control and balance in people with stroke. The aim of this paper was to analyse the construct validity of the Postural Assessment Scale for Stroke Patients (PASS) scale in post-stroke patients in the acute, subacute, and chronic stroke phases. (2) Methods: Sixty-one post-stroke participants were enrolled. To analyze the construct validity of the PASS, the following scales were used: the Functional Ambulatory Category (FAC), the Wisconsin Gait Scale (WGS), the Barthel Index (BI) and the Functional Independence Measure (FIM). (3) Results: The construct validity of the PASS scale in patients with stroke at acute phase was moderate with the FAC (r = −0.791), WGS (r = −0.646) and FIM (r = −0.678) and excellent with the BI (r = 0.801). At subacute stage, the construct validity of the PASS scale was excellent with the FAC (r = 0.897), WGS (r = −0.847), FIM (r = −0.810) and BI (r = −0.888). At 6 and 12 months, the construct validity of the PASS with the FAC, WGS, FIM and BI was also excellent. (4) Conclusions: The PASS scale is a valid instrument to assess balance in post-stroke individuals especially, in the subacute and chronic phases (at 6 and 12 months).

Post-stroke object affordances: An EEG investigation

Rehabilitating upper limb function after stroke is a key therapeutic goal. In healthy brains, objects, especially tools, are said to cause automatic motoric ‘affordances’; affecting our preparation to handle objects. For example, the N2 event-related potential has been shown to correlate with the functional properties of objects in healthy adults during passive viewing. We posited that such an affordance effect might also be observed in chronic-stage stroke survivors. With either dominant or non-dominant hand forward, we presented three kinds of stimuli in stereoscopic depth; grasp objects affording a power-grip, pinch objects affording a thumb and forefinger precision-grip and an empty desk, affording no action. EEG data from 10 stroke survivors and 15 neurologically healthy subjects were analysed for the N1 and N2 ERP components. Both components revealed differences between the two object stimuli categories and the empty desk for both groups, suggesting the presence of affordance-related motor priming from around 100 to 370 ms after stimulus onset. Hence, we speculate that stroke survivors with loss of upper limb function may benefit from object presentation regimes designed to maximise motor priming when attempting movements with manipulable objects. However, further investigation would be necessary with acute stage patients, especially those diagnosed with apraxia.

Correlative factors analysis and predictive model construction of intestinal flora imbalance during acute exacerbation of chronic obstructive pulmonary disease

Objective: To explore correlative factors and construct predictive model of intestinal flora imbalance in patients with acute exacerbation of Chronic Obstructive Pulmonary Disease (COPD). Methods: The patients in acute exacerbation stage of COPD (AECOPD) hospitalized in Yixing People's Hospital from January 1 to December 31, 2019 were included. According to the clinical symptoms and results of fecal examination, the subjects were divided into case group (n=45) and control group (n=83). Multivariate logistic regression was used to analyze the correlative factors of intestinal flora imbalance in AECOPD patients. The prediction model of intestinal flora imbalance in patients with AECOPD was constructed according to the results of factor logistic regression analysis, and the effectiveness of the prediction model was evaluated by receiver operating characteristic (ROC) curve analysis. Results: The ages of subjects in case group and control group were (76±9) and (74±8) years old, respectively, among which males accounted for 80.0% (36/45) and 69.9% (58/83), respectively. The multivariate logistic regression model analysis showed that serum albumin concentration, frequency of acute exacerbation ≥2 times/year, complicated with chronic cor pulmonale and diabetes mellitus were correlative factors of intestinal flora imbalance in patients with AECOPD. The OR (95%CI) were 0.98 (0.80-0.97), 3.70 (1.79-11.72), 2.62 (1.46-10.80) and 3.85 (1.17-8.58), respectively. The prediction model of intestinal flora imbalance was logit P=3.858-0.13×serum albumin consentration+1.52×acute exacerbation ≥2 times/year+1.379×chronic cor pulmonale+1.155×diabetes mellitus. The area under the ROC curve of this model was 0.847 and the sensitivity and specificity of the prediction model were 88.9% and 71.1%, respectively. Conclusions: Serum albumin, frequency of acute exacerbation ≥2 times/year, complicated with chronic cor pulmonale and diabetes mellitus are correlative factors of intestinal flora imbalance in patients with AECOPD. The predictive model shows high clinical value in predicting intestinal flora imbalance in patients with AECOPD.

Serum level of IL-1β in patients with inflammatory demyelinating disease: Marked upregulation in the early acute phase of MOG antibody associated disease (MOGAD)

BackgroundTo evaluate the serum cytokine profiles in patients with myelin oligodendrocyte glycoproteins antibody associated disease (MOGAD), compared to those in neuromyelitis optica spectrum disorder with aquaporin-4 immunoglobulin G (APQ4-IgG+ NMOSD), multiple sclerosis (MS), and other inflammatory demyelinating diseases (IDDs). MethodsThe level of interleukin (IL)-1β, IL-5, IL-6, IL-10, IL-12p70, IL-17A, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ in sera from 21 patients with MOGAD, 32 APQ4-IgG+ NMOSD, 24 MS, and 16 other IDDs were assessed. ResultsIn MOGAD patients, the levels of IL-1β and IL-12p70 were elevated compared to APQ4-IgG+ NMOSD. The level of IL-10 and the ratio of T helper (Th)-1/Th2-related cytokines were elevated in MOGAD patients compared to MS or other IDDs. In an intragroup analysis, the IL-1β was increased in acute stage of MOGAD, APQ4-IgG+ NMOSD, and also MS compared to their chronic stage counterpart. It was inversely correlated with time from acute attack to sampling in MOGAD (p < 0.001) and AQP4-IgG+ NMOSD (p = 0.001), but not in MS. Moreover, the IL-1β was most markedly upregulated in MOGAD sera sampled within 1 week from acute attack compared to those sampled after (p = 0.002). ConclusionsThe serum IL-1β can be elevated in the acute stage of patients with diverse IDDs including, MOGAD, APQ4-IgG+ NMOSD, and MS. This upregulation of serum IL-1β can be most markedly observed in the early acute stage of MOGAD patients. Further studies seem to be needed to determine the proper mechanism for the upregulation of serum IL-1β and also the role of IL-1β inhibition especially at the early acute stage of MOGAD.

Retinal Microcirculation Defects on OCTA Correlate with Active Inflammation and Vision in Vogt–Koyanagi–Harada Disease

ABSTRACT Purpose: To analyze quantitative OCT-angiography (OCTA) measurements of Vogt-Koyanagi-Harada (VKH) disease at different disease stages. Methods: OCTA scans of 110 VKH patients in acute uveitic, convalescent and chronic recurrent stage were reviewed; posterior uveitis recurrent cases were excluded. Superficial and deep capillary plexus (SCP and DCP) vascular densities (VD) and subfoveal choroidal thickness (SFCT) were compared. Results: DCP VD was significantly lower and SFCT higher in VKH than normal controls (NC) in all 3 stages (all p < .001). Anterior uveitis recurrent patients had lower SCP and DCP VDs and thicker SFCT than convalescent patients (p = .001, p < .001, and p = .003, respectively). DCP VD was significantly correlated with visual acuity (p < .05). Patients with history of anterior recurrence had lower retinal VDs in the convalescent stage than those without (p < .001). Conclusion: Retinal microcirculation is impaired in VKH. DCP VD might be a sensitive indicator of inflammatory status and appeared to be well associated with visual outcome.