Resolution Of Disease Research Articles

Antibiotics in the non-surgical treatment of peri-implantitis.

Four electronic databases (MEDLINE via Pubmed; EMBASE via Ovid; EBSCO Dentistry and Oral Science Source), in addition to six related journals (Clinical Implant Dentistry and Related Research; Clinical Oral Implants Research; International Journal of Oral and Maxillofacial Implants; International Journal of Oral Implantology; Journal of Clinical Periodontology; Journal of Periodontology), were searched for publications until 2022. Randomised controlled trials (RCTs), evaluating the effectiveness of local or systemic antibiotics as an adjunct in the non-surgical treatment (NST) for peri-implantitis (PI), were assessed. The eligibility criteria included RCTs with a parallel group, split-mouth design and appropriate NST interventions over a three to twelve month period. Data were extracted from RCTs to capture a multitude of primary outcomes, including: implant success rate, radiographic marginal bone loss rate, periodontal health changes and PI resolution. Risk of bias assessments were made using the Cochrane Collaboration's tool, by two authors independently and in duplicate. RCTs with similar observation periods and interventions were included in the meta-analyses. Random-effects meta-analyses of mean differences or relative risks with 95% confidence intervals were calculated, in additional to data heterogeneity calibration through I2 statistics. Following the screening of 270 papers, six RCTs were included, which resulted in the evaluation of 391 patients (375 implants). Adjunctive local antibiotic therapy at disease sites showed statistically significant periodontal outcomes; improvements in success rate (risk ratio = 9.89; 95% CI 2.39-40.84), probing pocket depth (mean difference (MD) = 0.6 mm; 95% CI 0.42-0.78) and bleeding on probing (MD = 0.15%; 95% CI 0.10-0.19). Conversely, adjunctive systemic antibiotics improved probing pocket depths (MD = 1.15 mm; 95% CI 0.31-1.99) and probing attachment levels only (MD = 1.10 mm; 95% CI 0.13-2.08). Across the six included RCTs, the bone loss rate and PI resolution rate determined no significant differences between the groups; mirrored in the single studies and in the meta-analysis. Disease resolution ranged from 2 to 65%. Two of the studies were found to be at low risk of bias and four presented with some concerns. Adjunctive antibiotics aid NST. However, the heterogeneity of study methods and low quality of current RCTs evidenced, deem their role in NSTs of PI as inconclusive.

Sex effects on gingival transcriptomic patterns during initiation, progression, and resolution of periodontitis.

The prevalence and severity of periodontitis demonstrates altered population distribution with age, sex, and race and ethnicity. While males exhibit greater frequency of disease, particularly with aging, the underlying basis for this observation remains obscure. This study used a nonhuman primate (Macaca mulatta) model of experimental ligature-induced periodontitis in adult animals to evaluate gingival transcriptomic differences stratified based upon sex of the animal. The 18 animals represented humans ages 40-80 years, with gingival tissue samples obtained at baseline, 0.5 months (initiation), 1 and 3 months (progression), and at 5 months that were 60 days after ligature removal for clinical disease resolution. Microarray analysis was used to quantify gene expression profiles in the gingival tissues. The results demonstrated clear gene expression differences in healthy (baseline) tissues between the sexes, with elevations in females associated with immune responses and elevation in males related to tissue structural genes. With disease initiation, fewer genes differed between the sexes, while these differences were significantly increased in progressing disease and resolution, particularly in male animals. Overexpressed biological processes showed tissue structural/functional genes at initiation, with host response pathways altered during disease progression. Resolution samples generally demonstrated biological processes of cellular metabolism that differed from baseline healthy samples. The transcriptomic findings support sex as a biological variable in periodontitis using a nonhuman primate model of experimental periodontitis.

Efficacy of Sleeve Gastrectomy with Concomitant Hiatal Hernia Repair versus Sleeve-Fundoplication on Gastroesophageal Reflux Disease Resolution: Systematic Review and Meta-Analysis.

