Acute Phase Research Articles

Who can benefit more from its twelve-week treatment: A prospective cohort study of blonanserin for patients with schizophrenia

BACKGROUND Blonanserin (BNS) is a well-tolerated and effective drug for treating schizophrenia. AIM To investigate which types of patients would obtain the most benefit from BNS treatment. METHODS A total of 3306 participants were evaluated in a 12-week, prospective, multicenter, open-label post-marketing surveillance study of BNS. Brief psychiatric rating scale (BPRS) scores were calculated to evaluate the effectiveness of BNS, and its safety was assessed with the incidence of adverse drug reactions. Linear regression was used to screen the influencing factors for the reduction of BPRS total score, and logistic regression was used to identify patients with a better response to BNS. RESULTS The baseline BPRS total score (48.8 ± 15.03) decreased to 27.7 ± 10.08 at 12 weeks (P < 0.001). Extrapyramidal symptoms (14.6%) were found to be the most frequent adverse drug reactions. The acute phase, baseline BPRS total score, current episode duration, number of previous episodes, dose of concomitant antipsychotics, and number of types of sedative-hypnotic agents were found to be independent factors affecting the reduction of BPRS total score after treatment initiation. Specifically, patients in the acute phase with baseline BPRS total score ≥ 45, current episode duration < 3 months, and ≤ 3 previous episodes derived greater benefit from 12-week treatment with BNS. CONCLUSION Patients in the acute phase with more severe symptoms, shorter current episode duration, fewer previous episodes, and a lower psychotropic drug load derived the greatest benefit from treatment with BNS.

Long-Term Cerebellar Consequences of Post-traumatic Brain Injury Assessed by MRI With Diffusion Tensor Imaging

BACKGROUND AND OBJECTIVES: Post-traumatic brain injury (TBI) lesions, which combine brain atrophy and white matter injuries, can lead to progressive post-traumatic encephalopathy. However, the specific involvement of the cerebellum, which participates in cognitive, executive, and sensory functions, has been little studied. The aim of this work was to explore the long-term cerebellar consequences of severe TBI. METHODS: In this retrospective study, patients included were hospitalized for a severe TBI and reassessed after discharge with a clinical examination and a MRI with diffusion tensor imaging. Patients were compared with a population of healthy volunteers. For a subgroup of this cohort, we analyzed the evolution of late post-TBI lesions on MRI up to 10 years after TBI. RESULTS: Ninety-seven patients reassessed 5 [3; 6] years after the TBI were included. Volume loss was revealed in the whole cerebellum (P = .01) and especially in the anterior lobe (P < .005) with a decrease in grey matter volume (P = 6.10−3). The mean diffusivity was increased in 4 cerebellar areas which are the right lower, right upper, left lower, and left upper cerebellar peduncles while the fractional anisotropy was decreased in all studied areas (P < 10−3). The longitudinal analysis (n = 17 patients) showed no progression of MRI lesions beyond the acute phase. CONCLUSION: This work shows that even if direct cerebellar damage is rare, long-term post-TBI cerebellar lesions can be observed. Therefore, clinical correlates of cerebellar lesions should be considered more systematically.

Abstract PR015: Sepsis-induced inflammation alters natural killer cell-mediated surveillance of liver metastasis

