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Abstract The gut microbiome is a significant factor in the pathophysiology of ulcerative colitis (UC), prompting investigations into the use of probiotic therapies to counter gastrointestinal inflammation. However, while much attention has been given to the therapeutic potential of microbes at the species and strain level, the discovery and application of their metabolic products may offer more precise and controlled solutions in battling disease. In this work, we examined the therapeutic potential of indole lactic acid (ILA) to alleviate inflammation in a murine model of colitis. A previously constructed ILA-producing Escherichia coli Nissle 1917 strain (EcN aldh) and its isogenic non-ILA producing counterpart (EcN) were studied in a murine model of Dextran Sodium Sulfate (DSS) induced colitis. The colitic animals suffered from severe colitic symptoms, with no differentiation between the groups in body weight loss and disease activity index. However, three days after cessation of DSS treatment the EcN aldh–treated mice showed signs of reduced intestinal inflammation, as manifested by lower concentrations of fecal lipocalin-2. Additionally, expression analysis of the inflamed tissue revealed distinct effects of the EcN aldh strain on proteins associated with intestinal health, such as TFF3, occludin and IL-1β expression. These results show no impact of EcN or EcN aldh on acute DSS-induced colitis, but suggest that in particular EcN aldh may assist recovery from intestinal inflammation.

Apart from providing user-friendly applications that support digitized healthcare routines, the use of wearable devices has proven to increase the independence of patients in a healthcare setting. By applying machine learning techniques to real health-related data, important conclusions can be drawn for unsolved issues related to disease prognosis. In this paper, various machine learning techniques are examined and analyzed for the provision of personalized care to COVID-19 patients with mild symptoms based on individual characteristics and the comorbidities they have, while the connection between the stimuli and predictive results are utilized for the evaluation of the system’s transparency. The results, jointly analyzing wearable and electronic health record data for the prediction of a daily dyspnea grade and the duration of fever, are promising in terms of evaluation metrics even in a specified stratum of patients. The interpretability scheme provides useful insight concerning factors that greatly influenced the results. Moreover, it is demonstrated that the use of wearable devices for remote monitoring through cloud platforms is feasible while providing awareness of a patient’s condition, leading to the early detection of undesired changes and reduced visits for patient screening.

Abstract Background Kinetic and kinematic gait analysis is increasingly practised as a part of lameness evaluation in dogs. The aim of this study was to examine the normal short- and long-term variation in forelimb gait in sound control dogs (CD) at a walk using seven selected variables of objective kinetic and kinematic gait analyses. Also, to compare the findings in CD to a group of forelimb lame dogs with elbow osteoarthritis (OAD). An additional aim was to test a kinetic based graphic method for lameness detection; symmetry squares (SS). A prospective longitudinal study was carried out on client owned CD and OAD. Clinical and orthopaedic evaluations were performed to ensure soundness and detect and grade lameness. Seven kinetic and kinematic variables and SS were tested for lameness evaluation. The CD were divided into two subgroups, CD1 and CD2, and examined twice: CD1 with two months interval and CD2 with 3–4 h interval. The OAD group was evaluated once and compared to the CD groups’ first examination. Results Thirteen CD and 19 OAD were included. For CD1 and CD2, there were no significant differences in any examined variable between examination occasions. Total peak force/impulse symmetry and fore-hind peak force/impulse symmetry differed significantly between OAD and CD. Symmetry squares had a 74% agreement to subjective orthopaedic evaluations. Conclusions In CD, no difference in the examined variables was seen between examination occasions. Four out of seven objective variables differed significantly between CD and OAD. The graphic SS method might have diagnostic potential for lameness detection, making it possible to detect a shift from lame to non-lame limbs. Potentially, this might be especially helpful in bilaterally lame dogs, which often represent a clinical challenge in lameness evaluation.

