Relapsing Course Research Articles

"Psychiatric oblivion": considerations on the hypothesis of a law.

The introduction of a law on psychiatric oblivion, similar to the recent one for oncological oblivion, presents numerous complexities due to the differences between the two areas of illness, especially in terms of recovery and clinical stability. While a definitive cure is often achievable in oncological diseases, in severe mental disorders, such as schizophrenia or bipolar disorder, complete remission in the absence of therapies is rare. Even in cases of effective treatment response, patients may exhibit subclinical symptoms or cognitive and functional deficits, making the concept of psychiatric oblivion particularly problematic. Some diagnostic categories, such as brief psychotic disorder or postpartum depression, could theoretically benefit from oblivion legislation, given the potentially limited course and frequent absence of relapses. However, for the majority of psychiatric conditions the requirement of a long period of remission without therapy appears difficult to achieve. An alternative could be the introduction of criteria based on the stabilization of maintenance therapy, but this would require a more complex and less easily standardized clinical judgment. Other limitations are the residual vulnerability to relapses, the difficulty in determining a precise medical history and the influence of persistent social stigmatization, which could undermine the effects of oblivion. Therefore, the creation of a law on psychiatric oblivion would require a restrictive and selective approach, focused on specific diagnoses and long-term clinical remission criteria, tailored to the clinical and adaptive peculiarities of mental illness.

Effectiveness of Tralokinumab in Different Phenotypes of Atopic Dermatitis: A Real-World Study.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritus and a relapsing course, affecting approximately 25% of children and 4-7% of adults. This study evaluated the efficacy, safety, and quality-of-life impact of tralokinumab, a humanized monoclonal antibody targeting interleukin-13 (IL-13), in treating moderate-to-severe AD in a real-world setting, with a focus on different AD phenotypes. An observational cohort of 30 adults treated with tralokinumab for ≥ 16weeks was analyzed. Clinical and demographic data were collected, and outcomes were assessed using the Eczema Area and Severity Index (EASI), Dermatology Life Quality Index (DLQI), and numeric rating scales (NRS) for pruritus and sleep disturbances. By week16, 60% achieved a 75% improvement inEASI (EASI75)and 31% reached a 90% improvement inEASI (EASI90), reflecting substantial clinical improvements. A ≥ 4-point reduction in pruritus NRS was observed in 63% of patients by week16, increasing to 70% by week32. Similarly, 75% achieved significant improvements in sleep disturbance NRS by week16, with sustained effects through week32. Subgroup analysis revealed superior clinical responses in patients with early-onset AD and atopic comorbidities. Lower total immunoglobulinE (IgE) levels at week16 correlated with better outcomes, suggesting total IgE as a potential biomarker. By week32, 70% of patients had a DLQI ≤ 5, indicating minimal quality-of-life impact. Additionally, 88% reached at least one therapeutic target, and 81% met composite endpoints combining clinician-assessed and patient-reported outcomes. The safety profile was consistent with clinical trials, with mild conjunctivitis and injection site reactions as the most common adverse events. These findings support tralokinumab as an effective and well-tolerated treatment, emphasizing the importance of phenotype-specific approaches in AD management.

Efficacy of low-dose rituximab versus immunosuppressants in refractory orbital inflammatory pseudotumors with intracranial extension