(1) Background: There is still disagreement over how sleeve gastrectomy (SG) affects gastroesophageal reflux disease (GERD). The debate regarding the best option for patients undergoing bariatric surgery who are also affected by GERD and/or hiatal hernia continues to divide the community of bariatric surgeons. While concomitant hiatal hernia repair (SG + HHR) has been proposed as a means of reducing the risk of GERD following SG with varying degrees of success, the addition of a fundoplication (SG + FP) has been suggested in recent years as a way to improve the lower esophageal sphincter's competency. The aim of this study is to systematically review and meta-analyze the efficacy of SG + HHR versus SG + FP on GERD remission in patients with obesity. (2) Methods: A systematic review of the literature was conducted, and studies analyzing the effects of SG + HHR versus SG + FP on postoperative GERD were included. The methodological quality of included trials was evaluated. The primary outcome was postoperative GERD rate, erosive esophagitis, and 12-month weight loss. Secondary outcomes included postoperative complications and mortality. The PRISMA guidelines were used to carry out the present systematic review (PROSPERO Registration Number: CRD42023405600). (3) Results: Fifteen articles with a total of 1164 patients were included in the meta-analysis; 554 patients underwent SG + HHR while 610 underwent SG + FP. In the SG + HHR group, 58.5 ± 28.9% of subjects presented clinical GERD symptoms compared to 20.4 ± 17.5% postoperatively (p < 0.001). In the SG + FP group, 64.8 ± 39.4% were affected by GERD preoperatively compared to only 5 ± 8.1% postoperatively (p < 0.001). SG + FP patients had a significantly greater GERD remission compared to SG + HHR (p < 0.001). Weight loss was similar between groups (p = 0.125). The rate of leaks was 0.18% and 0.33% in the SG + HHR and SG + FP, respectively (p = 0.657), while perforations were significantly higher after SG + FP compared to the SG + HHR group (3.1% versus 0%, p = 0.002). The mortality rate was significantly greater in the SG + FP group (0.5% versus 0%, p = 0.002). (4) Conclusions: This study revealed that both SG with concomitant HHR and sleeve-fundoplication are effective in terms of reflux resolution and weight outcomes, with superiority of SG + FP in terms of GERD control, despite a greater overall complication rate. Both strategies can therefore be suggested as a suitable alternative variant to a conventional SG in subjects with obesity and concomitant hiatal hernia and/or GERD. Studies with extended follow-up and direct comparisons of these surgical approaches to conventional SG are warranted.

Abstract 712: IL-19 Is A Lymphokine That Induces Prox1-dependent Lymphangiogenesis And Permeability

Introduction: Atherosclerosis is a vascular inflammatory disease associated with lymphangiogenesis, but whether lymphangiogenesis contributes to disease progression or is simply a compensatory attempt at disease resolution is currently unresolved. Recent studies are revealing a role for lymphatic vessels in reverse cholesterol transport (RCT), which could attenuate atherosclerosis. We have previously reported that Interleukin-19 (IL-19), an anti-inflammatory cytokine, uniquely attenuates atherosclerotic plaque progression while also being pro-angiogenic. This drives our hypothesis that one mechanism whereby IL-19 is atheroprotective is by promoting functional lymphangiogenesis and lymphatic flux. Methods &amp; Results: IL-19 can significantly induce human dermal lymphatic endothelial cell (hdLEC) proliferation, migration, and tube formation, to the same degree as VEGFC, a potent inducer of lymphangiogenesis. RNA sequencing analysis indicates that IL-19 induces an angiogenic transcriptional program through Prox1, a master regulator of lymphangiogenesis. Knockdown of Prox1 led to a significant decrease in IL-19-associated proliferation and migration. IL-19 also increased expression of Angpt2, an endothelial cell protein that induces permeability through regulation of tight junctions, through a Prox1-dependent mechanism. Electric Cell-substrate Impedance Sensing assays showed that IL-19 treatment increased hdLEC permeability and mitigated oxLDL-associated decreased permeability, suggestive of maintaining lymphatic barrier function during atherosclerosis. IL-19 treatment also increased dil-HDL transport across an hdLEC barrier. Preliminary in vivo data suggests injection of rmIL-19 in Il19 -/- mice increases lymphatic permeability and flux through increased lymphatic uptake of Evans blue dye. Conclusion: These data suggest that IL-19 increases lymphangiogenesis, permeability, and may increase RCT to plausibly decrease atherosclerosis. These results can influence our understanding of the association between the lymphatic system and atherosclerosis.

