Course Of Disease Research Articles

Regular use of fish oil supplements and course of cardiovascular diseases: prospective cohort study

ObjectiveTo examine the effects of fish oil supplements on the clinical course of cardiovascular disease, from a healthy state to atrial fibrillation, major adverse cardiovascular events, and subsequently death.DesignProspective cohort...

Predictors of Complicated Disease Course in Children andAdults With Ulcerative Colitis: A Nationwide Study From the epi-IIRN.

Data on predictors of complicated ulcerative colitis (UC) course from unselected populations cohorts are scarce. We aimed to utilize a nationwide cohort to explore predictors at diagnosis of disease course in children and adults with UC. Data of patients diagnosed with UC since 2005 were retrieved from the nationwide epi-IIRN cohort. Complicated disease course was defined as colectomy, steroid-dependency, or the need for biologic drugs. Hierarchical clustering categorized disease severity at diagnosis based on complete blood count, albumin, C-reactive protein and erythrocyte sedimentation rate (ESR), analyzed together. A total of 13 471 patients with UC (1427 [11%] pediatric-onset) including 103 212 person-years of follow-up were included. Complicated disease course was recorded in 2829 (21%) patients: 1052 (7.9%) escalated to biologics, 1357 (10%) experienced steroid-dependency, and 420 (3.1%) underwent colectomy. Probabilities of complicated disease course at 1 and 5 years from diagnosis were higher in pediatric-onset (11% and 32%, respectively) than adult-onset disease (4% and 16%; P < .001). In a Cox multivariate model, complicated course was predicted by induction therapy with steroids (hazard ratio [HR], 1.5; 95% CI, 1.2-2.0), extraintestinal manifestations (HR, 1.3; 95% CI, 1.03-1.5) and the disease severity clusters of blood tests (HR, 1.8; 95% CI, 1.01-3.1), while induction therapy with enemas (HR, 0.6; 95% CI, 0.5-0.7) and older age (HR, 0.99; 95% CI, 0.98-0.99) were associated with noncomplicated course. In this nationwide cohort, the probability of complicated disease course during the first 5 years from diagnosis was 32% in pediatric-onset and 16% in adults with UC and was associated with more severe clusters of routinely collected laboratory tests, younger age at diagnosis, extraintestinal manifestations, and type of induction therapy.

NEUROFILAMENTS AS A POTENTIAL BIOMARKER IN PATIENTS WITH MULTIPLE SCLEROSIS: A REVIEW OF LITERATURE

Background: Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease of the central nervous system (CNS) characterized by demyelination, axonal damage and loss of neurons. Its growing incidence has determined the need for more intensive research towards effective models for managing disease progression and evaluation of treatment response. Finding clinically relevant biomarkers has been a significant challenge. Purpose: This review aims to summarize the findings from current relevant literature sources on neurofilaments as a potential biomarker of diagnostic and prognostic value in patients with MS. Results: Recently, neurofilaments have been identified as the most promising and informative biomarkers of axonal damage and loss. Neurofilament concentration demonstrates a strong association with the disease course, activity and progression, disability accumulation and response to disease-modifying treatment. A significant correlation with future relapse rates, symptom worsening and risk of conversion from clinically isolated syndrome (CIS) to definite MS has also been established. Several MS therapies have demonstrated a substantial reduction in neurofilament levels upon treatment initiation. Conclusion: The results available from real-world studies and clinical trials regarding neurofilaments as a reliable predictor and indicator of MS disease course are encouraging. They have consistently proven to be of utility if integrated into the diagnostic and therapeutic algorithm of MS patients. This review encompasses undeniable data confirming the considerable potential of neurofilaments for becoming the first globally verified biomarker for MS. The accessibility, safety, low cost and possibility for serial evaluation make the neurofilaments the perfect component to be implemented in routine clinical tests for MS.