ObjectiveThe aim of this study was to compare the efficacy of low-dose rituximab (RTX) and immunosuppressants in treating orbital inflammatory pseudotumor (OIP) with intracranial extension, a refractory and high-relapse disease.MethodsPatients who had been diagnosed with refractory OIP with intracranial extension and who were refractory to systemic corticosteroids were retrospectively recruited at the Neuro-Ophthalmology Department at the Chinese People’s Liberation Army General Hospital between December 2018 and September 2022. After methylprednisolone pulse therapy, we added 2 mg of tacrolimus per day, 1500 mg of mycophenolate mofetil per day, or 200 mg of rituximab at days 1 and 15, and then monitored those with CD19+ B cells of under 1% as adjuvant therapy.ResultsEleven patients (six males and five females) were included, with a mean age of 45.5 ± 11.8 years (age range: 21–64 years). The average follow-up period was 3.8 years (range: 2–5). Eight patients (72.7%) had different levels of decreased vision at onset of the illness and four patients (36.4%) had severely impaired vision (three with no light perception, one with some light perception). Four patients (36.4%) showed clinical course worsening or lack of remission when treated with corticosteroids. Seven patients (63.6%) had a typical relapsing course, and the annual recurrence rate was higher than 7.36 ± 3.73 times. Of these seven, four (57.1%, 4/7) were able to undergo successful management with immunosuppressants. Three (42.9%, 3/7) failed with immunosuppressants but succeeded in controlling relapse with RTX.ConclusionOIP with intracranial extension is uncommon. More than half of patients with OIP with intracranial extension may be satisfactorily treated with corticosteroids combined with immunosuppressants. However, for patients who still experience recurrence or slow reduction of lesions after applying this combined therapy, RTX may be a better option.

Challenges in the Diagnosis and Management of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD).

Myelin oligodendrocyte glycoprotein antibody-associated disease has been recently identified to be a distinct autoimmune central nervous system disorder. There is significant clinical and radiological overlap with multiple sclerosis and aquaporin-4-IgG-associated neuromyelitis optica spectrum disorders. Clinical course is variable in that patients may have a monophasic or relapsing course, disease severity is unpredictable, and unlike other idiopathic autoimmune inflammatory disorders, there is no gender predilection and it is more likely to affect pediatric population. There are no clear-cut treatment guidelines. Duration and dose of oral steroids after the first attack, role of immunosuppressants in relapsing disease, and duration of therapy for the latter are not certain. Currently, there are no disease-specific therapies available, though some novel therapies are under trial. Some of these challenges will be addressed in this paper.

P0806 Monitoring of vedolizumab therapy using fecal calprotectin, abdominal ultrasound, and drug levels in ulcerative colitis: a predictive algorithm

Abstract Background Ulcerative colitis (UC) is a chronic inflammatory bowel disease with a relapsing course. Vedolizumab, an anti-integrin, induces clinical remission in UC, but response is typically evaluated after 14 weeks. Earlier predictive markers could optimize treatment. This study aimed to develop an algorithm using baseline and week 6 data (especially abdominal ultrasound, fecal calprotectin, and drug levels) to predict clinical response and remission at week 14. Methods In this prospective study, 37 UC patients were recruited from 2018 to 2024, and 17 were included in the final analysis. The primary endpoint was clinical response or remission at week 14, based on significant changes from baseline to week 6 in at least two markers (vedolizumab ≥ 24 µg/ml, ≥ 25% reduction in colon wall thickness, or ≥ 50% reduction in fecal calprotectin). Secondary endpoints included outcomes at week 22. Statistical methods included among others Mann-Whitney U-tests, Fisher’s exact tests, and logistic regression. Results Vedolizumab levels at week 6 were the most reliable individual marker for predicting clinical response at week 14, with 0.67 sensitivity and 0.62 specificity. In addition, leukocytes and pancreatic elastase were negatively associated with clinical response, while zonulin showed a positive association (p < 0.001). For clinical remission, colon wall thickness reduction and the combined predictive marker demonstrated perfect sensitivity (1.00) and negative predictive value (1.00). A significant association was found between reduced colon wall thickness and clinical remission (OR = 13.91, 95% CI: 1.13–1986.85). Conclusion Early changes in vedolizumab levels, fecal calprotectin, and colon wall thickness can predict clinical response and remission in UC. Colon wall thickness proved the strongest predictor of remission. Larger studies are needed to validate and refine this algorithm for personalized vedolizumab therapy.