TLRs: Innate Immune Sentries against SARS-CoV-2 Infection.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been responsible for a devastating pandemic since March 2020. Toll-like receptors (TLRs), crucial components in the initiation of innate immune responses to different pathogens, trigger the downstream production of pro-inflammatory cytokines, interferons, and other mediators. It has been demonstrated that they contribute to the dysregulated immune response observed in patients with severe COVID-19. TLR2, TLR3, TLR4 and TLR7 have been associated with COVID-19 severity. Here, we review the role of TLRs in the etiology and pathogenesis of COVID-19, including TLR7 and TLR3 rare variants, the L412F polymorphism in TLR3 that negatively regulates anti-SARS-CoV-2 immune responses, the TLR3-related cellular senescence, the interaction of TLR2 and TLR4 with SARS-CoV-2 proteins and implication of TLR2 in NET formation by SARS-CoV-2. The activation of TLRs contributes to viral clearance and disease resolution. However, TLRs may represent a double-edged sword which may elicit dysregulated immune signaling, leading to the production of proinflammatory mediators, resulting in severe disease. TLR-dependent excessive inflammation and TLR-dependent antiviral response may tip the balance towards the former or the latter, altering the equilibrium that drives the severity of disease.

B lymphocytes in COVID-19: a tale of harmony and discordance.

B lymphocytes play a vital role in the human defense against viral infections by producing specific antibodies. They are also critical for the prevention of infectious diseases by vaccination, and their activation influences the efficacy of the vaccination. Since the beginning of coronavirus disease 2019 (COVID-19), which became the main concern of the world health system, many efforts have been made to treat and prevent the disease. However, for the development of successful therapeutics and vaccines, it is necessary to understand the interplay between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, and the immune system. The innate immune system provides primary and nonspecific defense against the virus, but within several days after infection, a virus-specific immune response is provided first by antibody-producing B cells, which are converted after the resolution of disease to memory B cells, which provide long-term immunity. Although a failure in B cell activation or B cell dysfunction can cause a severe form of the disease and also lead to vaccination inefficiency, some individuals with B cell immunodeficiency have shown less production of the cytokine IL-6, resulting in a better disease outcome. In this review, we present the latest findings on the interaction between SARS-CoV-2 and B lymphocytes during COVID-19 infection.

Efficacy of ruxolitinib for HAVCR2 mutation-associated hemophagocytic lymphohistiocytosis and panniculitis manifestations in children.

Frequent germline mutations of HAVCR2, recently identified in subcutaneous panniculitis-like T-cell lymphoma (SPTCL), are associated with an increased risk of hemophagocytic lymphohistiocytosis (HLH). However, SPTCL-HLH represents a challenge because of the difficulties in treatment with poor survival. Its malignant nature, specifically harbouring HAVCR2 mutations, has also been questioned. To better understand its pathology and treatment, we analysed the clinical data of six patients diagnosed at our centre. The median age at onset was 10.5 years (range, 0.8-12.4). Five patients presented with skin lesions of subcutaneous nodules/plaques and/or ulceration. All patients developed HLH; notably, one infant only had HLH without skin involvement. Histopathologically, only two patients were diagnosed with SPTCL and three were reported as panniculitis with no sufficient evidence of lymphoma. Genetically, germline homozygous mutation of HAVCR2 (p.Y82C) was identified in all patients, with a median diagnosis time of 4.6 months. All patients initially received corticosteroids, immunosuppressants or chemotherapy, achieving unfavourable responses. Strikingly, they responded well to ruxolitinib targeting inflammatory cytokines, allowing rapid disease resolution and/or long-term maintenance of remission. The excellent efficacy of ruxolitinib highlights this disease as an inflammatory condition instead of neoplastic nature and indicates novel agents targeting key inflammatory pathways as an encouraging approach for this disease entity.

Temporal tracking of microglial and monocyte single-cell transcriptomics in lethal flavivirus infection

As the resident parenchymal myeloid population in the central nervous system (CNS), microglia are strategically positioned to respond to neurotropic virus invasion and have been implicated in promoting both disease resolution and progression in the acute and post-infectious phase of virus encephalitis. In a mouse model of West Nile virus encephalitis (WNE), infection of the CNS results in recruitment of large numbers of peripheral immune cells into the brain, the majority being nitric oxide (NO)-producing Ly6Chi inflammatory monocyte-derived cells (MCs). In this model, these cells enhance immunopathology and mortality. However, the contribution of microglia to this response is currently undefined. Here we used a combination of experimental tools, including single-cell RNA sequencing (scRNA-seq), microglia and MC depletion reagents, high-dimensional spectral cytometry and computational algorithms to dissect the differential contribution of microglia and MCs to the anti-viral immune response in severe neuroinflammation seen in WNE. Intriguingly, analysis of scRNA-seq data revealed 6 unique microglia and 3 unique MC clusters that were predominantly timepoint-specific, demonstrating substantial transcriptional adaptation with disease progression over the course of WNE. While microglia and MC adopted unique gene expression profiles, gene ontology enrichment analysis, coupled with microglia and MC depletion studies, demonstrated a role for both of these cells in the trafficking of peripheral immune cells into the CNS, T cell responses and viral clearance. Over the course of infection, microglia transitioned from a homeostatic to an anti-viral and then into an immune cell-recruiting phenotype. Conversely, MC adopted antigen-presenting, immune cell-recruiting and NO-producing phenotypes, which all had anti-viral function. Overall, this study defines for the first time the single-cell transcriptomic responses of microglia and MCs over the course of WNE, demonstrating both protective and pathological roles of these cells that could potentially be targeted for differential therapeutic intervention to dampen immune-mediated pathology, while maintaining viral clearance functions.