Abstract A majority of pancreatic ductal adenocarcinoma (PDAC) patients who undergo surgery for primary tumor resection will develop lethal metastases, despite having no evidence of metastasis at the time of their initial diagnosis. Liver metastases constitute nearly half of recurrences detected within the first six months following PDAC resection. Several clinical and experimental studies provide evidence that perioperative inflammation, including infectious complications like sepsis, positively correlates with liver metastasis across several malignancies. Despite these observations, it is still unknown whether there is a causal link between perioperative inflammation and PDAC liver metastasis. To gain mechanistic insight into the regulation of PDAC liver metastasis in the context of perioperative inflammation, we established mouse models that combine experimental PDAC liver metastasis with either the cecal ligation and puncture (CLP) model of polymicrobial sepsis or the lipopolysaccharide (LPS) model of acute sterile endotoxemia. Mice challenged with CLP prior to seeding PDAC cells in the liver had increased metastatic burden at endpoint compared to sham laparotomy controls. In contrast, mice challenged with LPS prior to PDAC cell seeding had reduced metastatic burden at endpoint compared to PBS-injected controls. We hypothesized that these opposing pro- and anti-metastatic effects of CLP and LPS, respectively, were due to qualitatively distinct inflammatory responses elicited in the liver. Our profiling of the host response to either CLP or LPS revealed shared systemic changes, including activation of the acute-phase protein response. However, LPS-associated inflammation uniquely upregulated a distinct set of interferon-regulated genes in the liver important for modifying immune cell activity (i.e., Ccl2, Ccl5, Cxcl9, Cxcl10). Accordingly, immunostaining and flow cytometry of the liver revealed that LPS uniquely increased the abundance of activated natural killer (NK) cells and MPO+ myeloid cells. We utilized Tlr4 -/- mice, which lack the primary receptor for LPS, to determine that the anti-metastatic effect of LPS required a host-facilitated response downstream of TLR4-mediated signaling. Through a series of genetic models and short-term depletion experiments, we determined that NK cells restrict PDAC cell seeding and outgrowth in our experimental liver metastasis model, and that this protective effect is further enhanced by activation of type-I interferon signaling in the host. Our findings confirm prior work identifying NK cell-mediated surveillance of disseminated cancer cells as an important mechanism in protecting against liver metastasis and show sterile endotoxemia and its associated inflammation establish a protective ‘anti-metastatic niche’ marked by enhanced NK cell activity. Further insights into the establishment of this niche may reveal potential therapeutic strategies to reduce the incidence of liver metastasis among resected PDAC patients. Citation Format: Nicole Sivetz, Patrick J. Cunniff, Christopher R. Vakoc, Semir Beyaz, Mikala Egeblad. Sepsis-induced inflammation alters natural killer cell-mediated surveillance of liver metastasis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr PR015.

Effects of Hyperbaric Oxygen Therapy in Treatment on Diverse Diseases

INTRODUCTION: Hyperbaric oxygen therapy (HBOT) indeed holds significant therapeutic potential across various medical conditions, primarily by increasing the concentration of oxygen delivered to tissues under pressure. Saturating tissues with oxygen allows for the effective alleviation of underlying hypoxia, facilitating healing, tissue repair and mechanisms of action leads to reducing concentration of pro-inflammatory acute phase proteins, interleukins, and cytokines. Conversely, HBOT while also boosting levels of growth factors and other cytokines that promote angiogenesis. REVIEW METHODS: The article was complied by analyzing data from PubMed and Google Scholar regarding effects of hyperbaric therapy. THE STATE OF KNOWLEDGE: Studies indicate that HBOT provides numerous opportunities in the treatment of extensive diseases acress various systems. Neurodegenerative disorders involve progressive nerve cell damage leading to motor or cognitive decline, exacerbated by oxidative stress and inflammation. HBOT has shown promise in delaying disease onset by improving mitochondrial dysfunction in motor neuron disease. In case of intestinal obstruction HBOT reduces intestinal gas volume, diameter of obstructed loops, and improves intestinal contractility. Significant benefits have been observed in conditions such as Crohn's disease and ulcerative colitis. Hyperbaric therapy presents potential benefits for the infertility, improving the environment for blastocyst implantation and pregnancy. CONCLUSION: There is no doubt that HBOT has a beneficial impact on treatment of many systems such as the nervous, cardiovascular, digestive, and skeletal. This innovative approach of hyperbaric therapy extends to selected disorders such as neurodegenerative diseases, Crohn's disease, ulcerative colitis, and infertility.

A multicenter, phase II trial of triplet antiemetic therapy with palonosetron, aprepitant, and olanzapine for highly emetogenic chemotherapy in breast cancer (PATROL-II).

Dexamethasone is an antiemetic drug widely used to prevent nausea and vomiting caused by anticancer drugs. However, dexamethasone can cause several side effects even after short-term administration. Therefore, the development of dexamethasone-free antiemetic therapies has been recognized as an important challenge. The objective of this study was to investigate the efficacy and safety of palonosetron, aprepitant, and olanzapine. Patients who were chemotherapy-naïve and scheduled to receive highly emetogenic chemotherapy for breast cancer were enrolled and assessed for nausea and vomiting occurring within 120h after the start of chemotherapy. The primary endpoint was the total control (TC) rate of overall phases. Secondary endpoints included the complete response (CR) rate, which was evaluated during the acute, delayed, and overall phases. A total of 88 patients were enrolled from eight centers in Japan, of whom 84 were included in the analysis. The proportion of patients achieving TC throughout the overall period was 17.1%. Similarly, CR and CC rates for the overall period were 43.4% and 39.5%, respectively. Frequently reported adverse events were loss of appetite and constipation, with rates of 52.4% and 50.0%, respectively. The primary endpoint was not achieved. Therefore, antiemetic therapy without dexamethasone shows an inadequate effect on nausea, and it is generally advisable to avoid omitting dexamethasone. However, in the overall period, both CR and CC were comparable to conventional three-drug combination therapy. Thus, in patients unable to use dexamethasone, replacing it with olanzapine could be an option.Trial registration number: UMIN 000038644, November 20, 2019. The date of first trial registration: 13/03/2020.