P0520 Association between interoception and Visceral Hypervigilance in patients with Inflammatory Bowel Disease

Abstract Background Due to the relapsing course of inflammatory bowel diseases (IBD) with varying disease activity and symptom burden, patients tend to monitor symptoms and bodily sensations to recognize early signs of relapses. Interoception is the ability to perceive and evaluate internal processes of the body. Visceral hypervigilance (VH) describes anxiety and increased attention towards gastrointestinal symptoms. It has been shown to be associated with psychologic comorbidities and reduced quality of life in patients with IBD1, but the factors causing VH are still unknown. In this study we explored whether changes in interoceptive abilities (accuracy, I-acc; sensibility, I-sens and awareness, I-aw) are associated with VH. Methods Adults with IBD (n=34) performed a heartbeat tracking task (Schandry, 1981) for assessment of I-acc and completed questionnaires to assess VH (Visceral Sensitivity Index, VSI) and I-sens. Correlations between I-acc and I-sens were used for an approximation of I-aw. Associations were examined using t-tests and Pearson correlation. Results A preliminary examination of the current sample (recruitment is ongoing) showed no significant association between VH and I-acc (r=-0.041; p=0.817) or I-sens (r=0.236; p=0.178). Comparison of a low VH (VSI<20) vs high VH (VSI>40) group showed no significant differences in I-acc or I-sens (VSI<20: n=11; VSI>40: n=9; I-sens: t= -1,183; p= 0,126; I-acc: t= 0,47; p=0,322). Moreover I-aw was not significantly different between a high VH and a low VH group (z=0.218, p=0.828). I-acc and I-sens correlated positively (r=0.374 p = 0.018). VH was strongly correlated with symptoms of anxiety (r=0.659, p<0.001) and depression (r=0.618; p<0.001), but I-acc was not significantly associated with symptoms of anxiety and depression (anxiety r=0.188 p=0.328; depression r=0.067, p=0.729). I-sens was associated with symptoms of anxiety (r= 0.371, p = 0.048), but not with symptoms of depression (r=0.32, p=0.091). Conclusion Our preliminary results suggest no associations between VH and objective or subjective interoceptive abilities in patients with IBD. This may be owed to the small sample size with only few patients showing high or low VH. Moreover - even though previous data showed a relationship between perception of cardiac and gastrointestinal signals, and both communicate via the vagal nerve 2-3 - heart-beat tracking may not be the optimal task to measure interoception in patients with IBD. VH and interoception should be examined in larger IBD samples that include individuals with a higher symptom burden. Future studies may also explore further possibilities to assess interoception in IBD patients.

MOG-IgG is rare in AQP4-IgG seronegative NMO phenotype in Brazil.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease most frequently characterized by a neuromyelitis optica (NMO) phenotype, comprising both simultaneous or sequential optic neuritis (ON) and longitudinally extensive transverse myelitis (LETM). Symptoms of brainstem, diencephalic and cerebral involvement may also occur. While most NMOSD patients test positive for serum aquaporin-4 (AQP4) antibodies, some seronegative patients test positive for oligodendrocyte glycoprotein-IgG (MOG-IgG). Early identification of seropositive MOG-IgG seropositive patients among those with AQP4-IgG seronegative NMO phenotype may impact disease treatment and outcome. To determine the frequency of MOG-IgG in patients with AQP4-IgG seronegative NMO phenotype at a single reference center in Brazil and to analyze factors influencing their identification. A retrospective review of medical records of patients who presented with NMO phenotype and met the 2015 IPND criteria for NMOSD without AQP4 antibodies was conducted in a single center in Brazil. Patients were tested for serum AQP4 antibodies and retrospectively for MOG-IgG using cell-based assays. In addition to demographic, clinical, and imaging data, information on time intervals between disease onset and MOG-IgG testing, as well as the most recent relapse to MOG-IgG testing, was collected. Out of 118 patients tested for MOG-IgG, 28 (23.7 %) presented with NMO phenotype and met the 2015 IPND criteria for NMOSD without AQP4-IgG. Three (10.7 %) of them tested positive for MOG-IgG serostatus. All were females and had a median age of 26 (11-34) years at disease presentation. The median disease duration was 11.2 yrs. Two patients had a relapsing course. Optic neuritis, myelitis, and brainstem syndrome were the most common presenting symptoms. The median annualized relapse rate was 0.25, and the median EDSS score at the most recent visit was 2.0 (1.5-5.0). There were 25 double seronegative patients, 21 (84 %) of whom were female and non-Caucasian; the median age at disease onset was 30 years (2-60), and the median EDSS at most recent visit was 4.0 (0 - 8.0). The study identified MOG-IgG antibodies in 10.7 % of a cohort with AQP4-IgG seronegative NMO phenotype. Immunosuppressive treatment and long intervals between disease attacks and antibody testing may have impacted the frequency of MOG-IgG seropositivity. As MOG-IgG testing is crucial for diagnosing MOGAD in AQP4-IgG seronegative NMO phenotype, we highlight the need for broader and timely testing to improve diagnostic accuracy in resource-limited settings.