George Mangouritsas, Spyridon Mourtzoukos, Dimitra M Portaliou, Vassilios I Georgopoulos, Anastasia Dimopoulou, Elias Feretis Eye Clinic, General Hospital "Hellenic Red Cross", Athens, Greece Abstract: Transient or permanent elevation of intraocular pressure (IOP) is a common complication following vitreoretinal surgery. Usually secondary glaucoma, which develops after scleral buckling procedures, or pars plana vitrectomy for repair of rhegmatogenous retinal detachment, is of multifactorial origin. It is essential, for appropriate management, to detect the cause of outflow obstruction. An exacerbation of preexisting open-angle glaucoma or a steroid-induced elevation of IOP should also be considered. Scleral buckling may be complicated by congestion and anterior rotation of the ciliary body resulting in secondary angle closure, which can usually resolve with medical therapy. The use of intravitreal gases may also induce secondary angle-closure with or without pupillary block. Aspiration of a quantity of the intraocular gas may be indicated. Secondary glaucoma can also develop after intravitreal injection of silicone oil due to pupillary block, inflammation, synechial angle closure, or migration of emulsified silicone oil in the anterior chamber and obstruction of the aqueous outflow pathway. In most eyes medical therapy is successful in controlling IOP; however, silicone oil removal with or without concurrent glaucoma surgery may also be required. Diode laser transscleral cyclophotocoagulation and glaucoma drainage devices constitute useful treatment modalities for long-term IOP control. Cooperation between vitreoretinal and glaucoma specialists is necessary to achieve successful management. Keywords: retinal detachment, intraocular pressure elevation, glaucoma, vitrectomy, intravitreal gas, silicone oil

Background: Adenoviral vector COVID-19 vaccine-induced immune thrombotic thrombocytopenia (VITT) is a heparin-independent platelet-activating disorder. An increasing number of VITT-like disorders without previous vaccination are being identified. Key Clinical Question: To explore the association of the pediatric cluster of postinfectious thrombosis and thrombocytopenia with VITT-like disorders. Clinical Approach: Three children with severe thrombocytopenia, coagulopathy, elevated D-dimer, and thrombotic events (cerebral venous sinus thrombosis) were reported. Two had positive nasopharyngeal samples for adenovirus, and 1 had group A streptococcus infection. They all had a COVID-19 history and low-risk antiphospholipid syndrome. Heterozygosity for factor V Leiden was found in 2 children. In 2 patients for whom anti–platelet factor 4 (PF4) serology was performed, positive results were found by PF4/polyanion lateral-flow immunoassay but negative results by PF4/polyanion chemiluminescence immunoassay. All patients were treated with enoxaparin or fondaparinux and intravenous immunoglobulin, while 3 received platelets transfusion and steroids. Conclusion: This cluster of pediatric cases with thrombosis and thrombocytopenia may indicate a postinfectious (most notably, postadenovirus) VITT-like disorder.

ObjectiveCritically ill patients, including those with brain injuries (BI), are frequently hospitalized in an intensive care unit (ICU). As with other critical states, an adequate stress response is essential for survival. Research on the hypothalamic-pituitary-adrenal gland (HPA) axis function in BI has primarily focused on assessing ACTH and cortisol levels. However, the immunological, metabolic, and hemodynamic effects of glucocorticoids (GCs) are mediated through the glucocorticoid receptor (GCR), a ubiquitously distributed intracellular receptor protein. Data on GCR-α expression and its signaling in acute BI injury are lacking.MethodsWe designed a prospective observational study, carried out in one academic multi-disciplinary ICU. Forty-two critically ill patients with acute (BI)were included. These patients suffered from traumatic BI (N= 20), subarachnoid hemorrhage (N= 12), intracranial hemorrhage (N= 7), or ischemic stroke (N= 3). All patients were steroid-free. Twenty-four age and sex-matched healthy controls were used for comparison.ResultsExpression of GCR-α and the glucocorticoid-inducible leucine zipper (GILZ), serum cortisol, interleukins (IL) 6, 8, 10 and TNF- α, and the BI biomarkers glial fibrillary acidic protein (GFAP) and total Tau were measured on ICU admission (within 48 hours) and 5-7 days from admission. Compared to healthy controls, in the critically ill patients with BI, GCR-α mRNA expression was significantly downregulated on admission, and after 5-7 days in the ICU (2.3-fold, p