Hidradenitis suppurativa: definition, epidemiology, etiology, diagnosis (part 1)

Hidradenitis suppurativa (HS) is a chronic recurrent skin disease characterized by development of autoimmune inflammation in the infundibulum of the hair follicle and apocrine sweat glands located in the axillary, inguinal, anogenital regions, submammary folds, near the areola of mammary glands and the umbilical region. HS is difficult to treat and has an extremely negative impact on the quality of life. HS is separated into a distinct clinical entity fundamentally different in etiopathogenesis from acute bacterial hidradenitis. The exact prevalence of HS is unknown, it varies greatly in different studies ranging from 0.03 to 4% in general population. The detection of IL-1β, IL-23, and IL-17 in the lesions indicates the key role of autoimmune inflammation involving Th17-lymphocytes in the pathogenesis of HS. Risk factors include smoking, obesity, mechanical friction, genetic predisposition. The diagnosis of HS relies on three obligatory criteria: characteristic distribution, typical morphology of the lesions and relapsing, chronic disease course. There is no “gold standard” in assessing the severity of the disease, since all available scoring systems have many limitations, therefore many questions regarding this disease remain unsolved at present — from terminology and clear and most objective assessment criteria for the severity of the process to the development of native clinical guidelines.

Primary adrenal insufficiency developed 22 years after the diagnosis of light and heavy chain deposition disease: a case report.

Monoclonal immunoglobulin deposition diseases (MIDDs), including light and heavy chain deposition disease (LHCDD), are rare and heterogeneous disorders associated with underlying B-cell clonal disorders. Adrenal involvement is a potential extrarenal manifestation of MIDDs; however, limited data are available regarding its prevalence and clinical presentation. Herein, the present report describes, for the first time, a case of primary adrenal insufficiency that developed twenty-two years after a diagnosis of LHCDD had been made. A 69year-old woman with a 10year history of hemodialysis suddenly became bedridden after falling down stairs in the absence of focal neurological deficits. Subsequently, she experienced appetite loss, nausea, vomiting, a fever of unknown origin, and unexplained hypotension. Several months later, primary adrenal insufficiency and normal pressure hydrocephalus were diagnosed and successfully managed. The long-term clinical prognosis of MIDDs has not been fully elucidated despite recent advances in the management of the disorders. This report may contribute to improving our understanding of the disease course.

Hypopituitarism with secondary adrenocortical insufficiency and arginine vasopressin deficiency due to hypophysitis after COVID-19 vaccination: a case report

BackgroundAlthough vaccination against coronavirus disease (COVID-19) has several side effects, hypopituitarism due to hypophysitis has rarely been reported.Case presentationAn 83-year-old healthy woman, who had received her fourth COVID-19 vaccine dose 2 days before admission, presented to the emergency department with difficulty moving. On examination, impaired consciousness (Glasgow Coma Scale: 14) and fever were observed. Computed tomography and magnetic resonance imaging of the head revealed swelling from the sella turcica to the suprasellar region. Her morning serum cortisol level was low (4.4 μg/dL) and adrenocorticotropic hormone level was normal (21.6 pg/mL). Central hypothyroidism was also suspected (thyroid stimulating hormone, 0.46 μIU/mL; free triiodothyronine, 1.86 pg/mL; free thyroxine, 0.48 ng/dL). Secondary adrenocortical insufficiency, growth hormone deficiency, delayed gonadotropin response, and elevated prolactin levels were also observed. After administration of prednisolone and levothyroxine, her consciousness recovered. On the 7th day of admission, the patient developed polyuria, and arginine vasopressin deficiency was diagnosed using a hypertonic saline test. On the 15th day, the posterior pituitary gland showed a loss of high signal intensity and the polyuria resolved spontaneously. On the 134th day, the corticotropin-releasing hormone loading test showed a normal response; however, the thyrotropin-releasing hormone stimulation test showed a low response. The patient’s disease course was stable with continued thyroid and adrenal corticosteroid supplementation.ConclusionsHerein, we report a rare case of anterior hypopituitarism and arginine vasopressin deficiency secondary to hypophysitis following COVID-19 vaccination.

Challenges faced by older people with dementia during the COVID-19 pandemic as perceived by professionals: a qualitative study with interviews.

