Changes In Clinical Status Research Articles

Treatment Tactics in Remission Stage of Episodic Schizophrenia Taking into Account Immunological Parameters

Background: the study of clinical remission in schizophrenia has a significant place at the current stage of development of psychiatric science. Prevention therapy and personalized prophylactic therapy is important to improve the quality of remission, stabilization of the endogenous process and prevention of exacerbation. The aim was to develop apathogenetically grounded method of treatment of episodic schizophrenia at the remission stage using complex assessment of clinical, psychometric and immunological parameters of patients, which allows to control the quality and stability of remission, as well as prediction of exacerbation of the endogenous process. Patients and methods: 91 patients (24 men and 67 women) aged from 18 to 70 years were examined. They were in remission after suffering attacks of an endogenous disease with episodic course (the duration of remissions ranged from 6 months to 12 years). Clinical-psychopathological, psychometric, immunological, clinical and followup, and statistical methods were used. Results: determination of inflammatory and autoimmune markers of blood plasma in the dynamics of the disease and their comparison with the severity of psychopathological symptomatology of patients with schizophrenia, made it possible to form 2 groups of patients with differently directed correlations between the change in clinical state (according to the PANSS scale) and the level of activation of the immune system, assessed in the aggregate immune markers determined. For patients of group 1 (n = 58; 63.74%) the decrease of the intensity of psychopathological symptoms in remission is associated with a decrease in the level of immune system activation («positive» correlations). For the patients of group 2 (n = 33; 36.26%) the level of immune system activation in remission does not decrease and remains at the level of the acute stage of the disease (“negative” correlations). It is shown that the increase in the level of immune system activation in patients of group 1 is a prognostic immunological criterion of possible exacerbation of psychopathological symptoms in remission. Based on the determination of immunological blood parameters in remission, personalized treatment tactics have been developed for these patients, associated with the transition from maintenance doses of drugs to therapeutic ones or additional use of drugs of another group. In most cases, this tactic contributed to relatively favorable dynamics of the existing clinical remission without significant changes in the condition. For patients of group 2, the personalized therapy tactics involves continuation of longterm active therapy. Conclusions: complex assessment of clinical, psychometric and immunological parameters of patients with episodic schizophrenia, which allows to control the quality and stability of remission, can be used to control the quality and stability of remission, as well as to detect preclinical signs of exacerbation of the endogenous process.

Inflammatory Neuropathy Consortium base (INCbase): a protocol of a global prospective observational cohort study for the development of a prediction model for treatment response in chronic inflammatory demyelinating polyneuropathy

BackgroundINCbase is an international, multicenter prospective observational study using a customizable web-based modular registry to study the clinical, biological and electrophysiological variation and boundaries of chronic inflammatory demyelinating polyneuropathy (CIDP). The primary objective of INCbase is to develop and validate a clinical prediction model for treatment response.MethodsAll patients meeting clinical criteria for CIDP can be included in INCbase. Collected data include demographics, clinical history, diagnostics and various domains of clinical outcomes. Data is collected at a minimum of every 6 months for two years, and more frequently at the discretion of the investigational site to allow for assessment of unexpected changes in treatment response or clinical status. Participants can be enrolled in various sub-studies designed to capture data relevant to specific groups of interest. Data is entered directly into the web-based data entry system by local investigators and/or participants. Collection and local storage of biomaterial is optional. To develop a clinical prediction model for treatment response, newly diagnosed patients with active disease warranting start of first-line treatment will be included. The study population will be split into a development and validation cohort. Univariate and multivariate logistic regression analysis will be used to identify and combine predictors at start of treatment for treatment response at six months. Model performance will be assessed through discrimination and calibration in an external validation cohort. The externally validated prediction model will be made available to researchers and clinicians on the INCbase website.DiscussionWith this study, we aim to create a clinically relevant and implementable prediction model for treatment response to first line treatments in CIDP. INCbase enrollment started in April 2021, with 29 centers across 8 countries and 303 patients participating to date. This collaborative effort between academia, patient advocacy organizations and pharmaceutical industry will deepen our understanding of how to diagnose and treat CIDP.