Inhibition of PCSK9 Protects against Cerebral Ischemia‒Reperfusion Injury via Attenuating Microcirculatory Dysfunction.

Proprotein convertase substilin/kexin type 9 (PCSK9), a pivotal protein regulating lipid metabolism, has been implicated in promoting microthrombotic formation and inflammatory cascades, thereby contributing to cardiovascular ischemia/reperfusion (I/R) injury. However, its involvement in cerebral I/R injury and its potential role in microcirculation protection remain unexplored. In this investigation, we utilized a middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model to simulate ischemic stroke. Different concentrations of evolocumab (1, 5, 10mg/kg, i.v.), a PCSK9 inhibitor, were administered to assess its impact. Immunofluorescence staining was employed to analyze changes in the expression of occludin, claudin-5, thrombocyte, ICAM-1, VCAM-1, and CD45, providing insights into blood-brain barrier integrity, platelet adhesion, and immune cell infiltration. Moreover, the Morris water maze and elevated plus maze were utilized to evaluate neurological and behavioral functions in MCAO/R mice, shedding light on the effects of PCSK9 inhibition. Our findings revealed a surge in plasma PCSK9 levels post-MCAO/R, peaking at 24h post-reperfusion. Evolocumab (10mg/kg) treatment significantly mitigated brain infarction and neurological deficits, evidenced by enhanced locomotor function and reduced post-stroke anxiety. However, it did not ameliorate cognitive impairment following MCAO/R. Additionally, evolocumab administration led to diminished leakage of evans blue solution and upregulated expression of occludin and claudin-5. Thrombocyte, ICAM-1, VCAM-1, and CD45 levels were notably reduced in the penumbral area post-evolocumab treatment. These protective effects are speculated to be mediated through the inhibition of the ERK/NF-κB pathway. The PCSK9 inhibitor evolocumab holds promise as a therapeutic agent during the acute phase of stroke, exerting its beneficial effects by modulating the ERK/NF-κB signaling pathway.

An Overview of Randomized Controlled Trials Examining Prescription and Nonprescription Pharmacological Interventions for Moderate to Severe Traumatic Brain Injury

Objective: To characterize randomized controlled trials (RCTs) of pharmacological interventions (prescription medications, nonprescription medications, and supplements) for the management of moderate to severe traumatic brain injury (MSTBI). Data sources: Systematic searches were conducted in MEDLINE, PubMed, Scopus, CINAHL, EMBASE, and PsycINFO for RCTs up to December 2022 inclusive in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Study selection and data extraction: Inclusion criteria were RCT study design; participants’ mean age ≥ 18 years and ≥ 50% had MSTBI; examined ≥ 1 pharmacological intervention(s), either alone or in combination with other interventions. Two independent reviewers conducted Cochrane risk of bias assessment. Data synthesis: Three hundred thirteen RCTs (1978-2022) met inclusion criteria. A total of 146 unique pharmacotherapies and supplements were studied. The most frequently studied intervention was mannitol ( n = 20 RCTs). Mean sample size was 230.4 (4-12 737) and 195 studies (62.3%) were conducted in the acute phase post-MSTBI. Four hundred thirty-five unique outcome measures (OMs) were studied; the most common OMs used were Glasgow Outcome Scale (GOS) (29.4%), mortality (25.2%), and intracranial pressure (25.2%), Glasgow Coma Scale (GCS) (19.5%), and mean arterial pressure (17.3%), and heart rate (10%). Of the included studies, only 7% ( n = 22) had low risk of bias. Conclusion: The paucity of high-quality studies, variability in RCT methodology, sample sizes, and OMs utilization, as well as the low number of RCTs conducted in the subacute- and chronic-phase after injury pose a challenge for conducting meta-analyses to provide strong recommendations for informed decision-making in clinical practice.