Previous studies have highlighted a decline in the mental health of older adults over the course of the coronavirus disease 2019 (COVID-19) pandemic. Few studies have determined the possible causes of behavioural and psychological symptoms of dementia during COVID-19 in a comprehensive manner. We aimed to identify the challenges faced by older adults with dementia during the COVID-19 pandemic. This study adopted a qualitative approach to understanding the perceptions of healthcare professionals, such as regarding the negative effects of COVID-19 on the mental health of people with dementia. Between January and March 2022, the authors conducted individual in-depth interviews on how COVID-19 affected the stress levels, care, and self-determination of people with dementia. Qualitative data from the individual interviews were data cleansed to ensure the clarity and readability of the transcripts. The qualitative data were then analyzed by inductive manual coding using a qualitative content analysis approach. The grouping process involved reading and comparing individual labels to cluster similar labels into categories and inductively formulate themes. Qualitative analysis extracted 61 different semantic units that were duplicated. Seven categories were inductively extracted using a grouping process. These were further integrated to extract the following four themes: fear of personal protective equipment (PPE), loneliness, dissatisfaction with behavioural restrictions and limitations of video calls, and family interference with service use. People with dementia often faced mental distress during the pandemic owing to preventive measures against COVID-19, and a lack of awareness and understanding of such preventive measures worsened their distress. They experienced a severe sense of social isolation and loneliness. Findings also indicated that families tended to ignore the needs of people with dementia and their decisions and opinions regarding healthcare service use.

Lipoprotein glomerulopathy with markedly increased arterial stiffness successfully treated with a combination of fenofibrate and losartan: a case report

BackgroundLipoprotein glomerulopathy (LPG) is a apolipoprotein E (ApoE)-related glomerular disease and has been associated with type III hyperlipidemia. Without appropriate treatment, chronic kidney disease (CKD) caused by LPG progresses, and approximately half of the patients develop end-stage kidney disease within 1–27 years of disease onset. However, few studies have highlighted the clinical course of cardiovascular diseases (CVDs) in patients with LPG. Herein, we report the first case of LPG in which the CVD risk was assessed using arterial stiffness.Case presentationA 32-year-old Japanese man was referred to our hospital due to persistent proteinuria. Kidney biopsy showed markedly dilated capillary lumens containing pale-stained thrombi, which stained positively with Oil Red O. Electron microscopy revealed the presence of thrombi in the capillary lumen with low electron density and vacuoles of various sizes in part of the thrombi. Toluidine blue and Sudan IV stains were used to stain the thin sections of Epon-embedded tissue samples for electron microscopy. Sudan IV-positive droplets were observed in the capillary lumens, vascular walls, and cytoplasm of tubular cells. Increased serum ApoE concentration was observed. Liquid chromatography-tandem mass spectrometry of laser-microdissected glomeruli from paraffin sections revealed an increase in ApoE. Direct deoxyribonucleic acid sequencing of ApoE revealed a heterozygous ApoE Sendai mutation (Arg145Pro). The patient was finally diagnosed with LPG with heterozygosity for ApoE-Sendai mutation (Arg145Pro). Notably, at the time of diagnosis, he had markedly increased arterial stiffness for his age. Arterial stiffness was measured using brachial-ankle pulse wave velocity (baPWV), which was equivalent to that of a 56-year-old man. After three months of treatment with fenofibrate and losartan, a significant reduction in proteinuria was achieved along with an improvement in baPWV. Furthermore, these effects were maintained despite the lack of decrease in serum ApoE levels.ConclusionHerein, we report the case of a patient with LPG with markedly increased arterial stiffness at the time of diagnosis, in whom combination therapy with fenofibrate and losartan successfully improved proteinuria and arterial stiffness. To the best of our knowledge, this is the first case report of LPG in which CVD risk was assessed using arterial stiffness.