Features of the Clinical Course of Odontogenic Inflammatory Diseases of the Jaws and Soft Tissues in Drug Users

The objective: to analyze the features of the clinical course of odontogenic inflammatory diseases of the jaws and paramaxillary soft tissues in drug addicts. Materials and methods. 294 drug-addicted patients with odontogenic inflammatory diseases of the jaws and soft tissues were examined and treated. All patients underwent a generally accepted clinical and X-ray examinations at the first visit and during the course of treatment. Primary odontogenic inflammatory processes in the jaw were found in the patients, namely: periodontitis, periostitis and osteomyelitis. The reliability of the examination results was calculated according to Student’s criteria. Differences were considered significant at p < 0.05. Results. Atypical clinical and radiological features of the course of periodontitis, periostitis, osteomyelitis, abscesses and phlegmons were found in the study participants, namely: progressive nature, significant prevalence of lesions, peculiar clinical symptoms. Unsatisfactory healing of post-extraction and postoperative wounds, very low effectiveness of the medical measures, relapse course, which should be taken into account during the treatment of this category of patients, were found in drug addicts. Conclusions. The developed schemes for the treatment of odontogenic purulent-inflammatory diseases of the soft tissues of the maxillofacial region and neck in drug-addicted persons contribute to the faster elimination of the purulent-inflammatory process (compared to traditional treatment), improve the healing of postoperative purulent wounds, and reduce the occurrence of local postoperative inflammatory complications in 3–4 times.

Chronic inflammatory demyelinating polyradiculopathy as a paraneoplastic manifestation of metastatic melanoma

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disease that leads to proximal greater than distal weakness. It follows a relapsing course and requires treatment with chronic immune suppressing therapy such as steroids or intravenous immunoglobulin infusions. The vast majority of cases are idiopathic. However, there has been an established association with malignancy. Hematologic malignancies are the most commonly associated, but solid tumors are implicated as well. CIDP associated with melanoma has been reported in several previous case reports. Despite these reports, this association is not widely known. We report a case of a patient with a remote history of resected melanoma who developed severe refractory CIDP. He was found to have a recurrent metastatic melanoma. He experienced sustained clinical improvement with treatment of both the CIDP and malignancy. We then compare the characteristics of this case with others reported in the literature. This case along with other reports highlights the importance of being aware of this association and emphasizes that treatment of both the neuropathy and malignancy leads to maximal clinical effect.

Predictors of a relapsing course in myelin oligodendrocyte glycoprotein antibody-associated disease

BackgroundMyelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently described demyelinating disorder, and children represent about 50% of all cases. Almost half of the patients experience relapses, but very few...

Darier disease: Current insights and challenges in pathogenesis and management.

Darier disease is a rare autosomal dominant genodermatosis caused by mutations in the ATP2A2 gene encoding for sarcoendoplasmic reticulum Ca2+ ATPase isoform 2. The skin disease is characterized by a chronic relapsing course with recurrent reddish-brown keratotic papules and plaques located mainly in seborrhoeic areas. Due to chronic inflammation and epidermal barrier defects of the skin, patients often develop severe bacterial and viral superinfections. Therapeutic options are limited, mainly symptomatic and in most cases unsatisfactory in the long term. Patients are advised to avoid aggravating factors such as high temperature, high humidity, UV radiation and mechanical irritation. To prevent superinfection, antiseptics and periodic use of topical corticosteroids are fundamental in treatment. In case of bacterial and viral superinfection, systemic anti-infective therapy is often necessary. Currently, the most effective treatment option for extensive and persistent skin lesions is systemic retinoids, which are thought to mainly target the epidermal compartment (e.g. by reducing hyperkeratosis). One hallmark of Darier disease patients is chronic skin inflammation. We and others have previously reported Th17 cells in the dermal infiltrate of inflamed Darier disease skin. Counteracting inflammation by blocking the IL-23/IL-17 axis improved skin manifestations in a small cohort of previously therapy-resistant patients over 1 year. Furthermore, several other topical treatment options for mild disease as well as various ablative therapies and surgical excision have been proposed to be effective in some patients with hypertrophic skin lesions. This article aims to outline the pathogenesis, clinical features, diagnosis/differential diagnosis and available treatment modalities of Darier disease.