Outcomes of Catheter Directed Thrombolysis for Early and Late Re-occlusions in Acute Lower Limb Ischemia.

Acute lower limb ischemia (ALI) is a sudden decrease in arterial limb perfusion due to an arterial blockage, threatening limb and life. Catheter-directed thrombolysis (CDT) is a minimally invasive procedure to remove such obstructions. However, approximately one-third of patients endure a re-occlusion after successful CDT. This study aimed to investigate the short- and long-term outcomes of CDT for early (<1 year) and late (>1 year) re-occlusions. This retrospective multicenter study reviewed patients from 2 medical centers with an acute arterial re-occlusion of the lower limb after successful CDT between December 1996 and April 2021. The primary endpoints were angiographic success, defined as thrombus dissolution over 95% with outflow to at least 1 crural artery, and clinical success, defined as a score of ≥1 on the Rutherford scale for assessing changes in clinical status. Secondary endpoints included bleeding complications, patency, amputation, and mortality. Kaplan-Meier analyses were used to estimate patency, survival, and freedom from amputation. Seventy-seven cases were included, with 52 early re-occlusions (<1 year) and 25 late re-occlusions (>1 year). The median time to re-occlusion since the last CDT treatment was 4 months in the early re-occlusion group and 24 months in the late re-occlusion group. Angiographic success was achieved in 73% of early and 64% of late re-occlusions. Clinical success rates were 80.8% for the early and 80.0% of the late re-occlusion cases. Major bleeding occurred in 2% of the early and 8% of the late re-occlusion group. Patients were followed up until symptoms or signs of limb ischemia were resolved, with a median follow-up time of 15 months for the early and 22 months for the late re-occlusion group. During follow-up, secondary re-occlusions were observed in 59.6% of the early and 44% in the late group. Cumulative amputation rates at 1, 5, and 8 years were 36%, 36%, and 52% for early and 18%, 30%, and 30% for the late re-occlusions, respectively. In our experience, CDT is an effective short-term revascularization strategy for the majority of patients with both early and late re-occlusions. Long-term results are limited by secondary re-occlusions and limb loss. Catheter-directed thrombolysis (CDT) is a well-established treatment for acute lower limb ischemia (ALI). Re-occlusions after successful treatment are, however, observed in almost a third of the patients. Yet, the outcomes of CDT for re-occlusions for patients who were previously treated with CDT are not well known. This study showed that CDT is effective in achieving revascularization in cases of early and late re-occlusion after treatment for ALI, but the risk for further re-occlusions is high. Future studies should focus on maintaining patency after successful CDT for ALI.

Technical Approaches for Coil Embolization of Unruptured Small Anterior Choroidal Artery Aneurysms: A Focus on Anatomical Flow Preservation of the Anterior Choroidal Artery.

The anterior choroidal artery (AChA) supplies the corticospinal tract related to the motor function of the upper and lower limbs. Aneurysms arising at the AChA are not common and exhibit various patterns of involvement of the AChA. Hence, managing an AChA aneurysm poses a high risk of neurological deficits. We report technical issues related to the outcome of coil embolization for unruptured AChA aneurysms. We obtained Institutional Review Board approval for this study. In the past 2 years, 18 consecutive patients (6 males and 12 females, aged 32-68) with unruptured AChA aneurysms were treated using embolization. We present technical details, pre- and post-procedural patient statuses, angiographic outcomes, and recurrence during a mean follow-up period of 12 months (range 3-25). The patients with AChA (n=18) underwent stent-assisted coiling (n=14), coiling (n=2), or stenting only (n=2). The technical strategy for aneurysm embolization included a low-lying approach into the aneurysm, stent-strut abutting (protecting) coil framing to block inflow and avoid compromising AChA flow, and direct intra-aneurysmal angiography via a microcatheter. Angiographic results showed complete occlusion (n=11), neck remnant (n=5), and sac remnant (n=2). During the follow-up, there were 2 recurrences, and 1 of them required a re-procedure. All patients showed no change in clinical status (modified Rankin scale score=0) and did not experience any ischemic or hemorrhagic events during the follow-up period. AChA aneurysms can be managed through embolization using various techniques. Such technical concepts may enhance the safety and improve the outcomes of AChA aneurysm embolization.