INDEX ASSESSMENT OF PERIODONTAL TISSUES AND DETERMINATION OF TREATMENT NEEDS IN PATIENTS WITH CHRONIC RHEUMATIC HEART DISEASE

This study addresses the pressing scientific and practical issue in modern dentistry: enhancing dental care effectiveness for patients with chronic rheumatic heart disease. The purpose of this research is to comprehensively assess the condition of tooth-supporting tissues and quantify inflammatory phenomena in periodontal tissues among patients with chronic rheumatic heart disease, as well as to determine the necessary extent of periodontal care based on periodontal indices. Participants and methods. The periodontal tissues of 719 patients with chronic rheumatic heart disease from the Rheumatology Department of Lviv Regional Clinical Hospital, along with 290 clinically healthy individuals in the comparison group, were examined. To evaluate the clinical course of dystrophic-inflammatory periodontal diseases in patients with chronic rheumatic heart disease, we examined 267 individuals in the main group who had generalized periodontitis, categorized as follows: 42 patients with initial stage (I degree), 115 with moderate (II degree), and 110 with severe (III degree) periodontitis. The comparison group comprised 70 patients diagnosed with generalized periodontitis, among them, 21 had initial-stage disease, 29 had moderate-stage disease, and 20 had severe-stage disease. During the analysis, the oral hygiene was assessed by applying hygienic indices by J.C. Green and J.R. Vermillion (OHI-S, 1964) and Fedorov-Volodkina. The Muhlemann and Son index was used to objectively measure gingival papillary bleeding (RVI); the papillary-marginal-alveolar index (PMA) in the Parma modification, in combination with the Schiller-Pysarev test (1989), was employed to evaluate gingival inflammation. The periodontal index (PI) by A.L. Russel (1956) was used to assess the state of periodontal tissues, and pathological changes were recorded using the periodontal screening PSR test. Results were scored, and based on established criteria and scores, the need for treatment and its extent were determined. Results and discussion. According to the results of dental examinations in patients with chronic rheumatic heart disease, a high prevalence of periodontal diseases was found, reaching 92.49%. This was 13.18% higher compared to the prevalence in the control group. Dystrophic-inflammatory conditions with advanced severity levels were predominant, as evidenced by the index indicators. In chronic rheumatic heart disease patients, the average periodontal index was 6.11±0.10, compared to 4.14±0.19 in clinically healthy individuals (p &lt; 0.05). Moreover, a higher lesion of periodontal tissues was observed in younger age groups. As the duration of rheumatic disease increased, the frequency of detecting generalized periodontitis also increased, with this condition being diagnosed in all subjects with a 10-year history of rheumatic disease. Conclusion. The Analysis of the research data on the condition of periodontal tissues, along with objective index assessments, reveals the following: periodontal diseases are more prevalent in individuals with chronic rheumatic heart disease, particularly affecting younger age groups. The severity and progression of these diseases are influenced by the course of the underlying condition. This underscores the presence of pathogenetic conditions that contribute to the rapid progression of the dystrophic-inflammatory process in periodontal tissues. It also emphasizes the importance of providing specialized periodontal care to patients with chronic rheumatic heart disease, with the level of care directly linked to the course and duration of the systemic disease.

Phenotypic and genetic analysis of children with unexplained neurodevelopmental delay and neurodevelopmental comorbidities in a Chinese cohort using trio-based whole-exome sequencing