Diagnostic significance of the method of computerized joint vibration analysis in studying the functional state of temporomandibular joints

polyetiology, progressive course and high frequency of relapses is one of the urgent problems of modern dentistry. Different conceptual approaches to the analysis of etiological and pathogenetic aspects of the development of dysfunctional TMJ disorders predetermine the increased interest in the search for highly informative diagnostic methods, especially at the stage of preclinical manifestations.Goal. Evaluation of possibilities of computerized joint vibration analysis method in diagnostics of TMJ functional state.Materials and methods. The study involved 42 people of both sexes with physiologic types of bite, preserved tooth rows, no signs of functional disorders in TMJ and masticatory muscles. The patients underwent clinical dental examination, «Hamburg test», selective grinding of teeth, and measurement of mouth opening amplitude. Joint vibration analysis was performed on the hardware-software complex «BioPAK» with registration of TMJ noise oscillations according to the following indices: «Total Integral», «High Integral», «Low Integral», «Ratio». A flow chart (Ishigaki S. et al., 1993) was used to interpret the numerical values. The functional state of TMJ was de-termined according to the flowchart using numerical parameters in accordance with the classification of TMJ disorders (Wilkes С.Н., 1989).Results. In patients with physiologic occlusion, according to joint vibration analysis, Me «Total Integral» of the right TMJ was 11.7 PaHz, left TMJ – 12.6 PaHz, [Q-25; Q-75] – [9.3; 15.1] PaHz and [10.5; 18.3] PaHz respectively, Me «High Integral» of the right TMJ – 1.3 PaHz, left TMJ – 1.4 PaHz, [Q-25; Q-75] – [1.0; 1.8] PaHz and [1.2; 2.1] PaHz respectively, with no statistically significant (p≤0.05) differences in the studied parameters between the right and left TMJ.Conclusions. The diagnosis of «structurally intact» TMJ, corresponding to stage I of the American classification of TMJ disorders (Wilkes S.N., 1989) in people with physiologic types of bite, is confirmed by the numerical values [Q-25; Q-75] of «Total Integral», «High Integral» (block diagram of S. Ishigaki et al., 1993), the degree of maximum mouth opening [43; 50] mm in the absence of pronounced signs of facial asymmetry.

Clinical characteristics of pediatric and adult myelin oligodendrocyte antibody-associated disease (MOGAD): A single-center study in the Northeast

BackgroundMyelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an immune-mediated, inflammatory, demyelinating disorder with a range of clinical presentations including acute disseminated encephalomyelitis (ADEM), optic neuritis (ON), myelitis, and cerebral cortical encephalitis. Phenotypic expression of MOGAD varies with age. MOG antibody (MOG-Ab) titers at disease onset, as well as longitudinally, may predict clinical disease course. The objectives of this study were to (1) describe a cohort of pediatric and adult patients with MOGAD at a single center and (2) investigate if clinical outcomes correlate with ethnicity and MOG-Ab. MethodsThe clinical data of 36 pediatric and adult patients with MOGAD who were evaluated at onset and longitudinally were collected between January 2018 and June 2023 at our center. Inclusion criteria were positive MOG-Ab titers, a presentation consistent with proposed consensus criteria for MOGAD, and at least one initial or follow-up visit at our center. Patients were divided into monophasic and relapsing courses. Demographic data and clinical phenotypes were assessed as possible predictors of relapsing disease. ResultsWe describe demographic and clinical characteristics of 36 patients with MOGAD. Hispanic adults and children had increased rates of disease relapse compared to other ethnicities. Male sex and pediatric onset disease were also associated with increased risk of relapse. MOG-Ab titers at disease onset were not associated with a particular disease course. In adults, an initial phenotype of unilateral optic neuritis was associated with monophasic disease. ConclusionOur findings within a diverse population suggest that specific characteristics, both of patients and of disease presentation, may be associated with a monophasic or relapsing course. Additional studies with larger cohorts are needed.