Changes in the HIV Epidemic in Lower Silesia, Poland, Between 2010 and 2020: The Characteristics of the Key Populations.

The HIV (Human Immunodeficiency Virus) epidemic remains a significant public health issue, requiring ongoing access to preventive methods. This study aimed to analyze the evolution of the HIV epidemic in Lower Silesia from 2010 to 2020, focusing on the key populations. A retrospective analysis of the medical records from newly diagnosed HIV patients at a major HIV clinic in Wroclaw was conducted, examining demographic data, infection routes, and laboratory results. An 84% increase in newly diagnosed HIV cases was observed over the decade, with the most common route of infection being sex between men (70% among those with a known infection route). These patients were generally in better clinical condition compared to their heterosexual counterparts, as indicated by a higher median CD4+ T cell count (465/μL vs. 250/μL). The changes in clinical status and infection routes were statistically significant. The HIV epidemic in Lower Silesia has shifted, with a notable rise in new infections among men who have sex with men. Heterosexual patients were often diagnosed at more advanced stages. Prevention strategies should adapt to these changing trends, with education and testing accessibility remaining priorities nationwide.

Predictors of long-term clinical outcomes after TIPS: An ALTA group study.

While transjugular intrahepatic portosystemic shunt (TIPS) is traditionally considered a bridge to liver transplant (LT), some patients achieve long-term transplant-free survival (TFS) with TIPS alone. Prognosis and need for LT should not only be assessed at time of procedure, but also re-evaluated in patients with favorable early outcomes. Adult TIPS recipients in the multicenter Advancing Liver Therapeutic Approaches retrospective cohort study were included (N=1,127 patients; 2,040 person-years follow-up). Adjusted competing risk regressions were used to assess factors associated with long-term post-TIPS clinical outcomes at time of procedure and at 6 months post-TIPS. MELD-Na at TIPS was significantly associated with post-TIPS mortality (sHR of death 1.1 [p=0.42], 1.3 [p=0.04], and 1.7 [p<0.01] for MELD-Na 15-19, 20-24, and ≥25 relative to MELD-Na <15, respectively). MELD 3.0 was also associated with post-TIPS outcomes. Among the 694 (62%) patients who achieved early (6mo) post-TIPS TFS, rates of long-term TFS were 88% at 1-year and 57% at 3-years post-TIPS. Additionally, a within-individual increase in MELD-Na score of >3 points from TIPS to 6 months post-TIPS was significantly associated with long-term mortality, regardless of initial MELD-Na score (sHR of death 1.8, p<0.01). For patients with long-term post-TIPS TFS, rates of complications of the TIPS or portal hypertension were low. Among patients with early post-TIPS TFS, prognosis and need for LT should be reassessed, informed by post-procedure changes in MELD-Na and clinical status. For selected patients, "destination TIPS" without LT may offer long-term survival with freedom from portal hypertensive complications.

Associations of ambient air pollution with incidence and dynamic progression of atrial fibrillation

The influence of air pollution on dynamic changes in clinical state from healthy to atrial fibrillation (AF), further AF-related complications and ultimately, death are unclear. We aimed to investigate the relationships between air pollution and the occurrence and progression trajectories of AF. We retrieved 442,150 participants free of heart failure (HF), myocardial infarction (MI), stroke and dementia at baseline from UK Biobank. Exposures to air pollution for each transition stage were estimated at the geocoded residential address of each participant using the bilinear interpolation approach. The outcomes were incident AF, complications, and death. Multi-stage models were used to evaluate the associations between air pollution and dynamic progression of AF. Over a 12.6-year median follow-up, a total of 21,670 incident AF patients were identified, of whom, 4103 developed complications and 1331 died. PM2.5, PM10, NOx and NO2 were differentially positively associated, while O3 was negatively associated with risks of progression trajectories of AF. PM2.5 exposure was significantly associated with an increased risk of progression. The associations of PM2.5, PM10, NOx, and NO2 on incident AF were generally more pronounced compared to other transitions. The cumulative transition probabilities were generally higher in individuals with higher exposure levels of PM2.5, PM10, NOx, and NO2 and lower exposure to O3. Air pollution could potentially have a role in increasing the risk of both the occurrence and progression of AF, emphasizing the significance of air pollution interventions in both the primary prevention of AF and the management of AF-related outcomes.