BackgroundTrio-based whole-exome sequencing (trio-WES) enables identification of pathogenic variants, including copy-number variants (CNVs), in children with unexplained neurodevelopmental delay (NDD) and neurodevelopmental comorbidities (NDCs), including autism spectrum disorder (ASD), epilepsy, and attention deficit hyperactivity disorder. Further phenotypic and genetic analysis on trio-WES-tested NDD-NDCs cases may help to identify key phenotypic factors related to higher diagnostic yield of using trio-WES and novel risk genes associated with NDCs in clinical settings.MethodsIn this study, we retrospectively performed phenotypic analysis on 163 trio-WES-tested NDD-NDCs children to determine the phenotypic differences between genetically diagnosed and non-genetically diagnosed groups. Additionally, we conducted genetic analysis of ASD genes with the help of Simons Foundation for Autism Research Institute (SFARI) Gene database to identify novel possible ASD-risk genes underlying genetic NDD conditions.ResultsAmong these 163 patients, pathogenic variants were identified in 82 cases (82/163, 50.3%), including 20 cases with CNVs. By comparing phenotypic variables between genetically diagnosed group (82 cases) and non-genetically diagnosed group (81 cases) with multivariate binary logistic regression analysis, we revealed that NDD-NDCs cases presenting with severe-profound NDD [53/82 vs 17/81, adjusted-OR (95%CI): 4.865 (2.213 – 10.694), adjusted-P < 0.001] or having multiple NDCs [26/82 vs 8/81, adjusted-OR (95%CI): 3.731 (1.399 – 9.950), adjusted-P = 0.009] or accompanying ASD [64/82 vs 35/81, adjusted-OR (95%CI): 3.256 (1.479 – 7.168), adjusted-P = 0.003] and head circumference abnormality [33/82 vs 11/81, adjusted-OR (95%CI): 2.788 (1.148 – 6.774), adjusted-P = 0.024] were more likely to have a genetic diagnosis using trio-WES. Moreover, 37 genes with monogenetic variants were identified in 48 patients genetically diagnosed with NDD-ASD, and 15 dosage-sensitive genes were identified in 16 individuals with NDD-ASD carrying CNVs. Most of those genes had been proven to be ASD-related genes. However, some of them (9 genes) were not proven sufficiently to correlate with ASD. By literature review and constructing protein-protein interaction networks among these 9 candidate ASD-risk genes and 102 established ASD genes obtained from the SFARI Gene database, we identified CUL4B, KCNH1, and PLA2G6 as novel possible ASD-risk genes underlying genetic NDD conditions.ConclusionsTrio-WES testing is recommended for patients with unexplained NDD-NDCs that have severe-profound NDD or multiple NDCs, particularly those with accompanying ASD and head circumference abnormality, as these independent factors may increase the likelihood of genetic diagnosis using trio-WES. Moreover, NDD patients with pathogenic variants in CUL4B, KCNH1 and PLA2G6 should be aware of potential risks of developing ASD during their disease courses.

Effects of intensive psychological intervention on treatment compliance, psychological status, and quality of life of patients with epilepsy

BACKGROUND Epilepsy is a nervous system disease characterized by recurrent attacks, a long disease course, and an unfavorable prognosis. It is associated with an enduring therapeutic process, and finding a cure has been difficult. Patients with epilepsy are predisposed to adverse moods, such as resistance, anxiety, nervousness, and anxiety, which compromise treatment compliance and overall efficacy. AIM To explored the influence of intensive psychological intervention on treatment compliance, psychological status, and quality of life (QOL) of patients with epilepsy. METHODS The clinical data of 105 patients with epilepsy admitted between December 2019 and July 2023 were retrospectively analyzed, including those of 50 patients who underwent routine intervention (control group) and 55 who underwent intensive psychological intervention (research group). Treatment compliance, psychological status based on the Self-Rating Anxiety Scale (SAS) and Depression Scale Self-Rating Depression Scale (SDS) scores, hope level assessed using the Herth Hope Scale (HHS), psychological resilience evaluated using the Psychological Resilience Scale, and QOL determined using the QOL in Epilepsy-31 Inventory (QOLIE-31) were comparatively analyzed. RESULTS Treatment compliance in the research group was 85.5%, which is significantly better than the 68.0% of the control group. No notable intergroup differences in preinterventional SAS and SDS scores were identified (P &gt; 0.05); however, after the intervention, the SAS and SDS scores decreased significantly in the two groups, especially in the research group (P &lt; 0.05). The two groups also exhibited no significant differences in preinterventional HHS, Connor-Davidson Resilience Scale (CD-RISC), and QOLIE-31 scores (P &gt; 0.05). After 6 months of intervention, the research group showed evidently higher HHS, CD-RISC, tenacity, optimism, strength, and QOLIE-31 scores (P &lt; 0.05). CONCLUSION Intensive psychological intervention enhances treatment compliance, psychological status, and QOL of patients with epilepsy.

TOLL-LIKE RECEPTORS AND BRONCHIAL ASTHMA: PART 1

Bronchial asthma is a chronic disease of the respiratory tract, which is formed by the action of endogenous factors and environmental influences. At the same time, T-helpers of the second type play a major role in the development of bronchial asthma, causing hyperreactivity and inflammation of the respiratory tract. However, the data that bronchial asthma in most cases is an allergic, eosinophilic, T-helper-mediated disease of the second type is insufficient to establish complete control over the course of disease. This is probably due to the fact that endogenous factors play an important role in the pathogenesis of asthma, knowledge of which is currently limited. Toll-like receptors are an established element of the development of bronchial asthma. Their insufficient function or, conversely, the launch of an excessive immune response is associated with the initiation of the disease or its exacerbations. Expanding the understanding of Toll-like receptors leads not only to a more detailed understanding of the pathogenesis of bronchial asthma, but also to the application of this knowledge in practice.