Deprescribing Antidepressants in Children and Adolescents: A Systematic Review of Discontinuation Approaches, Cross-Titration, and Withdrawal Symptoms.

Background: Antidepressant medications, including selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), are commonly used to treat depressive, anxiety, and obsessive-compulsive disorders in youth. Yet, data on discontinuing these medications, withdrawal symptoms, and strategies to switch between them are limited. Methods: We searched PubMed and ClinicalTrials.gov through June 1, 2024, to identify randomized controlled trials assessing antidepressant discontinuation in youth. We summarized pediatric pharmacokinetic data to inform tapering and cross-titration strategies for antidepressants and synthesized these data with reports of antidepressant withdrawal. Results: Our search identified 528 published articles, of which 28 were included. In addition, 19 records were obtained through other methods, with 14 included. The corpus of records included 13 randomized, double-blind, placebo-controlled trials (3026 patients), including SSRIs (K = 10), SNRIs (K = 4), andTCAs (K = 1), ranging from 4 to 35 weeks. Deprescribing antidepressants requires considering clinical status, treatment response, and, in cross-titration cases, the pharmacokinetics and pharmacodynamics of both medications. Antidepressant withdrawal symptoms are related to the pharmacokinetics of the medication, which vary across antidepressants and may include irritability, palpitations, anxiety, nausea, sweating, headaches, insomnia, paresthesia, and dizziness. These symptoms putatively involve changes in serotonin transporter expression and receptor sensitivity, impacting the serotonin, dopamine, and norepinephrine pathways. Conclusions: Although approaches to deprescribing antidepressants in pediatric patients are frequently empirically guided, accumulating data related to the course of relapse and withdrawal symptoms, as well as the pharmacokinetic and pharmacodynamic properties of medications, should inform these approaches. Recommendations within this review support data-informed discussions of deprescribing-including when and how-that are critically important in the clinician-family-patient relationship.

Blood neutrophils, oligoclonal bands and bridging corticosteroids as predictive factors for MOGAD course: Insights from a multicentric Portuguese cohort

BackgroundMyelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a heterogeneous entity with either a monophasic or relapsing course. Well-established predictors of relapsing disease are lacking. ObjectiveIdentifying predictors of relapsing MOGAD, particularly at disease onset. MethodsA multicentre observational retrospective study was conducted to characterise a cohort of Portuguese adult MOGAD patients. Patients were identified from participating centre databases. Clinical and demographic data were collected from medical records. Bivariate analysis was conducted to compare patients with relapsing and monophasic MOGAD. Significant variables were included in a stepwise multiple regression analysis to identify independent predictors of relapse. ResultsEighty-seven MOGAD patients from 8 public hospitals were included. Relapsing MOGAD was found in 35.6% (n = 31). Mean diagnostic delay was 3.2 (±6.2) years and time to relapse was 4.4 (±6.4) years. Multiple logistic regression showed that higher neutrophil count (p < 0.01), presence of oligoclonal bands (p = 0.025) and no bridging corticosteroids (p = 0.038) at first attack were predictive of relapsing MOGAD. ConclusionNeutrophil count and oligoclonal bands at first attack may facilitate early decision-making regarding maintenance immunotherapy. Bridging corticosteroids may also influence the course of MOGAD. Further studies with prospective design are warranted.