Improving the clinical meaning of surrogate endpoints: An empirical assessment of clinical progression in phase III oncology trials.

Disease progression in clinical trials is commonly defined by radiologic measures. However, clinical progression may be more meaningful to patients, may occur even when radiologic criteria for progression are not met, and often requires a change in therapy in clinical practice. The objective of this study was to determine the utilization of clinical progression criteriawithin progression-based trial endpoints among phase III trials testing systemic therapies for metastatic solid tumors. The primary manuscripts and protocols of phase III trials were reviewed for whether clinical events, such as refractory pain, tumor bleeding, or neurologic compromise, could constitute a progression event. Univariable logistic regression computed odds ratios (OR) and 95% CI for associations between trial-level covariates and clinical progression. A total of 216 trials enrolling 148,190 patients were included, with publication dates from 2006 through 2020. A major change in clinical status was included in the progression criteria of 13% of trials (n = 27), most commonly as a secondary endpoint (n = 22). Only 59% of trials (n = 16) reported distinct clinical progression outcomes that constituted the composite surrogate endpoint. Compared with other disease sites, genitourinary trials were more likely to include clinical progression definitions (16/33 [48%] vs. 11/183 [6%]; OR, 14.72; 95% CI, 5.99 to 37.84; p < .0001). While major tumor-related clinical events were seldom considered as disease progression events, increased attention to clinical progression may improve the meaningfulness and clinical applicability of surrogate endpoints for patients with metastatic solid tumors.

Abstract Tu041: Gut microbiome Bifidobacterium is associated with improvement in severity of heart failure with reduced ejection fraction

Background: Heart failure (HF) has been associated with dysregulated gut microbiome. However, less is understood about how gut microbiome alterations relate to changes in HF severity. We sought to understand how gut microbial shifts and associated host signatures related to changes in clinical status of patients with HF with reduced ejection fraction (HFrEF). Methods: Twenty-six adults with HFrEF were recruited and completed 2 study visits approximately 6 months apart. At each visit they provided stool sample for microbiome profiling (metagenomic sequencing), and fasting blood samples for untargeted metabolomics (liquid chromatography–mass spectrometry) and cytokine assay (Luminex antibody-conjugated bead capture). Subjects also completed dietary surveys. Clinical improvement was measured as between-visit change in the New York Heart Association (NYHA) class. Results: Between-visit NYHA class improved in 6 individuals; 20 patients remained stable or worsened. After accounting for demographics, body mass index, and diet, genus Bifidobacterium was significantly enriched in the improved group and increased over time (Figure 1). Bifidobacterium was directly associated with circulating malonic acid, which is implicated in cardio-protection and cardiomyocyte regeneration, and with indole-3-propionate (IPA), anti-inflammatory gut microbial metabolite of dietary tryptophan (Figure 2). There was also a positive correlation between Bifidobacterium and IL10, a major anti-inflammatory cytokine that plays a role in cardiac remodeling. Conclusion: Bifidobacterium was independently associated with longitudinal improvement in functional status in patients with HFrEF. Additionally, Bifidobacterium correlated with circulating IPA, malonic acid, and IL10. Our findings support (1) gut Bifidobacterium as a potential biomarker of clinical improvement in HFrEF and a possible new therapeutic target, and (2) potential downstream mediators through which Bifidobacterium may regulate HF pathophysiology.

Muscle ultrasound in myopathies.