Impact on survival without chemotherapy of local treatments of lung metastasis of colorectal cancers: Analysis on REPULCO cohort.

The impact of local management of pulmonary metastases on the disease course of patients with metastatic colorectal cancer is poorly assessed. REPULCO database was a retrospective cohort on 18 years that included all patients treated for lung metastases from colorectal cancer who received local and/or systemic treatments. Primary objective was overall survival, secondary were progression-free survival and survival without chemotherapy. Three hundred and fifteen patients were analyzed, 157 with only systemic treatments, 78 with only local treatments, and 80 with local and systemic treatments. Overall survival at 5 years was 26.9% (IC95%: [17.7-36.9]) for systemic treatments only, 61.0% (IC95%: [40.8-76.1]) for local treatments only, and 77.8% (IC95%: [60.1-88.3]) for local and systemic treatments. Progression-free survival at 2 years was 4.8% (IC95%: [2.1-9.2]) for systemic treatment only, 28.3% (IC95%: [17.7-39.9]) for local treatments only, and 21.8% (IC95%: [13.1-31.9]) for local and systemic treatments. Median survival without chemotherapy was 2.99 months (IC95%: [2.33-3.68]) for systemic treatments, 33.97 months (IC95%: [19.06-NA]) for local treatments, and 12.85 months (IC95%: [8.18-21.06]) for local and systemic treatments. Local treatments of lung metastasis led to prolonged survival and allowed long periods of time without chemotherapy in this cohort.

4-Octyl Itaconate Attenuates Neuroinflammation in Experimental Autoimmune Encephalomyelitis Via Regulating Microglia.

Abnormal activation of microglia, the resident macrophages in the central nervous system, plays an important role in the pathogenesis of multiple sclerosis (MS). The immuneresponsivegene1(IRG1)/itaconate axis is involved in regulating microglia-mediated neuroinflammation. 4-Octyl itaconate (4-OI), a derivative of itaconate, plays a crucial immunomodulatory role in macrophages. This study investigated the effects and mechanisms of action of 4-OI on experimental autoimmune encephalomyelitis (EAE) and inflammatory BV2 microglia.In an EAE mouse model, clinical evaluation was conducted during the disease course. Hematoxylin and eosin staining was performed to assess inflammatory infiltration and Luxol Fast Blue was used to visualize pathological damage. Quantitative real-timepolymerase chain reaction, western blotting and immunofluorescence were used to evaluate inflammatory response and microglial function status in EAE mice. BV2 microglia were used to further investigate the effects and mechanisms of action of 4-OI in vitro.4-OI significantly alleviatedthe clinicalsymptoms of EAE, the inflammatory infiltration, and demyelination; reduced the levels of inflammatory factors; and inhibited the classical activation of microglia in the spinal cord. 4-OI successfully suppressed the classical activation of BV2 microglia and decreased the levels of inflammatory factors by activating the Nrf2/HO-1 signaling pathway. Furthermore, 4-OI downregulated IRG1 expression in both EAE mice and inflammatory BV2 microglia. 4-OI attenuates the microglia-mediated neuroinflammation and has promising therapeutic effects in MS.

Impact of HLA-B51 on Uveitis and Retinal Vasculitis: Data from the AIDA International Network Registries on Ocular Inflammatory Disorders.