Protective effects and mechanisms of HuDiChangRong capsule on TNBS-induced ulcerative colitis in mice

Ethnopharmacological relevanceUC, characterized by chronic inflammation primarily affecting the colon and rectum, follows a protracted relapsing course marked by inflammation and an abundance of free radicals at the onset. Hudichangrong Capsule (HDCRC), a traditional Chinese medicinal formula, has long been employed in the treatment of UC and chronic bacillary dysentery, exhibiting positive therapeutic outcomes and a high rate of cure in clinical practice. Aim of the studyThe precise mechanism underlying its efficacy for UC remains elusive. Our objective was to investigate the anti-inflammatory effect and underlying mechanisms of HDCRC on TNBS-induced UC. Materials and methodsHere, we introduced HDCRC and induced UC using TNBS. SPF BALB/c mice were divided into 6 groups as follows: control group, colitis model group, colitis treated with sulfasalazine (400 mg/kg) group, and colitis treated with HDCRC (156, 312, and 624 mg/kg) groups. To assess the effects of HDCRC on colitis, we measured body weight loss, disease activity index (DAI), colon length, tissue damage, degree of inflammation, immune capacity, and oxidative stress. Additionally, we evaluated the TLR-4/MyD88 pathway and its downstream signaling using immunohistochemistry, real-time qPCR, and Western blot. Network pharmacology was used for main target prediction. 16s rRNA was employed for gut microbiota detechtion and UPLC-QTOF-MS was used for its and its metabonomics. ResultsHDCRC significantly slowed weight loss, ameliorated DAI, restored colon length, alleviated TNBS-induced tissue damage. It exerted the therapeutic effects via reducing oxidative stress, restoring immune balance, normalizing the inflammatory mediator levels and restoring intestinal barrier integrity. Furthermore, HDCRC mainly alleviate UC via suppressing the TLR-4/MyD88 pathway and its downstream signaling. The key components of the downstream pathway, including TLR-4, MyD88, NF-κB p65, ERK, p-JNK, p38, p-JAK1, JAK1, p-STAT3, and STAT3, were improved, thereby ameliorating the TNBS-induced injury. In addition, HDCRC could regulate gut microbiota (eg. Erysipelaloclostridium,etc.) and its metabonomics (eg. Vitamin B6 metabolism) in UC mice. ConclusionsIn conclusion, HDCRC exerts a protective effect against TNBS-induced UC in mice by inhibiting the TLR-4/MyD88 pathway and its downstream signaling, and partially JAK1/STAT3, suppressing oxidative stress, regulating immunity, restoring intestinal barrier integrity, and regulating gut microbiota and its metabonomics.

Identification, risk factors, and clinical course of CNS relapse in DLBCL patients across 19 prospective phase 2 and 3 trials-a LYSA and GLA/ DSHNHL collaboration.

Progression or relapse in the central nervous system (CNS) remains a rare but mostly fatal event for patients with diffuse large B-cell lymphoma (DLBCL). In a retrospective analysis of 5189 patients treated within 19 prospective German and French phase 2/3 trials, we identified 159 patients experiencing a CNS event (relapse: 62%, progression: 38%). Intracerebral, meningeal, intraspinal, or combined involvement was reported in 44%, 31%, 3%, and 22% of patients, respectively. 62 of 155 evaluable patients (40%) showed concurrent systemic progression/ relapse. 82% of all CNS events occurred within two years after study inclusion or randomization. 87% of patients showed extranodal involvement outside the CNS. Patients generally had poor outcomes with a median overall survival (OS) of 3.4 months (95% CI 2.9-4.2) and a 2-year OS of 15% (10-22%). Outcomes did not differ depending on the site or time point of CNS events. Patients with isolated CNS events demonstrated significantly better OS (p = 0.023). Twenty-five patients were consolidated with autologous or allogeneic stem cell transplantation and achieved a 3-year OS of 36% (20-66%). This large study including more than 5000 DLBCL patients highlights the unmet medical need to improve the outcome of DLBCL patients suffering from CNS relapse.

Treatment of Refractory Mucosal Leishmaniasis Is Associated with Parasite Overexpression of HSP70 and ATPase and Reduced Host Hydrogen Peroxide Production (Brief Report).