This review highlights recent developments in the field of muscle ultrasound (MUS) for the diagnosis and follow up of muscle disorders. The diagnostic screening capacity of quantitative grayscale analysis is still sufficient to assess children suspected of a neuromuscular disorder. A combination of visual and quantitative assessment is advised for optimal interpretation. MUS was more sensitive but less specific than MRI for detecting pathology in limb girdle dystrophies and inflammatory myopathies. New techniques such as shearwave elastography and artificial intelligence algorithms for automated image segmentation show promise but need further development for use in everyday practice.Muscle ultrasound has high correlations with clinical measures of function in skeletal and respiratory muscles and the orofacial region, in most of the myopathies and dystrophies studied. Over time, imaging changes precede changes in clinical status, making them attractive for biomarker use in trials. In Duchenne muscular dystrophy MUS was also responsive to the effects of steroid treatment. Muscle ultrasound is a sensitive technique to diagnose and follow up of skeletal, facial and respiratory muscles in neuromuscular disorders. Its role is both complementary to and partially overlapping with that of MRI.

Factors Influencing Documentations of Nursing Procedures among Nurses at St. Daniel Comboni Hospital, Kyamuhunga

Documentation provides an accurate reflection of nursing assessments, changes in clinical state, care provided, and pertinent patient information to support the multidisciplinary team to deliver individualized care. The main purpose of this research study was to assess the factors influencing the documentation of nursing procedures among nurses at St. Daniel Comboni Hospital, Kyamuhunga. A quantitative descriptive cross-sectional study was used on over 50 participants who were nurses working at St. Daniel Comboni Hospital and they were selected by simple random sampling technique. The participants were interviewed using a semi-administered questionnaire and the data generated analysed using SPSS version 22.0. Results showed that out of 50 participants, 100.0 % had never heard about nursing documentation, 58.0 % were below 25 years with 76.0 % were enrolled nurses and 46.0% had less than 3 years of experience. 52.0 % reported good working conditions, 76.0 % were satisfied with the facilitation, 92.0 % said documentation of nursing procedures is good for better health outcomes of the patients, and 90.0 % said after their successors they continue with nursing documentation. 74.0 % said that they had all the supplies necessary to carry out nursing documentation. 80.0 % didn’t have any other duties apart from nursing duties. Even though all 100.0 % of the participants had ever heard about nursing documentation yet, documentation of nursing procedures was negatively influenced by stressful working conditions (46.0%), lack of nursing documentation charts in the wards/units (61.4%), having additional duty mainly supervisory duty (50.0%). The majority of the participants reported good working conditions (52.0%) and were satisfied with the facilitation they are receiving from the facility 76.0%. Keywords: Factors Influencing, Documentations, Nursing Procedures, Nurses

Peri-mortem arrhythmias in the non-cardiac intensive care unit.

Cardiovascular failure is recognized as a common final pathway at the end of life but there is a paucity of data describing terminal arrhythmias. We aimed to describe arrhythmias recorded peri-mortem in critically ill patients. We enrolled intensive care unit patients admitted to two tertiary Canadian medico-surgical centres. Participants wore a continuous electrocardiogram (ECG) monitor for 14 days, until discharge, removal or death. We recorded all significant occurrences of arrhythmias in the final hour of life. Among 39 patients wearing an ECG monitor at the time of death, 22 (56%) developed at least 1 terminal arrhythmia as adjudicated by an arrhythmia physician: 23% (n = 9) had ventricular fibrillation/polymorphic ventricular tachycardia, 18% (n = 7) had sinoatrial pauses, 15% (n = 6) had atrial fibrillation and 13% (n = 5) had high-degree atrioventricular block. Five participants (13%) developed multiple arrythmias. Arrhythmias are common in dying critically ill patients. There is a roughly even distribution between ventricular arrhythmias, atrial fibrillation, sinus node dysfunction and atrioventricular block. The results of this study may be most useful for critically ill patients who are organ donation candidates. The appearance of arrhythmias may serve as a marker of change in clinical status for organ donation teams to plan mobilization efforts. In participants who are sedated or intubated, arrhythmias could be a surrogate marker for respiratory or neurologic changes.

A Phase 3, Randomized, Controlled Trial Evaluating the Efficacy and Safety of Ropeginterferon Alfa-2b in Patients with Moderate COVID-19.