The clinical relevance of human leukocyte antigen (HLA) subtypes such as HLA-B51 on Behçet's disease (BD)-related uveitis and non-infectious uveitis (NIU) unrelated to BD remains largely unknown. Data were prospectively collected from the International AIDA Network Registry for BD and for NIU. We assessed differences between groups (NIU unrelated to BD and positive for HLA-B51, BD-related uveitis positive for HLA-B51 and BD-related uveitis negative for HLA-B51) in terms of long-term ocular complications, visual acuity (VA) measured by best corrected visual acuity (BCVA), anatomical pattern, occurrence of retinal vasculitis (RV) and macular edema over time. Records of 213 patients (341 eyes) were analyzed. No differences in complications were observed (p = 0.465). With regard to VA, a significant difference was detected in median BCVA (p = 0.046), which was not maintained after Bonferroni correction (p = 0.060). RV was significantly more prevalent in NIU-affected patients who tested positive for HLA-B51, irrespective of the systemic diagnosis of BD (p = 0.025). No differences emerged in the occurrence of macular edema (p = 0.99). Patients with NIU testing positive for HLA-B51 exhibit an increased likelihood of RV throughout disease course, irrespective of a systemic diagnosis of BD. The rate of complications as well as VA are comparable between NIU cases unrelated to BD testing positive for HLA-B51 and uveitis associated with BD. Therefore, it is advisable to perform the HLA-B typing in patients with NIU or retinal vasculitis, even in the absence of typical BD features.

The natural history of eosinophilic gastrointestinal diseases is influenced by age of onset and location of involvement.

It is unknown whether concomitant esophageal involvement or anatomic location of eosinophilic infiltration impact the natural history of eosinophilic gastrointestinal disease (EGID). A retrospective cohort study was performed utilizing the University of North Carolina EGID Clinicopathologic Database. Patients were adults and children with a prior EGID diagnosis based on clinicopathologic features. Demographics, clinical characteristics, treatment information, and procedural data were extracted from medical records. Clinical course and flare history were characterized. Among 97 patients, 43% had EGID+esophageal involvement and 57% had EGID only. Patients with esophageal involvement had a longer diagnostic delay preceding diagnosis (36.6 vs 11.6 months, p=0.001), more dysphagia (50% vs 18%; p=0.001), required more chronic therapy (77% vs 52%, p=0.016), and exhibited more progressive disease (25% vs 6%, p=0.027). A continuous disease course was most common in EoG (78%), while EoG+EoN (29%) and EoN+EoC (50%) patients had the highest proportion of progressive and relapsing disease, respectively (p=0.045). A continuous disease course occurred more frequently in children (71%, p=0.03) and those with single organ involvement (65%), whereas adults had more relapsing (39%) or progressive disease (18%). EGIDs with and without esophageal involvement display many similarities, although patients with esophageal involvement more frequently had dysphagia, progressive disease courses, and required more chronic therapy. Location of involvement and age at onset impacted the natural history with higher proportions of relapsing or progressive disease seen in adults and patients with small bowel or multiorgan involvement, while a continuous disease course was more common in children and patients with gastric-only involvement.

An overview of prognostic markers in patients with CLL

Chronic lymphocytic leukemia (CLL) is a low-grade B-cell lymphoproliferative disorder. It is the most prevalent type of leukemia in the western countries, with a median age at diagnosis of 70 years. In 2023, it is estimated that there will be 18,740 new cases of CLL, and an estimated 4,490 people will die of this disease. It represents 1.0% of all new cancer cases in the U.S. The rate of new cases was 4.6 per 100,000 men and women per year based on 2016–2020 cases, age-adjusted. Death rates from CLL are higher among older adults, or those 75 and older. The death rate was 1.1 per 100,000 men and women per year based on 2016–2020 deaths, age-adjusted. A common question that patients with CLL ask during their first clinic visit is: “How long will it be before I would need treatment?” Although this might seem like a simple question, the answer is not straight forward. CLL is a heterogenous disease, with a variable clinical course. Some patients may present with an aggressive disease requiring early initiation of treatment, while others have an indolent course and some, having so called smoldering CLL, may never need treatment. The variability in disease course can make predicting disease prognosis a complicated process. This brings forth the importance of establishing prognostic models that can predict disease course, time to treatment, and survival outcomes in such a heterogenous disease. The Rai and Binet staging systems were developed in the late 1970s to early 1980s. They separated patients into different stages based on clinical characteristics and laboratory findings. These simple staging systems are still in use; however, several prognostic markers need to be added for an individualized assessment and, with the recent development of genomic techniques leading to better understanding of CLL at the molecular level, newer prognostic markers have emerged.