SUPERFICIAL CERVICAL LYMPHADENITIS ASSOCIATED WITH STREPTOCOCCUS PHOCAE IN FIVE COMMON BOTTLENOSE DOLPHINS (TURSIOPS TRUNCATUS): A CASE SERIES.

Between 2009 and 2018, five common bottlenose dolphins (Tursiops truncatus) at the US Navy Marine Mammal Program presented with superficial cervical lymphadenitis. Clinical findings included ultrasonographic evidence of cervical lymph node enlargement, severe leukocytosis, elevated erythrocyte sedimentation rates, and reduced serum iron. Three of the dolphins presented with clinicopathologic changes without presence of clinical signs, and the other two cases additionally presented with partial to complete anorexia, lethargy, and refusal to participate in training sessions. Ultrasound-guided fine needle aspiration or biopsy of the affected lymph nodes yielded Streptococcus phocae by PCR in all cases, and the organism was cultured in one of five cases. Animals were treated with a combination of enteral, parenteral, intralesional antimicrobial, or a combination of those therapies and supportive care. Time to resolution of clinical disease ranged between 62 and 188 days. To the authors' knowledge, this is the first report of Streptococcus phocae cervical lymphadenitis in cetaceans. Streptococcus phocae lymphadenitis should be a differential for cervical lymphadenopathy in this species, especially when associated with pronounced systemic inflammation and a history of potential exposure.

Experience of successful treatment of a patient with chronic non-bacterial osteomyelitis (clinical case)

BACKGROUND: Chronic nonbacterial osteomyelitis is a rare autoinflammatory bone disease with periods of relapses and remissions. No etiotropic therapy, diagnostic and treatment standards exist, patients are observed by rheumatologists, immunologists, and orthopedist. They receive symptomatic, anti-inflammatory treatment, broad-spectrum antibiotics, immunosuppressants to control inflammation, which helps to prevent new or to reduce existing pathological foci.&#x0D; CLINICAL CASE DESCRIPTION: This article describes the effect of immune therapy and osteotropic treatment with zoledronic acid combination in a patient with chronic non-bacterial osteomyelitis. In a clinical observation involving comprehensive examination, including radiological (radiography, computed tomography and magnetic resonance imaging) and laboratory methods, a positive outcome was achieved using conservative methods of treatment in a patient with chronic non-bacterial sternum osteomyelitis.&#x0D; CONCLUSION: Thus, a combination of bisphosphonates and immunotherapy may be promising in the treatment of chronic non-bacterial osteomyelitis. However, it is unknown as to how long the remission will last and what treatment program is necessary for the final disease resolution.

The efficacy of implant surface decontamination using chemicals during surgical treatment of peri-implantitis: A systematic review and meta-analysis.

To answer the following PICOS question: "In adult patients with peri-implantitis, what is the efficacy of surgical therapy with chemical surface decontamination of implant surfaces in comparison with surgical therapy alone or surgery with placebo decontamination, on probing pocket depth (PD) reduction and bleeding on probing (BoP)/suppuration on probing (SoP), in randomized controlled clinical trials (RCTs) and non-RCTs with at least 6months of follow-up?" Six databases were searched from their inception up to 20 May 2022. Data on clinical outcome variables were pooled and analysed using mean differences (MDs), risk ratios (RRs), or risk differences (RDs) as appropriate, 95% confidence intervals (CIs), and prediction intervals (PIs) in the case of significant heterogeneity. Primary outcomes were determined as changes in PD and BoP/SoP. Secondary outcomes were radiographic marginal bone loss (MBL), implant loss, and disease resolution. PROSPERO registration number: CRD42022325603. Six RCTs-two with moderate, three with high, and one with low risk of bias (RoB)-were included. These studies test the adjunctive effect of photodynamic therapy (PDT), chlorhexidine (CHX), and administration of local antibiotics (LAbs) during surgery on the clinical outcome. In a single 12-month study, the adjunctive use of local antibiotics showed a clinically relevant reduction of PD [MD=1.44; 95%CI (0.40 to -2.48)] and MBL [MD=1.21; 95%CI (0.44-1.98); one trial, 32 participants]. PDT showed a small but significant reduction in BoP [MD=7.41%; 95%CI (0.81-14.00); p= 0.028; two trials; 42 participants]. Treatment with CHX resulted in no significant changes in PD, BoP, or MBL compared to placebo (saline solution). None of the interventions affected disease resolution and implant loss. Certainty of the evidence was very low for all outcome measures assessed. Within the limitations of this systematic review and the meta-analysis, adjunctive use of chemicals such as PDT, CHX, and LAbs for surface decontamination during surgery of peri-implantitis cannot be recommended as superior to standard debridement procedures (mechanical debridement with or without saline).