Objective: This meta-analysis aimed to assess the prevalence of respiratory viruses among children under the special conditions of the COVID-19 pandemic. Methods: Five databases were systematically searched to assess the pooled prevalence of various respiratory viruses in different age groups, regions, seasons, and in patients with and without confirmed SARS-CoV-2 coinfection. Moreover, we looked at the virus distribution in the first and second half of the pandemic and countries with distinct economic status. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed, and the systematic review was registered on PROSPERO (CRD42022379297). Results: Enterovirus/rhinovirus and human respiratory syncytial virus (HRSV) were the most prevalent pathogens among children. The prevalence of HRSV increased in the second half of the pandemic. The prevailing viruses vary according to the SARS-CoV-2-coinfection status, season, region, and country´s economic status. Conclusion: This meta-analysis shows the epidemiology of respiratory viruses other than SARS-CoV-2 in children aged 0 to 12 years during the COVID-19 pandemic. Because major events, such as a pandemic, can alter epidemiology patterns, it is important to know them to improve health education measures, develop vaccines and medicines for vulnerable groups, as a guide for prevention strategies, and help with clinical decisions.

OBJECTIVES:. Optimal timing of tracheostomy in severe traumatic brain injury (TBI) is unknown due to lack of clinical trials. We emulated a target trial to estimate the effect of early vs. delayed tracheostomy strategy on functional outcome of patients with severe TBI. DESIGN:. Target trial emulation using 1:1 balanced risk-set matching. SETTING:. North American hospitals participating in the TBI Hypertonic Saline randomized controlled trial of the Resuscitation Outcomes Consortium. PATIENTS:. The prematching population consisted of patients with TBI and admission Glasgow Coma Scale less than or equal to 8, who were alive and on mechanical ventilation on the fourth day following trial enrollment, and stayed in the ICU for at least 5 days. Patients with absolute indication for tracheostomy and patients who died during the first 28 days with a decision to withdraw care were excluded. INTERVENTIONS:. We matched patients who received tracheostomy at a certain timepoint (early group) with patients who had not received tracheostomy at the same timepoint but were at-risk of tracheostomy in the future (delayed group). The primary outcome was a poor 6-month functional outcome, defined as Glasgow Outcome Scale-Extended less than or equal to 4. MEASUREMENTS AND MAIN RESULTS:. Out of 1282 patients available for analysis, 275 comprised the prematching population, with 75 pairs being created postmatching. Median time of tracheostomy differed significantly in the early vs. the delayed group (7.0 d [6.0–10.0 d] vs. 12.0 d [9.8–18.3 d]; p < 0.001). Only 40% of patients in the delayed group received tracheostomy. There was no statistically significant difference between groups regarding poor 6-month functional outcome (early: 68.0% vs. delayed: 72.0%; p = 0.593). CONCLUSIONS:. In a target trial emulation, early as opposed to delayed tracheostomy strategy was not associated with differences in 6-month functional outcome following severe TBI. Considering the limitations of target trial emulations, delaying tracheostomy through a “watchful waiting” approach may be appropriate.

Abstract Background The complement system is an important arm of immune defense bringing innate and adaptive immunity. Although originally regarded as a major complementary defense mechanism against pathogens, continuously emerging evidence has uncovered a central role of this complex system in several diseases including lung pathologies. Main body Complement factors such as anaphylatoxins C3a and C5a, their receptors C3aR, C5aR and C5aR2 as well as complement inhibitory proteins CD55, CD46 and CD59 have been implicated in pathologies such as the acute respiratory distress syndrome, pneumonia, chronic obstructive pulmonary disease, asthma, interstitial lung diseases, and lung cancer. However, the exact mechanisms by which complement factors induce these diseases remain unclear. Several complement-targeting monoclonal antibodies are reported to treat lung diseases. Conclusions The complement system contributes to the progression of the acute and chronic lung diseases. Better understanding of the underlying mechanisms will provide groundwork to develop new strategy to target complement factors for treatment of lung diseases.