Ropeginterferon alfa-2b is a novel mono-pegylated proline-interferon. This clinical study aimed to evaluate its antiviral efficacy of ropeginterferon alfa-2b against SARS-CoV-2 infection. This is a multicenter, randomized, open-label study. Adult patients with confirmed SARS-CoV-2 infection with initial cycle threshold (Ct) value<30 and symptom onset within 4days were enrolled. Eligible patients were randomized in a 2:1 ratio to receive a single 250-µg dose of ropeginterferon alfa-2b subcutaneously plus standard of care (SOC) or to receive SOC alone. The primary endpoint was the proportion of patients with a negative RT-PCR result for SARS-CoV-2 or discharged from the hospital before Day 8. Change in clinical status based on the World Health Organization (WHO) clinical progression scale and pulmonary infiltrations through chest radiograph were also evaluated. A total of 132 patients were enrolled and treated with study medication. Higher percentages of patients who achieved Ct≥30 or were discharged from the hospital were observed on Day 8 and every other time point of assessment, i.e., Days 5, 11, 15, and 22, in the ropeginterferon alfa-2b group compared to the SOC alone group. However, the difference was statistically significant on Day 11 but not on Day 8. The primary endpoint was not met. The ropeginterferon alfa-2b group showed a higher improvement rate in lung infiltration on Day 5 (27.6% vs. 0.0%, p=0.0087) and a higher improvement rate in WHO clinical progression scores on Day 8 (69.4% vs. 35.3%, p=0.03) than those in the SOC group. No ropeginterferon alfa-2b-related serious adverse event was observed. Our data show that ropeginterferon alfa-2b with SOC shortened the duration of SARS-CoV-2 shedding compared with SOC alone. In addition, ropeginterferon alfa-2b as an additional therapy could be beneficial by improving lung infiltration.

Gait Assessment in Chronic Inflammatory Demyelinating Polyradiculoneuropathy

Background and Aims. Gait impairment is a common manifestation of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). However, clinicians lack an effective monitoring tool, as no gait test has been validated for CIDP. The aim of this study was to determine the usefulness of three tests in monitoring the clinical course of patients with CIDP: Timed Up and Go (TUG), 10-Meter Walk Test (10MWT), and 30-Second Chair Stand (30SCS). Methods. This is a prospective, single-center observational study. We included newly diagnosed CIDP patients starting treatment or relapsed CIDP patients requiring new treatment. We monitored the clinical course using CIDP-validated clinical scales and correlated changes in clinical status with the results of the gait tests. A ROC curve was developed, and we chose the cut-off point on each scale with the best specificity and sensitivity to detect change in clinical status. Results. A total of 20 patients have been recruited. The 3 tests show a statistical correlation with objective clinical improvement. In patients who have showed clinical improvement during the follow-up examination, a mean reduction of 4.8 seconds in TUG and 2.6 in 10MWT and a gain of 3 repetitions in 30SCS have been observed. The optimal cut-off points for each test were TUG≤1 seconds, 10MWT≤1 seconds, and 30SCS≥1 repetition. The TUG test has the highest sensitivity (82.6%), and the 30SCS test has the highest specificity (100%) for detecting clinical improvement. Conclusions. The study found that the TUG and 30SCS tests could become effective tools for monitoring treatment response in CIDP patients.

Abdominal trauma: Clinical monitoring, an overlooked yet essential ally

Abdominal traumas are a frequent emergency and are associated with significant morbidity and mortality in spite of improved recongnition, diagnosis and management. Trauma is the second largest cause of disease accounting for 16% of global burden. Approach to trauma should be systemic and prioritized. The hemodynamically unstable patient should undergo expedient sonography to rule out abdominal haemorrhage. The use of computer tomography (CT) in this difficult patient group is also currently evaluated; however it takes specific amendments to the protocol and institution. In the hemodynamically stable patient however, computed tomography is the modality of choice to evaluate the injured abdomen. Non operative treatment can be successful in up to 80% of selected cases. This article objective the interest of close monitoring in the management of abdominal trauma, this monitoring reduces the rate of surgical intervention in clinically stable patients and also allows to propose a delayed surgery if the patient’s clinical or radiological status changes during monitoring.