Efficacy of Intravitreal Anti Vascular Endothelial Growth Factor Injection Compared to Focal Therapy in Pediatric Patients with Coats Disease

Introduction: Coats disease is a retinal vascular disorder that may lead to progressive exudative retinal detachment. The standard regiment of treatment is focal therapy. However, its effectiveness may decrease when more than two quadrants of the retina exhibit vascular abnormalities. Thus, recent studies tried to use anti vascular endothelial growth factor (anti-VEGF) as therapy for the vascular problems. Aims: Comparing the efficacy between anti-VEGF injection and standard therapy regiment such as focal laser therapy. Methods: Literature searching was conducted through PubMed, ScienceDirect, Google Scholar, ProQuest, and SpringerLink. Search terms included "Coats’ Disease" and mesh terms of “Anti- VEGF". The efficacy is assessed based on Best-Corrected Visual Acuity (BCVA) and improvement in fundus manifestations. Results: All of the studies that conducted primary intravitreal anti-VEGF treatment were followed by necessary ablative treatment. These studies, such as by Yang Q and Zheng XX, et al. showed remarkable improvements in both visual acuity and anatomical outcomes. Laser therapy also gained satisfactory result in upgrading clinical stages, even though some complications including subretinal fibrosis, cataract, and vitreous hemorrhage were reported. A comparative study by Ray R, et al. noted that group undergoing anti-VEGF might require longer treatment sessions despite possible benefits. Conclusion: Anti-VEGF agents can be used as neoadjuvant in standard therapy. It did not reduce the time for full treatment, but the resolution of disease was seen in the most severe cases treated with combination therapy.

Gut and airway microbiota dysbiosis and their role in COVID-19 and long-COVID.

The gut microbiota plays a crucial role in human health and disease. Gut dysbiosis is known to be associated with increased susceptibility to respiratory diseases and modifications in the immune response and homeostasis of the lungs (the so-called gut-lung axis). Furthermore, recent studies have highlighted the possible role of dysbiosis in neurological disturbances, introducing the notion of the "gut-brain axis." During the last 2 years, several studies have described the presence of gut dysbiosis during coronavirus disease 2019 (COVID-19) and its relationship with disease severity, SARS-CoV-2 gastrointestinal replication, and immune inflammation. Moreover, the possible persistence of gut dysbiosis after disease resolution may be linked to long-COVID syndrome and particularly to its neurological manifestations. We reviewed recent evidence on the association between dysbiosis and COVID-19, investigating the possible epidemiologic confounding factors like age, location, sex, sample size, the severity of disease, comorbidities, therapy, and vaccination status on gut and airway microbial dysbiosis in selected studies on both COVID-19 and long-COVID. Moreover, we analyzed the confounding factors strictly related to microbiota, specifically diet investigation and previous use of antibiotics/probiotics, and the methodology used to study the microbiota (α- and β-diversity parameters and relative abundance tools). Of note, only a few studies focused on longitudinal analyses, especially for long-term observation in long-COVID. Lastly, there is a lack of knowledge regarding the role of microbiota transplantation and other therapeutic approaches and their possible impact on disease progression and severity. Preliminary data seem to suggest that gut and airway dysbiosis might play a role in COVID-19 and in long-COVID neurological symptoms. Indeed, the development and interpretation of these data could have important implications for future preventive and therapeutic strategies.

Efficacy of adjunctive measures in peri-implant mucositis. A systematic review and meta-analysis.