The prevalence and clinical correlation factors of cognitive impairment in patients with major depressive disorder hospitalized during the acute phase

ObjectiveThis study aimed to investigate the prevalence of cognitive impairment among patients with major depressive disorder (MDD) hospitalized during the acute phase and to analyze the in-depth association between this cognitive impairment and clinical correlation factors.MethodsIn this cross-sectional study, we recruited 126 patients aged between 18 and 65 years who were diagnosed with MDD. All these patients were inpatients from the Department of Psychiatry at the Second People’s Hospital of Hunan Province. We employed a series of assessment tools, including the Pittsburgh Sleep Quality Index (PSQI), the 16-item Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS-16), the Pre-sleep Arousal Scale (PSAS), the Morningness-Eveningness Questionnaire (MEQ), the Hamilton Anxiety Rating Scale (HAMA), and the 17-item Hamilton Depression Rating Scale (HAMD-17). The patients were divided into a cognitive impairment group and a non-cognitive impairment group based on their scores on the Montreal Cognitive Assessment Scale (MoCA). Through Spearman’s correlation analysis, we explored the correlation between the total MoCA score and the score of each factor. Additionally, we utilized binary logistic regression analysis to investigate the relationship between cognitive impairment and clinically relevant factors in MDD patients hospitalized during the acute phase and plotted ROC curves to evaluate their clinical efficacy.ResultsIn this study, we found that the prevalence of cognitive impairment among MDD patients hospitalized during the acute phase was as high as 63.49%. Through statistical analysis, we observed significant differences between the cognitive impairment group and the non-cognitive impairment group in terms of age, place of residence, education level, and HAMD-17 scores. In the Spearman correlation analysis, we noted the following trends: visuospatial and executive abilities were negatively correlated with the HAMD-17 score (P < 0.05); naming ability was positively correlated with the PSAS score but negatively correlated with the MEQ score (P < 0.05); memory was also negatively correlated with the MEQ score (P < 0.05); attention was negatively correlated with the HAMA score; and abstract cognitive ability was negatively correlated with the MEQ score (P < 0.05). Through binary logistic regression analysis, we further revealed the relationship between cognitive impairment and factors such as living in a rural area (OR = 2.7, 95% CI = 1.083-6.731, P < 0.05), increased age (OR = 1.049, 95% CI = 1.013-1.087, P < 0.01), and the HAMD-17 score (OR = 1.10295, 95% CI = 1.031-11.79, P < 0.01). Additionally, ROC curve analysis demonstrated a significant correlation between the HAMD-17 score and the prediction of cognitive function in MDD patients hospitalized during the acute phase (P < 0.001). Specifically, the AUC for the HAMD-17 score was 0.73, with an optimal cut-off value of 19.5, sensitivity of 70.0%, and specificity of 63.0%. Furthermore, the AUC for age was 0.71, with an optimal cut-off value of 33.5, sensitivity of 59.0%, and specificity of 80.0%.ConclusionsThis study indicates that MDD patients hospitalized during the acute phase have a higher prevalence of cognitive impairment. This phenomenon reflects a significant correlation between clinical factors such as age, sleep-related characteristics, and the severity of depression with cognitive impairment. Therefore, regular assessment of cognitive function in MDD patients and early intervention may be crucial for the treatment and prognosis of the disease.

Functional Outcome Prediction of Acute Ischemic Stroke Based on the Oral and Gut Microbiota.

Although several studies have identified a distinct gut microbiota in individuals with acute ischemic stroke (AIS), there is a limited amount of research that has simultaneously investigated alterations in the oral and intestinal microbiota in AIS patients and their correlation with clinical prognosis. This was a prospective and observational single-center cohort study in which we included 160 AIS patients who were admitted within 24h after a stroke event. We collected oral and rectal swab samples for analysis using 16S rRNA high-throughput sequencing. Our study revealed that patients with unfavorable outcomes after AIS showed early disruptions in their oral and intestinal microbiota. Rectal swabs showed increased levels of facultatively anaerobic bacteria in patients with a poor prognosis, while the oral cavity exhibited higher levels of anaerobic and opportunistic pathogenic bacteria. By employing machine learning analysis, we found that the microbiota composition at both rectal and oral sites could predict early and long-term outcomes. Moreover, patients with a poor prognosis displayed increased oral bacterial colonization in the rectal microbiota and altered interactions between the oral and gut microbiota. This study reveals distinct rectal and oral bacteria that could predict unfavorable outcomes for AIS patients. Monitoring the microbiota of various body sites during the early stages after admission may hold prognostic value and inform personalized treatment strategies. The presence of oral bacteria colonizing the intestines during the acute phase of stroke could serve as an early indication of poor outcomes for AIS patients.