Abstract Introduction The aim was to assess the performance of a blood assay combining measurements of MxA (myxovirus resistance protein A) and CRP (C-reactive protein) to differentiate viral from bacterial respiratory infections. Methods In a prospective study, MxA and CRP were measured in the blood by the AFIAS panel in adults admitted with respiratory infection. Patients were split into discovery and validation cohorts. Final diagnosis was adjudicated by a panel of experts. Microbiology-confirmed cases comprised the discovery cohort, and infections adjudicated as highly probable viral or bacterial comprised the validation cohort. Results A total of 537 patients were analyzed: 136 patients were adjudicated with definitive viral infections and 131 patients with definitive bacterial infections. Using logistic regression analysis, an equation was developed to calculate the probability for bacterial infection using the absolute value of MxA and CRP. Calculated probability ≥ 0.5 and/or MxA to CRP ratio less than 2 applied as the diagnostic rule for bacterial infections. This rule provided 91.6% sensitivity and 90.4% negative predictive value for the diagnosis of bacterial infections. This diagnostic sensitivity was confirmed in the validation cohort. A MxA/CRP ratio less than 0.15 was associated with unfavorable outcome. Conclusion The calculation of the probability for bacterial infection using MxA and CRP may efficiently discriminate between viral and bacterial respiratory infections.

According to the WHO, more than 90,000 cases of mpox have been reported since the 2022 worldwide outbreak, which resulted in 167 deaths, while a new outbreak in Africa since 2023 has resulted in over 18,000 cases and 617 deaths. Mpox is a zoonosis caused by the monkeypox virus, a double-stranded DNA virus belonging to the Orthopoxvirus genus, which causes smallpox-like illness. Until 2022, cases were predominately located in West and Central Africa, with only sporadic cases and outbreaks reported in other parts of the world. During the 2022 outbreak, the primary mode of transmission was sexual contact among men who have sex with men. The changing epidemiology of mpox resulted in new disease phenotypes and populations at risk, disproportionally affecting people who live with HIV. Commonly presenting as a mild, self-limiting illness, mpox can cause severe and protracted disease in people with HIV with a CD4 count < 200 cell/mm3. The global emergence of mpox that followed and intersected with COVID-19 mobilized the scientific community and healthcare stakeholders to provide accurate diagnostics, preventive vaccines and treatment to those most affected. Despite existing gaps, this rapid response helped to contain the outbreak, but challenges remain as new variants emerge. Preparedness and readiness to respond to the next outbreak is crucial in order to minimize the impact to the most vulnerable.

Objective: Sex-specific data are limited regarding eligibility for hypolipidemic treatment. We aim to explore the sex-specific clinical utility of high-sensitivity C-reactive protein (hsCRP) and carotid ultrasound as risk modifiers for hypolipidemic treatment in primary prevention of atherosclerotic cardiovascular disease (ASCVD). Methods: We aimed to explore these sex-specific trends in two pooled contemporary independent Greek cohorts (Athens Vascular Registry n = 698, 50.9% women and Menopause Clinic n = 373, 100% women) of individuals without overt ASCVD. Baseline ASCVD risk was estimated using the Systematic COronary Risk Evaluation-2 (SCORE2) tools. The presence of carotid plaque and hsCRP ≥2 mg/L were integrated as risk modifiers. Results: Men had increased odds to achieve target LDL-C levels based on ASCVD risk (23.8% vs. 17.7%, OR: 1.45 95% CI: 1.05–2.00, p = 0.023, for men vs. women). Additionally, considering carotid plaque or high hsCRP levels did not change this association but reduced on-target LDL-C rate in both sexes. Women had decreased odds of being eligible for hypolipidemic treatment by ASCVD risk estimation (11.5% vs. 26.4%, p