To answer the following PICO question: In systemically healthy humans with peri-implant mucositis, what is the efficacy of patient-performed or administered (by prescription) measures used adjunctively to submarginal instrumentation, as compared to submarginal instrumentation alone or combined with a negative control, in terms of reducing bleeding on probing (BOP), in randomized controlled clinical trials (RCTs) with at least 3 months of follow-up? Three databases were searched until April 2022. Weighted mean differences (WMDs) with 95% confidence intervals (CIs) and predictive intervals were calculated. Sixteen parallel RCTs corresponding to 14 studies with low/moderate risk of bias were included. Test groups showed greater reductions in BOP (%) than control groups (nstudies =16; npatients =650; WMD=14.25%; 95% CI [9.06-19.45]; p < .001; I2 = 98.7%). The greatest WMD in BOP reductions (%) were obtained by antiseptics (ns =5; np =229; WMD=22.72%; 95% CI [19.40-26.04]; p < 0.001; I2 = 94.8%), followed by probiotics (ns =6; np =260; WMD=12.11%; 95% CI [3.20-21.03]; p=.008; I2 = 93.3%) and systemic antibiotics (ns =3; np =101; WMD=5.97%; 95% CI [1.34-10.59]; p=.012; I2 = 58.1%). Disease resolution was scarcely reported (n=6). Significant clinical improvements can be obtained when professional submarginal instrumentation is combined with patient-performed or administered (by prescription) adjunctive measures, although a complete disease resolution may not be achieved.

Outcome indicators of non-surgical therapy of peri-implantitis: a prospective case series analysis.

This study aims to identify patient and implant indicators influencing the non-surgical therapeutic outcomes of peri-implantitis at 6months of follow-up. This case series involved patients with at least one implant diagnosed with peri-implantitis according to the 2017 World Workshop criteria. Non-surgical therapy consisted of mechanical debridement of the peri-implant pockets combined with metronidazole 500mg 3 times a day for 7days. At baseline and at 6months, clinical and radiographic variables were collected to calculate treatment success (probing pocket depth reduction to 5mm without bleeding on probing or < 5mm irrespective of bleeding on probing at all implant sites, and lack of bone loss progression). The primary outcome was treatment success (%) at 6months. The influence of the patient and implant/prosthetic variables upon disease resolution was assessed through simple and multiple logistic regression analyses at patient and implant level, using generalized estimation equations models. A total of 74 patients and 107 implants were analyzed at 6months. Disease resolution was established in 25.7% of the patients and 24.1% of the implants. Patients with stage IV and grade C periodontitis, inadequate oral hygiene at baseline, and wide diameter (≥ 4.5mm) presented significantly greater treatment failure, whereas smokers and former smokers demonstrated a tendency toward failure. At 6months, there was a significant decrease in probing pocket depth and bleeding on probing of 1.08 ± 1.06mm and 14%, respectively. Radiographically, a significant gain in marginal bone level of 0.43 ± 0.56mm was observed. Disease resolution after non-surgical treatment of peri-implantitis is negatively influenced by the loss of support of the adjacent periodontium, poor baseline oral hygiene, and wide diameter implants (≥ 4.5mm). This study helps to discriminate the clinical situations in which non-surgical treatment is less likely to achieve treatment success at short term.

Lifestyle modification in the treatment of refractory gastroesophageal reflux disease and non-alcoholic fatty liver disease. A clinical case

The article presents a clinical case of refractory gastroesophageal reflux disease (GERD) in a female patient with non-alcoholic fatty liver disease and morbid obesity. A 38-year-old woman came to the clinic with complaints of heartburn up to 5–6 times a day, other manifestations of pain and dyspeptic syndromes. Morbid obesity, refractory GERD with erosive esophagitis, and hepatic steatosis were diagnosed during follow-up examination. A set of treatment measures was developed, which included lifestyle modification, proton pump inhibitors and ursodeoxycholic acid preparations. During the observation period of 16 months, a gradual decrease in body weight was accompanied by a decrease in the frequency of heartburn. As a result, the patient lost 49kg. During the control instrumental examination, a positive trend was observed in terms of sonographic and endoscopic indicators, as well as a decrease in liver stiffness according to elastography data. A review of the literature on the correlation between obesity, steatosis and reflux disease is given. Conclusion. Obesity and related fatty liver disease can be additional factors for the development of refractory GERD, and a significant reduction in body weight leads to both resolution of reflux disease and improvement of parameters characterizing the structural state of the liver.