Different antithrombotic strategies to prevent cardiovascular complications in Kawasaki patients: a systematic review and meta-analysis.

Coronary artery aneurysm (CAA) poses significant cardiovascular risks, particularly in Kawasaki disease (KD) patients. This systematic review and meta-analysis aim to evaluate and compare antithrombotic strategies in preventing CAA formation secondary to Kawasaki disease and the ensuing CAA cardiovascular complications. Following PRISMA guidelines, we systematically searched major databases, namely PubMed, Scopus, Web of Science, and Embase. Major adverse cardiovascular events (MACE), myocardial infarction (MI), stenosis, bleeding, occlusion, and coronary artery lesion (CAL) formation were primary outcomes. Consolidated Standards of Reporting Trials (CONSORT) and Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) scores assessed study quality. A meta-analysis, as well as sensitivity analysis and meta-regression, was performed to compare the efficacy of pharmacological strategies on the outcomes. The study included 21 studies with 1045 patients for CAA complications and 41536 patients for CAA formation prevention. In children with CAA secondary to Kawasaki disease, the addition of warfarin to aspirin was associated with a significantly lower odds of myocardial infarction (OR = 0.26, 95% CI: 0.11-0.60, I2 = 25%) and mortality (OR = 0.18, 95% CI: 0.04-0.88, I2 = 0%) compared to aspirin alone. However, there was no significant difference in MACE (OR = 0.38, 95% CI: 0.08-1.93, I2 = 60%) and occlusion (OR = 0.17, 95% CI: 0.02-1.92, I2 = 58%). Sensitivity analysis showed reduced thrombosis (OR = 0.29, 95% CI: 0.14-0.62, I2 = 0%), MACE (OR [95% CI] = 0.22[0.06-0.84], I2 = 46%), and occlusion (OR [95% CI] = 0.08[0.02-0.44], I2 = 36%). Meta-regression did not yield significant results. As for the acute phase of KD, no benefit was conferred from adding high-dose aspirin to the routine IVIG alone regimen. However, the complexity of outcomes and the diversity in antithrombotic interventions underscore the need for tailored approaches and further research.

Epicardial Lead Performance Trends in Pediatric and Congenital Heart Disease.

Background: Epicardial pacing systems, rather than transvenous systems, are utilized in pediatric patients who are too small to undergo transvenous access and/or have complex congenital heart disease (CHD) anatomically precluding a transvenous system. Longitudinal performance studies indicate that epicardial leads have higher failure rates when compared with transvenous leads but there are limited data on lead measurement changes in the acute phase after implantation. The objective of this study was to assess epicardial lead performance in the acute postimplant period and at one-year follow-up. Methods: This is a retrospective single center study of children and adult patients with CHD undergoing epicardial bipolar pacing lead and generator implantation between January 2012 and June 2022. We empirically selected 2 V as a critical lead threshold. Results: There were 256 leads implanted in 127 patients (mean age 6.1 ± 9.8 years), including 201/256 (79%) leads in patients with CHD. At the time of implant, 47/256 leads (18%) had a lead threshold of ≥2 V. Of those, 42 of 47 (89%) had recorded threshold values on postoperative day 1 (POD1) and 37 of 42 (88%) had decreased to a more acceptable threshold that was <2 V. For patients with an implant threshold of ≥2 V; impedance >1000 ohms, presence of CHD, perioperative or acute postop status, and location of the lead (atrial vs ventricular) did not significantly impact the odds of having a persistently high threshold (≥2 V) on POD1. Conclusion: Epicardial pacing lead thresholds generally improve in the immediate postop period and in our experience most leads with a high implant threshold improved to <2 V by POD1.

Antemortem diagnostic tests for the detection of Aspergillus infection in birds: a systematic review.

Aspergillosis remains a common and life-threatening disease in captive and wild birds all over the world. Diagnosis is currently based on clinical signs or lesions, diagnostic imaging and a variety of biological tests. This systematic review aimed to compare the accuracy of antemortem diagnostic tests for Aspergillus infection in birds. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a search was conducted on PubMed, Scopus, Web of Science, CAB until January 2024. The methodological quality was assessed with QUADAS 2 risk of bias tool. The thirteen studies, selected for the review, included results from a wide variety of birds (mainly Spheniciformes but also Falconiformes, Psittaciformes, and Galliformes) from wildlife rehabilitation centers, zoological parks or veterinary practices. Aspergillus infection was mainly confirmed by fungal culture and/or histopathology. Serum markers included Aspergillus components (galactomannan, ß-D-glucan, mannoproteins and gliotoxin), anti-Aspergillus antibodies, 3-hydroxybutyrate as well as protein electrophoresis and acute phase molecules. Sensitivity and specificity displayed a large amount of variation despite threshold arrangement. Disparities in the number of individuals per study did not allow for reliable comparison. Platelia Ag Assay (Bio-Rad), the most commonly used test in the studies, demonstrated moderate specificity and low sensitivity. Overall, non-specific tests demonstrated more consistent performance, whereas specific tests showed greater variability. Based on current knowledge, none of these tests provide sufficient accuracy to reliably detect Aspergillus infection in birds in clinical practice.