Blood purification therapy in chronic renal failure and its impact on renal index, serological index, and inflammatory factors

Introduction: This study aimed to explore the clinical effects of blood purification therapy in patients with chronic renal disease, measured by renal function index and inflammation. Methodology: Data were collected from a tertiary care hospital in Pakistan between June 2022 and September 2023. 84 patients undergoing maintenance hemodialysis for chronic renal failure were retrospectively included in this cohort. Results: Age, sex, body mass index (BMI), course of disease, primary disease, and educational level were not related to the response to blood purification treatment. Blood purification therapy positively affected renal function, serological indices, and inflammatory factors (P&lt;0.05). Conclusion: Blood purification therapy can improve toxin clearance and renal function and reduce inflammation. Therefore, we can conclude that this is an effective therapy for our population.

Depression proteomic profiling in adolescents with transcriptome analyses in independent cohorts

IntroductionDepression is a major global burden with unclear pathophysiology and poor treatment outcomes. Diagnosis of depression continues to rely primarily on behavioral rather than biological methods. Investigating tools that might aid in diagnosing and treating early-onset depression is essential for improving the prognosis of the disease course. While there is increasing evidence of possible biomarkers in adult depression, studies investigating this subject in adolescents are lacking.MethodsIn the current study, we analyzed protein levels in 461 adolescents assessed for depression using the Development and Well-Being Assessment (DAWBA) questionnaire as part of the domestic Psychiatric Health in Adolescent Study conducted in Uppsala, Sweden. We used the Proseek Multiplex Neuro Exploratory panel with Proximity Extension Assay technology provided by Olink Bioscience, followed by transcriptome analyses for the genes corresponding to the significant proteins, using four publicly available cohorts.ResultsWe identified a total of seven proteins showing different levels between DAWBA risk groups at nominal significance, including RBKS, CRADD, ASGR1, HMOX2, PPP3R1, CD63, and PMVK. Transcriptomic analyses for these genes showed nominally significant replication of PPP3R1 in two of four cohorts including whole blood and prefrontal cortex, while ASGR1 and CD63 were replicated in only one cohort.DiscussionOur study on adolescent depression revealed protein-level and transcriptomic differences, particularly in PPP3R1, pointing to the involvement of the calcineurin pathway in depression. Our findings regarding PPP3R1 also support the role of the prefrontal cortex in depression and reinforce the significance of investigating prefrontal cortex-related mechanisms in depression.

The Molecular Basis of Olfactory Dysfunction in COVID-19 and Long COVID.

Olfactory dysfunction (OD) is not uncommon following viral infection. Herein, we explore the interplay of host genetics with viral correlates in coronavirus disease 2019 (COVID-19)- and long COVID-related OD, and its diagnosis and treatment that remain challenging. Two genes associated with olfaction, UGT2A1 and UGT2A2, appear to be involved in COVID-19-related anosmia, a hallmark symptom of acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), particularly in the early stages of the pandemic. SARS-CoV-2 infects olfactory support cells, sustentacular and Bowman gland cells, that surround olfactory sensory neurons (OSNs) in the olfactory epithelium (OE) where the initial step of odor detection takes place. Anosmia primarily arises from the infection of support cells of the OE, followed by the deciliation and disruption of OE integrity, typically without OSN infection. Through the projected axons of OSNs, the virus could theoretically reach the olfactory bulb and brain, but current evidence points against this route. Intriguingly, SARS-CoV-2 infection of support cells leads to profound alterations in the nuclear architecture of OSNs, leading to the downregulation of odorant receptor-related genes, e.g., of Adcy3. Viral factors associated with the development of OD include spike protein aminoacidic changes, e.g., D614G, the first substitution that was selected early during SARS-CoV-2 evolution. More recent variants of the Omicron family are less likely to cause OD compared to Delta or Alpha, although OD has been associated with a milder disease course. OD is one of the most prevalent post-acute neurologic symptoms of SARS-CoV-2 infection. The tens of millions of people worldwide who have lingering problems with OD wait eagerly for effective new treatments that will restore their sense of smell which adds value to their quality of life.