Elevated plasma interleukin-8 as a risk factor for mortality in children presenting with cerebral malaria

BackgroundCerebral malaria (CM) is a neuropathology which remains one of the deadliest forms of malaria among African children. The kinetics of the pathophysiological mechanisms leading to neuroinflammation and the death or survival of patients during CM are still poorly understood. The increasing production of cytokines, chemokines and other actors of the inflammatory and oxidative response by various local actors in response to neuroinflammation plays a major role during CM, participating in both the amplification of the neuroinflammation phenomenon and its resolution. In this study, we aimed to identify risk factors for CM death among specific variables of inflammatory and oxidative responses to improve our understanding of CM pathogenesis.MethodsChildren presenting with CM (n = 70) due to P. falciparum infection were included in southern Benin and divided according to the clinical outcome into 50 children who survived and 20 who died. Clinical examination was complemented by fundoscopic examination and extensive blood biochemical analysis associated with molecular diagnosis by multiplex PCR targeting 14 pathogens in the patients’ cerebrospinal fluid to rule out coinfections. Luminex technology and enzyme immunoassay kits were used to measure 17 plasma and 7 urinary biomarker levels, respectively. Data were analysed by univariate analysis using the nonparametric Mann‒Whitney U test and Pearson’s Chi2 test. Adjusted and multivariate analyses were conducted separately for plasma and urinary biomarkers to identify CM mortality risk factors.ResultsUnivariate analysis revealed higher plasma levels of tumour necrosis factor (TNF), interleukin-1beta (IL-1β), IL-10, IL-8, C-X-C motif chemokine ligand 9 (CXCL9), granzyme B, and angiopoietin-2 and lower urinary levels of prostanglandine E2 metabolite (PGEM) in children who died compared to those who survived CM (Mann–Whitney U-test, P-values between 0.03 and < 0.0001). The multivariate logistic analysis highlighted elevated plasma levels of IL-8 as the main risk factor for death during CM (adjusted odd ratio = 14.2, P-value = 0.002). Values obtained during follow-up at D3 and D30 revealed immune factors associated with disease resolution, including plasma CXCL5, C–C motif chemokine ligand 17 (CCL17), CCL22, and urinary 15-F2t-isoprostane.ConclusionsThe main risk factor of death during CM was thus elevated plasma levels of IL-8 at inclusion. Follow-up of patients until D30 revealed marker profiles of disease aggravation and resolution for markers implicated in neutrophil activation, endothelium activation and damage, inflammatory and oxidative response. These results provide important insight into our understanding of CM pathogenesis and clinical outcome and may have important therapeutic implications.Graphical

Kinetics of viral DNA in body fluids and antibody response in patients with acute Monkeypox virus infection

We report the follow-up laboratory investigation of three MPXV cases infected in May-June 2022 from diagnosis to disease resolution, monitoring viral shedding in different body fluids and antibody kinetics. Out of 138 non-lesion samples, viral DNA was found in 92.3% saliva, 85.7% semen, 86.2% oropharyngeal swabs, 51.7% plasma, 46.1% stool, and 9.5% urine samples. Viral load quantified by digital PCR widely varied, but tend to be higher in oropharyngeal swabs, saliva, and stool. Replication competent virus was recovered from four out of seventeen samples, including 1 saliva, 1 oropharyngeal swabs, 1 semen, and 1 stool. The analysis of the antibody kinetics revealed that IgM, IgA, and IgG antibodies were detected within two weeks post-symptoms onset for all three patients, with IgG detected early on at day 4-8 and IgM and IgA showing lower titers along the time frame of the study. Antibody levels increased during the second week of illness with IgG reaching high titers.

P553 Active tuberculosis and opportunistic infections: Pooled safety analysis of ustekinumab through up to 5 years across all approved indications