Poor semen quality is associated with impaired antioxidant response and acute phase proteins and is likely mediated by high cortisol levels in Brucella-seropositive dromedary camel bulls.

Brucellosis in dromedary camel bulls leads to either temporary or permanent loss of fertility. Camel brucellosis is associated with both orchitis and epididymitis. However, the clinical signs of camel brucellosis are not clear as those in cattle. Therefore, this study aimed to diagnose camel brucellosis based on a serological screening using Rose Bengal plate test (RBPT) followed by competitive ELISA. To understand the impact of brucellosis on camel bull fertility, this study aimed to examine the semen characteristics, evaluate the testicular histopathology, examine hormonal profile, antioxidants and acute phase proteins (APP). A total of 150 mature bulls were used in this study. Blood samples were collected for serological, hormonal, and biochemical analysis. This study revealed that 6.6% and 7.3% of the examined bulls were Brucella-seropositive using RBPT and competitive ELISA, respectively. The Brucella-seropositive dromedary bulls showed poor semen quality, pathological changes orchitis, and lower testosterone. Moreover, our findings showed a higher cortisol level, and significant impairments in the measured APP and antioxidants in Brucella-seropositive bulls. In conclusion, the Brucella-seropositive dromedary bulls showed lower fertility due to poor semen quality and lower testosterone levels. Such lower fertility is likely mediated by high cortisol levels, and impaired APP and antioxidants' defense response.

Chronic Spontaneous Urticaria—New Predictor on the Horizon?

Chronic urticaria is one of the most common diseases in allergology and dermatology practice with unclear causes of occurrence. Background: Some studies emphasize the correlation between inflammation in chronic urticaria and disturbed intestinal microbiota. It raises the question about the role of some intestine-related substances in the pathogenesis of urticaria as well as their potential role as disease predictors. Calprotectin is an acute-phase protein with a well-established diagnostic position in the field of gastroenterology. There are some data on the relationship between this parameter and gut microbiota. The major aim of this preliminary study is to investigate whether calprotectin can be potentially taken into account as a disease course predictor in urticaria. Methods: We included in our study 54 chronic spontaneous urticaria (CSU) patients (of whom 26 manifested the symptoms of recurrent angioedema) and 29 patients allergic to Hymenoptera venom for the reference group (in these patients, before venom immunotherapy induction, full diagnostics is performed including intestinal problems). Disease activity in the CSU patients was assessed using the Urticaria Activity Score (UAS) and the disease control in this group was assessed with the Urticaria Control Test (UCT). Moreover, we analyzed fecal and serum calprotectin concentrations. Results: Positive correlation was found only between the values of serum calprotectin concentration and the control level of CSU symptoms with the lack of other relations. Conclusions: Our results do not supply unequivocal evidence for calprotectin as a potential marker of CSU course, though this concept, in the light of growing evidence for microbiota’s role in urticaria, requires further research.

Longitudinal 1H NMR-Based Metabolomics in Saliva Unveils Signatures of Transition from Acute to Post-Acute Phase of SARS-CoV-2 Infection

COVID-19 can range from a mild to severe acute respiratory syndrome and also could result in multisystemic damage. Additionally, many people develop post-acute symptoms associated with immune and metabolic disturbances in response to viral infection, requiring longitudinal and multisystem studies to understand the complexity of COVID-19 pathophysiology. Here, we conducted a 1H Nuclear Magnetic Resonance metabolomics in saliva of symptomatic subjects presenting mild and moderate respiratory symptoms to investigate prospective changes in the metabolism induced after acute-phase SARS-CoV-2 infection. Saliva from 119 donors presenting non-COVID and COVID-19 respiratory symptoms were evaluated in the acute phase (T1) and the post-acute phase (T2). We found two clusters of metabolite fluctuation in the COVID-19 group. Cluster 1, metabolites such as glucose, (CH3)3 choline-related metabolites, 2-hydroxybutyrate, BCAA, and taurine increased in T2 relative to T1, and in cluster 2, acetate, creatine/creatinine, phenylalanine, histidine, and lysine decreased in T2 relative to T1. Metabolic fluctuations in the COVID-19 group were associated with overweight/obesity, vaccination status, higher viral load, and viral clearance of the respiratory tract. Our data unveil metabolic signatures associated with the transition to the post-acute phase of SARS-CoV-2 infection that may reflect tissue damage, inflammatory process, and activation of tissue repair cascade. Thus, they contribute to describing alterations in host metabolism that may be associated with prolonged symptoms of COVID-19.