Mucosal leishmaniasis (ML) is a deforming type of American Tegumentary Leishmaniasis caused by Leishmania (Viannia) braziliensis that frequently does not respond to treatment. Despite its relapsing clinical course, few parasites are usually found in mucosal lesions. Host and parasite factors may be responsible for this paradox in the pathogenesis of the disease, allowing for both a low parasite burden and the inability of the host to clear and eliminate the disease. In this work, we present a clinical case of relapsing ML that was treated for 25 years without success with SbV, N-methyl glucamine, sodium stibogluconate, amphotericin B deoxycholate, gabromycin, antimonial plus thalidomide, liposomal amphotericin B, Leishvacin (a vaccine made in Brazil) and miltefosine. In a comparative analysis using nanoscale liquid chromatography coupled with tandem mass spectrometry of protein extracts of L. (V.) braziliensis promastigotes isolated from the patient and from the reference strain (MHOM/BR/94/M15176), we observed increases in ATPase and HSP70 protein levels in the parasite. We also observed an impairment in the production of hydrogen peroxide by peripheral mononuclear blood monocytes (PBMCs), as assessed by the horseradish peroxidase-dependent oxidation of phenol red. We hypothesise that these parasite molecules may be linked to the impairment of host parasiticidal responses, resulting in Leishmania persistence in ML patients.

MSCT enterography score for prediction of disease severity in patients with active ulcerative colitis

BackgroundUlcerative colitis (UC) is a chronic non-specific inflammatory bowel disease (IBD). It is characterized by diffuse inflammatory process of the bowel mucosa with a relapsing course. The precise evaluation of UC severity is pivotal in the therapeutic decision-making. Modified Mayo score is consistently used for the evaluation of the disease activity which depends on the patient’s symptoms as well as the colonoscopic findings. The aim of this study is to assess the role of the CT enterography (CTE) scoring system in the evaluation of the disease severity in ulcerative colitis. From October 2022 to July 2023, 66 patients with known ulcerative colitis patients at time of disease activity were referred from the inflammatory bowel disease unit for radiological assessment by CTE. CT images were analyzed to determine the anatomical location of the affected bowel segments, mucosal thickening and hyperenhancement as well as the extra-enteric involvement. Correlation with the modified Mayo score was established.ResultsOur results showed a statistical significant correlation between modified Mayo score and CTE with a P value of 0.000. The correlation coefficient is r = 0.964. The cut-off value of the optimal CTE score to predict mild and moderate UC was 7.5 with 0.996 area under the ROC curve, 92%sensitivity and 100% specificity. The cut-off value of the optimal CTE score to predict moderate and severe UC was 10.5 with 0.983 area under the ROC curve, 90.6% sensitivity and 100% specificity.ConclusionsCTE is a reliable diagnostic method in the systematic assessment of the disease severity of active ulcerative colitis. CTE score shows a strong proportionate correlation with modified Mayo score. The aggravation of the course of the disease increased the CTE score. CTE scoring system can help plan the therapeutic strategy and predict prognosis.

The affective temperaments as a prognostic factor in the course of alcohol addiction – a key to enhance diagnoses and therapy?

The paper outlines the role of affective temperaments, as defined by Akiskal, in the development and maintenance of alcohol use disorders with a particular focus on the clinical course of addiction. Among affective temperaments, a cyclothymic temperament seems to play a key role in the development and maintenance of alcohol use disorders, and have the greatest influence on the clinical course of addiction. A high cyclothymic score is associated with inter alia an earlier onset of drinking and alcohol dependence, a negative course of alcohol dependence, relapse and alcohol craving. The structure of affective temperaments is also a predictor of suicidal behavior and drug addiction in the alcohol addict population. Interest has been growing regarding the role of affective temperament in the development and course of alcohol dependence; however, further research in this area is needed. An understanding of the temperamental determinants of alcohol dependence in the affective dimension may significantly support diagnostic and therapeutic procedures. Affective temperament profile may be suggestive of alcohol use disorders and may be a primary prognostic factor of craving and relapse, potential suicide, treatment motivation and the co-occurrence of drug dependence among patients with alcohol use disorder.