ПРИМЕНЕНИЕ СИНТЕТИЧЕСКОГО ИМПЛАНТАТА НА ОСНОВЕ ГИДРОКСИАПАТИТА И ВОЛЛАСТОНИТА ДЛЯ СТИМУЛЯЦИИ ПРОЦЕССОВ РЕГЕНЕРАЦИИ КОСТНОЙ ТКАНИ

The aim of the study is to evaluate the efficiency of using bone substitute material grounded on hydro-xyapatite and wollastonite based on changing clinical status indicators, radiographic examination and hematological parameters. A preclinical study was conducted at the Faculty of Veterinary Medicine, Institute of Veterinary Medicine and Biomedical Sciences, Omsk State Agrarian University named after P.A. Stolypin. The object of the study was laboratory rabbits (n = 10) of the white New Zealand breed, HYCOLE genetics, aged (13 ± 1.2) months, weighing (4.78 ± 0.37) kg with a formed model of cortical bone defect of the femur in the distal metaphysis area. To evaluate the efficiency, the animals were divi-ded into 2 groups. Animals for the study were selected using the analog method. In animals from group I, the defect cavity was closed with SiHA granules. Group II remained intact without replenishment of the cortical defect. The dynamics of reparative processes were monitored using clinical, biochemical and ra-diological studies. At all stages of observation, animals of group I were distinguished by relatively fast hea-ling times and restoration of physiological indicators and support on the operated limb. X-ray examination showed tight contact of bone tissue with the SiHA and formation of bone intermedial callus in the defect area. According to the hematological study, an increase in the indicators of biochemical markers of osteogenesis in animals with replenishment of the bone defect of the SiHA was monitored, which indicates active regeneration processes. The data obtained give reason to assume the effectiveness of using the SiHA to stimulate reparative regeneration in animals with bone pathologies.

Efficacy and safety of donepezil in patients with dementia with Lewy bodies: results from a 12-week multicentre, randomised, double-blind, and placebo-controlled phase IV study.

Donepezil has been approved in Japan for the treatment of dementia with Lewy bodies (DLB) based on clinical trials showing its beneficial effects on cognitive impairment. This phase IV study evaluated the efficacy of donepezil by focusing on global clinical status during a 12-week double-blind phase. Patients with probable DLB were randomly assigned to the placebo (n = 79) or 10 mg donepezil (n = 81) groups. The primary endpoint was changes in global clinical status, assessed using the Clinician's Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus). We also assessed four CIBIC-plus domains (general condition, cognitive function, behaviour, and activities of daily living) and changes in cognitive impairment and behavioural and neuropsychiatric symptoms measured using the Mini-Mental State Examination (MMSE) and the Neuropsychiatric Inventory (NPI), respectively. Although donepezil's superiority was not shown in the global clinical status, a significant favourable effect was detected in the cognitive domain (P = 0.006). MMSE scores improved in the donepezil group after adjustments in post hoc analysis (MMSE mean difference, 1.4 (95% confidence interval (CI), 0.42-2.30), P = 0.004). Improvements in NPIs were similar between the groups (NPI-2: -0.2 (95% CI, -1.48 to 1.01), P = 0.710; NPI-10: 0.1 (95% CI, -3.28 to 3.55), P = 0.937). The results support the observation that the efficacy of 10 mg donepezil in improving cognitive function is clinically meaningful in DLB patients. The evaluation of global clinical status might be affected by mild to moderate DLB patients enrolled in this study. No new safety concerns were detected.

Novel use of contrast enhanced ultrasonography with urodynamics in children: A comparison study to fluoroscopy.