Animal models of Long Covid: A hit-and-run disease.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2) pandemic has caused more than 7 million deaths globally. Despite the presence of infection- and vaccine-induced immunity, SARS-CoV-2 infections remain a major global health concern because of the emergence of SARS-CoV-2 variants that can cause severe acute coronavirus disease 2019 (COVID-19) or enhance Long Covid disease phenotypes. About 5 to 10% of SARS-CoV-2-infected individuals develop Long Covid, which, similar to acute COVID 19, often affects the lung. However, Long Covid can also affect other peripheral organs, especially the brain. The causal relationships between acute disease phenotypes, long-term symptoms, and involvement of multiple organ systems remain elusive, and animal model systems mimicking both acute and post-acute phases are imperative. Here, we review the current state of Long Covid animal models, including current and possible future applications.

COMPLEX PHYSICAL THERAPY OF PATIENTS WITH ADHESIVE CAPSULITIS

Adhesive capsulitis is predominantly an idiopathic condition and is more common in patients with metabolic disorders. PS contracture can be of varying degrees of severity, depending on the pathology of the PS with which we are dealing. This condition greatly aff ects work capacity and quality of life due to the presence of pain, discomfort and limitation of daily life activities. Prolonged pain syndrome can provoke sleep disorders and depression. Disruption of normal sleep, pain and depression form a pathological closed circle and contribute to the maintenance of the pathological process in the locus morbi.The development of a comprehensive program of physical therapy for patients with adhesive capsulitis with the use of modern means of recovery, which will reduce the risk of the disease re-emerging, and will also contribute to the faster recovery of the functional capacity of the musculoskeletal system of the patients.The objective of the study. The develop and practically substantiate a comprehensive program of therapy for patients with adhesive capsulitis using physical therapy.Materials and Research Methods. The study is based on a comprehensive therapeutic approach for 36 patients diagnosed with adhesive capsulitis in the acute phase of the condition. The assessed parameters included X-ray and computed tomography results, evaluation of range of motion in the shoulder joint, joint- muscle apparatus, and analysis of pain intensity indicators.Conclusions. To improve the condition of patients and optimize the process of treatment and rehabilitation of patients with adhesive capsulitis of the shoulder joint in the acute period, it is advisable to use with the diff erentiation of means of therapeutic intervention according to the diagnosis of the international classifi cation of functioning, optimization of physiotherapeutic means and special means of physical therapy allowed to shorten the terms of treatment and recovery of patients with adhesive capsulitis. It was determined that the best combination of means of therapeutic intervention for patients with adhesive capsulitis is the use of a complex of ideomotor exercises to create the patient’s idea of correct movement; correct positioning of the limb during sleep, everyday and professional activity; passive exercises to increase the volume of painless movements (bending, external rotation); restorationof the pattern of typical motor actions and optimization of physiotherapeutic means due to the use of shock wave and TENS therapy signifi cantly improved the eff ectiveness of their recovery in the short-term and long-term stages of the acute period of rehabilitation.

EGS SO28 - Management of oesophageal diverticulitis in a 71-year-old female: Case report and review of management approaches