Abstract Background Ustekinumab (UST) is an approved treatment for adults with inflammatory bowel disease (IBD: Crohn’s disease [CD] and ulcerative colitis [UC]), psoriasis (PsO), and psoriatic arthritis (PsA). Here, we present pooled safety analyses in these approved indications of patients (pts) with active tuberculosis (TB) and opportunistic infections (OIs) through 5 years (yrs) of UST treatment. Methods Pooled data included 13 Phase 2/3 UST studies through 5 yrs of CD and PsO, 2 yrs of UC, and 1 yr of PsA. OIs were identified by clinician review. Herpes zoster (HZ) was evaluated separately. Event rates per 100 pt yrs (PYs) are presented. Concomitant immunomodulators/corticosteroids were permitted in IBD and PsA pts. All pts who received ≥1 UST dose were included. In IBD, placebo (PBO) pts included data up to the first UST dose for pts initially treated with PBO, or &amp;gt;16 weeks after the last UST dose for UST pts who switched to PBO. Results Across all approved indications, 19 OIs including TB were reported, with rates in PBO of 0.40 and UST of 0.10 through 5 yrs in 13807 PYs of follow-up (Table 1); rates of HZ were 1.21 and 0.63, respectively. Of 19 OIs, 18 were in IBD pts and 1 in a PsO pt. Overall, 14/16 pts (12/13 UST) with OIs excluding TB were also receiving confounding concomitant medications. A total of 3 active TB cases (2 pts with CD and 1 pt with UC) were reported in PBO (n=2; 1 in a Hungarian CD pt 10 months after receiving last UST dose) and UST (n=1) pts (Table 1). One active TB case was reported in an asymptomatic South African CD pt treated with UST who had a positive QuantiFERON®-TB Gold test on routine screening and bronchial brushings positive for M. tuberculosis. Both CD pts completed TB treatment with disease resolution. The most common OIs were esophageal candidiasis (UST n=3; PBO n=2) and cytomegalovirus colitis (UST n=3; PBO n=1). Conclusion Rates of OIs, including active TB, in UST-treated pts were low across approved indications through up to 5 yrs with 13807 PYs of follow-up and not higher in UST pts vs PBO pts, suggesting no increased risk of OI with long-term UST treatment.

P749 Crohn’s disease stricture response and resolution with adalimumab therapy demonstrated with intestinal ultrasound. The STRIDENT randomised trial

Abstract Background Transmural healing is a treatment goal in the management of Crohn’s disease, and intestinal ultrasound (IUS) is potentially a sensitive, non-invasive and reproducible means to assess the response to treatment. Methods The STRIDENT (Stricture Definition and Treatment) study was a randomised controlled trial of standard dose monotherapy adalimumab versus intensive high-dose adalimumab combined with a thiopurine. Crohn’s disease patients with symptomatic intestinal strictures were randomised 2:1 to high dose adalimumab induction (160mg weekly for 4 weeks) with 40mg fortnightly maintenance plus thiopurine, with possible dose escalation at 4 and 8 months, versus standard dose adalimumab monotherapy. The primary endpoint was clinical response, defined as a reduction in the Obstructive Symptom Score (OSS) of ≥1, at 12 months. IUS was performed at baseline, 4, 8 and 12 months. IUS endpoints included stricture resolution (normalisation of pre-stenotic dilation (&amp;lt;2.5cm); reduced stricture bowel wall thickness (BWT ≥25% reduction); reduced colour doppler blood flow (inflammation, Limberg score ≤1) and normalisation of BWT (≤3mm). Patients with good quality baseline IUS and IUS-visible strictures were included for analysis. Results 77 patients underwent therapy randomisation. Of 63 patients with IUS-visible strictures 43 (68%) were in the intensive arm. Primary outcome was achieved by 32 (74%) patients in the intensive and 14 (70%) in the standard arms. Stricture resolution was seen in 1/5 non-responders and 18/45 responders. Median BWT reduced from 6.4mm (IQR 5.2-7.3mm) at baseline to 4.9mm (IQR 3-6mm) at 12 months (P&amp;lt;0.001). Clinical responders had significant reduction in median BWT from 6.0mm (IQR 4.5-7.1) at baseline to 4.3mm (IQR 3-5.7) at 12 months (P&amp;lt;0.001). There was no significant reduction in BWT at 4, 8 or 12 months in non-responders (P=0.26, P=0.29, P=0.26 respectively). BWT &amp;gt;3mm at 12 months occurred more often in non-responders than responders (P&amp;lt;0.05). Stricture resolution was seen in 13/36 in the intensive arm and 6/14 standard arm (P=0.75). The intensive arm had significant reduction in median BWT from 6.6mm (IQR 5.5-7.4mm) at baseline to 5.1mm (IQR 3-6.4mm) at 12 months (P&amp;lt;0.001). There was no significant reduction in BWT at 4, 8 or 12 months in the standard arm (P=0.75, P=0.42, P=0.09 respectively). There was no significant difference in BWT&amp;gt;3mm between trial arms at 12 months (P=1). Conclusion Stricture resolution and bowel wall thickness normalisation were demonstrated on intestinal ultrasound in stricturing Crohn’s disease patients treated with adalimumab therapy. Adalimumab therapy is associated with clinical improvement, and transmural improvement and healing, in patients with Crohn’s disease strictures.