Primary melanoma of the duodenum is an extremely rare, aggressive and life-threatening malignant neoplasm. Published data regarding the effectiveness of current treatment strategies is limited, and our knowledge relies mostly on sporadic case reports. The diagnosis of primary duodenal melanoma is challenging and is based on the patient’s medical history and findings from physical examination and radiological and endoscopic imaging as well as proper and careful pathological examinations of the tumor. Despite the many advances in cancer treatment, the prognosis for patients with this type of melanoma remains extremely poor. Delayed diagnosis at advanced disease stage, the general aggressive behavior of this neoplasm, the technical difficulty in achieving complete surgical resection, along with the rich vascular and lymphatic drainage of the intestinal mucosa, all have a negative impact on patients’ outcome. In the present review, we aimed to collect and summarize the currently available data in the literature regarding the pathogenesis, clinical features, diagnosis, management and long-term outcomes of this rare, malignant tumor, in order to expand knowledge of its biological behavior and investigate optimal therapeutic options for these patients. Additionally, we present our experience of a case involving a 73-year-old female with primary duodenal melanoma, who was successfully treated with complete surgical resection.

Background: The cardiac toxicity of chemotherapy for breast cancer is not uncommon and has been associated with elevated morbidity and mortality. In the present study, we assessed the impact of chemotherapy on cardiovascular function by assessing the cardio–ankle vascular index (CAVI), global longitudinal strain (GLS) and ventricular–arterial coupling (VAC: CAVI/GLS ratio) in chemotherapy-treated women. Methods: This prospective study enrolled 78 women with breast cancer who were receiving anthracycline-based chemotherapy +/− anti-HER2 therapy (trastuzumab +/− pertuzumab). Forty-one age-matched healthy women served as controls. We comparatively evaluated left ventricular ejection fraction (LVEF), CAVI, GLS and VAC, between the chemotherapy and control groups. We also assessed their changes over time (baseline, 3-month and 6-month time point) and their independent association with the incidence of cancer therapy-related cardiovascular dysfunction (CTRCD) in the chemotherapy group. Results: In comparison to healthy controls, women receiving chemotherapy presented with significantly higher GLS (from −21.02 ± 2.09% to −19.01 ± 2.81%, p < 0.001) and VAC (−0.36 ± 0.06 to −0.41 ± 0.11, p < 0.001). The presence of CTRCD was associated with a further increase in GLS and CAVI and a significant decline in LVEF and VAC compared to CTRCD-free women (p < 0.001). Baseline, CAVI, GLS and VAC were independently associated with CTRCD development during follow-up. Conclusion: Women with breast cancer undergoing chemotherapy displayed abnormal levels of CAVI, VAC and GLS, compared to healthy individuals. Those effects on VAC and CAVI were more exaggerated among women with CTRCD, implicating their potential use to refine screening and therapeutic strategies for this specific population.

We aimed to determine the diagnostic yield and outcome of patients receiving antithrombotic drug therapy subjected to small bowel capsule endoscopy (SBCE) for the investigation of small bowel bleeding (SBB). A multicenter retrospective analysis of collected data from all patients undergoing SBCE for the investigation of SBB from March 2003 to June 2023 was performed. The diagnostic yield of SBCE was defined as the detection of positive findings that could explain the cause of the patient’s bleeding. Rebleeding was defined as evidence of bleeding within 1 year after the index episode. During the study period, 8401 patients underwent SBCE for SBB investigation. Bleeding lesions were detected in 1103/2535 (43.5%) antithrombotic users, compared to 1113/5866 (18.9%) in nonusers (p < 0.00001). Following capsule endoscopy, a therapeutic intervention was possible in 390/2216 (17.5%) patients with a bleeding lesion. Rebleeding occurred in 927 (36.5%) of antithrombotic users (36.5%), compared to 795 (13.5%) of nonusers (13.5%, p < 0.00001). Both the diagnostic yield of SBCE and the rebleeding rates were higher in patients with SBB receiving antithrombotics. Therapeutic intervention was possible in a real-world setting only for a minority of patients with positive findings.