Abstract Background Oesophageal diverticulitis is a rare condition with fewer than ten reports in the literature. We present a case of oesophageal diverticulitis in a 71-year-old female with a history of COPD, TIA, and known oesophageal diverticulum. She was managed conservatively with NBM, total parenteral nutrition and intravenous antibiotics requiring a 16-day inpatient stay. The rarity of this condition poses challenges in its diagnosis and management, necessitating a thorough understanding of both conservative and surgical interventions. This case highlights the complexity involved in treating oesophageal diverticulitis, especially in patients with significant comorbidities. Method Patient presented with a 6-day history of upper abdominal pain and sepsis (elevated inflammatory markers; CRP 320, WCC 11.1, temperature 38.0, pulse 104). Abdomen was soft with upper abdominal tenderness. Imaging was consistent with diverticulitis of a 5.9cm lower oesophageal diverticulum without perforation. Initial management included making the patient nil by mouth, total parenteral nutrition, and intravenous antibiotics (vancomycin and metronidazole). The patient’s condition was closely monitored with serial blood tests and clinical assessments. Opinion was sought from a tertiary upper GI centre. Discharge was planned once the patient safely transitioned to oral diet and was apyrexial for 48 hours. Results Inflammatory markers improved over five days (CRP from 320 to 51, WCC from 11.1 to 9). She remained intermittently pyrexial until day 8 of admission. Clinical improvement allowed transition from intravenous to oral therapy, and she was discharged on day 16 with double dose oral PPI therapy. Patient has been followed up by tertiary upper GI services with plans for consideration of surgical resection of the oesophageal diverticulum. The patient’s successful discharge without surgical intervention during the acute phase underscores the effectiveness of a conservative management approach initially, with a plan for definitive surgical treatment in a stable outpatient setting. Conclusion Oesophageal diverticulitis, though rare, requires a nuanced approach to management, especially in patients with significant comorbidities. This case demonstrates the importance of an awareness of thorough history taking and review of previous examinations to prevent delayed diagnosis of a rare pathology not demonstrated on a CT abdomen and pelvis. This approach highlights the importance of individualised treatment plans and the potential for conservative management to provide stabilisation, followed by elective surgical management. The paucity of cases of oesophageal diverticulitis has prevented development of evidence based guidelines, underscoring the importance of seeking advice from tertiary centers when managing rare presentations.

Translating insights into therapies for Long Covid.

Long Covid is defined by a wide range of symptoms that persist after the acute phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Commonly reported symptoms include fatigue, weakness, postexertional malaise, and cognitive dysfunction, with many other symptoms reported. Symptom range, duration, and severity are highly variable and partially overlap with symptoms of myalgic encephalomyelitis/chronic fatigue syndrome and other post-acute infectious syndromes, highlighting opportunities to define shared mechanisms of pathogenesis. Potential mechanisms of Long Covid are diverse, including persistence of viral reservoirs, dysregulated immune responses, direct viral damage of tissues targeted by SARS-CoV-2, inflammation driven by reactivation of latent viral infections, vascular endothelium activation or dysfunction, and subsequent thromboinflammation, autoimmunity, metabolic derangements, microglial activation, and microbiota dysbiosis. The heterogeneity of symptoms and baseline characteristics of people with Long Covid, as well as the varying states of immunity and therapies given at the time of acute infection, have made etiologies of Long Covid difficult to determine. Here, we examine progress on preclinical models for Long Covid and review progress being made in clinical trials, highlighting the need for large human studies and further development of models to better understand Long Covid. Such studies will inform clinical trials that will define treatments to benefit those living with this condition.

The Role of High-Resolution Ultrasound in the Diagnosis of Nerve Trauma New Perspective: A Preliminary Systematic Review and Meta-Analysis of the Recent Evidence.

Precise localization of peripheral nerve injuries and evaluation of their prognosis based on clinical and electrodiagnostic examinations are particularly challenging in the acute phase. High-resolution ultrasound (HRUS) may offer a viable and cost-effective imaging option for assessing the morphology of nerve injuries. Consequently, a systematic review and meta-analysis of studies on the use of ultrasound for diagnosing traumatic nerve injuries were conducted. A total of 15 studies were included, reporting the most recent findings on using HRUS in the diagnosis of traumatic nerve injury. These studies assessed the diagnostic test accuracy of ultrasound for the detection of traumatic nerve injury in 272 participants, with the cross-sectional area at the site of traumatic nerve injury also reported in 1,249 participants. The pooled sensitivity and specificity of the included studies were 92% confidence interval (CI) (0.89-0.95) and 86% CI (0.82-0.89), respectively. The positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 13.76 CI (1.41-134.34), 0.08 CI (0.03-0.18), and 286.23 CI (21.22-3,860.40), respectively. In the summary of the receiver operating characteristic curve, the area under the curve was 0.986, and the Q* index was 0.949. Based on the current literature, HRUS has shown promising results in addition to its availability and feasibility. HRUS can serve as a valuable complement to clinical and electrodiagnostic examinations for diagnosing traumatic peripheral nerve injuries. Further research is recommended to better understand the ultrasound characteristics of these injuries.