Video urodynamics (UDS) has classically been performed using fluoroscopy (fluoro). Contrast enhanced voiding ultrasonography (ceVUS) has rarely been reported for use with UDS. This is the first study to compare the imaging characteristics of ceVUS versus fluoro UDS. Children were enrolled for ceVUS UDS who previously underwent fluoro UDS. Demographics, imaging data for ceVUS and fluoro UDS, time between studies, and clinical data between studies were recorded. Changes in clinical status included implantation/cessation of catheterization or anticholinergic medications, leakage between, urinary tract infections, hydronephrosis and neurologic changes. Comparison testing was performed using McNemar's Chi-Squared and Wilcoxon matched-pairs signed rank test. Seventy-five children were recruited. Median time between studies was 1.3 years (IQR 0.9-2.9). There were no differences for bladder shape (p = 0.59), vesicoureteral reflux (p = 0.10), bladder neck (p = 0.59) or urethra (p = 1.0) between studies. In 5 cases, the bladder neck could not be visualized adequately due to layering of the microbubble contrast against urine. Benefits to ceVUS included ability to visualize the exact moment the bladder neck opened. Following exclusion of patients with clinical changes that might affect imaging findings, an analysis of 28 patients demonstrated no differences between the two studies. CeVUS can be used adequately in conjunction with UDS. Limitations to ceVUS include more granular imaging for bladder shape versus fluoro and inability to visualize bladder neck if residual urine is in the bladder, mitigated by bladder emptying. Benefits include ability to visualize the dynamic activity of the bladder neck due to constant imaging with ceVUS.

The effects of Annual SZ drug on dynamic changes in lymphocytes and cytokines of COVID-19 patients: A randomized clinical trial

BackgroundThe search for a potent anti-coronavirus therapy has remained an overwhelming task since the outbreak of COVID-19. Annual SZ is a novel formulation of artemisinin and its derivatives. We aim to investigate the effect of Annual SZ on clinical outcomes, cellular immune responses, and cytokine changes in COVID-19 patients. MethodsThis study included 80 COVID-19 hospitalized patients, which were randomly allocated into two groups (intervention and control). Both groups received standard supportive treatment. In addition, the intervention group (n = 40) received Annual SZ syrup, and the control group (n = 40) received a placebo. Dynamic changes in lymphocytes, cytokines, and clinical status were evaluated since hospital admission to 7 and 14 days after treatment. ResultsThe dynamic count of total T lymphocytes and T lymphocyte subsets (CD4+ and CD8+) in the Annual SZ group was significantly higher than the placebo group (p < 0.05). In addition, Programmed Death 1 (PD-1) was significantly increased in the CD4+ and CD8+ T cells in the placebo group compared with the Annual SZ group (p < 0.05). Also, the CD4+/CD8+ ratio was not significantly different between the groups (p > 0.9). Moreover, IL-6 levels were significantly reduced (p < 0.05), while IL-4 and IFN-γ levels were not statistically different between the two groups (p > 0.05). ConclusionThis research indicated that the Annual SZ syrup significantly improved clinical status and lymphocyte frequency with less exhaustion of T lymphocytes and a reduction of inflammatory responses, which seems to be beneficial in the treatment process of COVID-19 patients.

P26 A life threatening case of Von Zumbusch psoriasis

Abstract We report a case of a patient admitted to intensive care with a pustulating skin eruption and haemodynamic compromise with near immediate response to infliximab. A 16-year-old male with a six-month history of mild plaque psoriasis presented to acute dermatology services with widespread annular pustular eruption, which developed days after a throat infection. Histopathology was consistent with pustular psoriasis. After an initial partial response, the pustules spread and persisted despite 2-month treatment with topical steroids and ciclosporin (dosed to 4 mg/kg). With raised inflammatory markers and repeated growth of Staphylococcus aureus, high dose intravenous flucloxacillin was administered. Four hours post infusion the patient became erythrodermic and haemodynamically unstable, requiring management in ICU. Repeat skin biopsy showed features of psoriasis without clear drug reaction features. Switching classes of antimicrobials and administration of intravenous immunoglobulins led to infection resolution but no significant clinical status change. A multi-disciplinary decision was made to trial intravenous infliximab. This resulted in near-immediate 90% improvement of skin and haemodynamic status. His excellent clinical response has been maintained on adalimumab thus far. Genetic screening for possible mutations associated with pustular psoriasis, including IL36RN and CARD14, are in process.