Course Of Disease Research Articles

Association of Initial Side of Brain Atrophy With Clinical Features and Disease Progression in Patients With GRN Frontotemporal Dementia.

Pathogenic variants in the GRN gene cause frontotemporal dementia (FTD-GRN) with marked brain asymmetry. This study aims to assess whether the disease progression of FTD-GRN depends on the initial side of the atrophy. We also investigated the potential use of brain asymmetry as a biomarker of the disease. Retrospective examination of data from the prospective Genetic Frontotemporal Initiative (GENFI) cohort study that recruits individuals who carry or were at risk of carrying a pathogenic variant causing FTD. GENFI participants underwent a standardized clinical and neuropsychological assessment, MRI, and a blood sample test yearly. We generated an asymmetry index for brain MRI to characterize brain asymmetry in participants with or at risk of FTD-GRN. Depending on the side of the asymmetry, we classified symptomatic GRN patients as right-GRN or left-GRN and compared their clinical features and disease progression. We generated generalized additive models to study how the asymmetry index evolves in carriers and noncarriers and compare its models with others created with volumetric values and plasma neurofilament light chain. A total of 399 participants (mean age 49.7 years, 59% female) were included (63 symptomatic carriers, 177 presymptomatic carriers, and 159 noncarriers). Symptomatic carriers showed higher brain asymmetry (11.6) than noncarriers (1.0, p < 0.001) and presymptomatic carriers (1.0, p < 0.001), making it possible to classify most of them as right-GRN (n = 21) or left-GRN (n = 36). Patients with right-GRN showed more disease severity at baseline (β = 6.9, 95% CI 2.4-11.0, p = 0.003) but a lower deterioration by year (β = -1.5, 95% CI -2.7 to -0.31, p = 0.015) than patients with left-GRN. Brain asymmetry could be found in GRN carriers 10.4 years before the onset of the symptoms (standard difference 0.85, CI 0.01-1.68). FTD-GRN affects the brain hemispheres asymmetrically and causes 2 anatomical asymmetry patterns depending on the side of the disease onset. We demonstrated that these 2 anatomical asymmetry patterns present different symptoms, severity at the time of the first visit, and different disease courses. Our results also suggest brain asymmetry as a possible biomarker of conversion in GRN carriers.

Evaluating renal disease in pediatric-onset anti-neutrophil cytoplasmic antibody-associated vasculitis: disease course, outcomes, and predictors of outcome.

We aimed to study the disease course, outcomes, and predictors of outcome in pediatric-onset anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) affecting the kidneys. Patients eligible for this study had a diagnosis of granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), or ANCA positive pauci-immune glomerulonephritis, were ≤ 18 years at diagnosis, had renal disease defined by biopsy or dialysis dependence, and had clinical data at diagnosis and either 12- or 24-months. Ambispective data from the ARChiVE/PedVas Registry was used. The primary outcome was inactive renal disease (PVAS = 0 or 1) at 12-months. Secondary outcomes included rates of improved renal function and damage within 24-months. Renal function, defined by estimated glomerular filtration rate (eGFR), was categorized into KDIGO (Kidney Disease Improving Global Outcomes) stages at diagnosis and tested as a predictor of outcome using a proportional odds logistic regression model. 145 patients were included. 68% were female, 78% had GPA. At 12-months, 83% of patients achieved inactive renal disease; however, 42% had evidence of permanent renal damage. Compared to patients with normal renal function at diagnosis, patients with moderate-to-severely reduced renal function, or kidney failure at diagnosis had an odds ratio of 8.62 (p=0.002, 95% CI: 2.31, 32.1) and 26.3 (p <0.001, 95% CI: 6.32, 109), respectively, for being in a worse KDIGO category at 12-months. The majority of pediatric-AAV patients achieve inactive renal disease by 12-months; however, almost half have evidence of damage. Renal function at diagnosis is a strong predictor of renal function at 12-months.

Obesity: Friend or Foe in Sjögren’s Syndrome Patients?

Background/Objectives: In Sjögren’s syndrome, exocrine glands are destructed in an autoimmune-mediated process. Obesity is known to influence a wide range of diseases. This study aimed to examine whether obesity has an impact on the disease course of our patients with Sjögren’s syndrome. Methods: Out of the regularly followed-up patients, 125 were grouped based on their body mass index (BMI). Below a BMI of 25, they were listed as “non-obese” (n = 45), whereas above a BMI of 25, they were categorized as “obese” (n = 80). Demographic, laboratory, and immunological parameters; Sjögren’s syndrome disease activity index; certain extraglandular manifestations; and treatment modalities were compared using biostatistical methods. Results: Among the examined cardiovascular and cerebrovascular co-morbidities, type 2 diabetes and hypertension were significantly more frequent in the obese group. Considering the associated further autoimmune disorders and extraglandular manifestations, in our patients, there were no significant differences between the two groups. Among laboratory parameters, gamma glutamil transferase, alanine transaminase, hemoglobin, hematocrit, lymphocyte rate, triglyceride, and c3 and c4 complement levels were significantly higher in the obese group, while the proportion of rheumatoid factor positivity and the neutrophil granulocyte rate were significantly lower. Immunoglobulin G, A, and M levels did not differ significantly between the two subsets. Obese patients needed steroid therapy significantly less frequently; however, statin therapy was remarkably more frequent in that group. Furthermore, the European League Against Rheumatism (EULAR) Sjögren’s syndrome disease activity index (ESSDAI) was significantly lower in the group of overweight patients. Conclusions: Our results suggest that several immunological parameters of obese patients are more favorable compared to those with normal body weight. Behind that, we might suspect either the beneficial effect of statin therapy and/or the obesity paradox.

Glucocorticoid treatment for primary and secondary central nervous system vasculitis

Although the first-line treatment of central nervous system vasculitis (CNSV) is glucocorticoids (GC), the duration and dose of GC is still unknown. Although CNSVs seem to be a disease limited to a single area, they are a heterogeneous group of diseases clinically, in terms of involvement pattern and course. Due to the highly heterogeneous nature of the disease, patient-specific determination of the initial dose of GC is essential. Considering the disease courses, it may be more appropriate to consider 1mg/kg oral GC treatment if small/distal vessels are involved and intravenous bolus GC treatment if large/proximal vessels are involved in primary-CNSVs. In secondary-CNSVs (Anca-associated vasculitis, Behçet’s syndrome, Systemic Lupus Erythematosus) intravenous high dose GC treatment is recommended.

Endovascular treatment of non-acute symptomatic anterior circulation distal medium artery disease

Objective: To examine the clinical effect of endovascular treatment for patients with non-acute symptomatic anterior circulation distal medium artery disease (aDMAD). Methods: This is a retrospective case series study.Retrospective analysis was conducted on the clinical data of 28 patients(29 lesions) with non-acute symptomatic aDMAD who underwent endovascular treatment at the Department of Neurosurgery,Beijing Hospital from May 2018 to March 2024. There were 15 males and 13 females,with an age of (63.4±10.2) years (range:36 to 82 years). The course of disease were more than 72 hours of all the patients. Confirmed by digital subtraction angiography,the lesion was located in distal anterior circulation and (or) medium arteries. Among them, 21 lesions (72.4%) located at middle cerebral artery and 8 lesions (27.6%) located at anterior cerebral artery.The median degree of stenosis before surgery (M(IQR)) was 90%(23%) (range:70% to 100%).After standardized drug treatment,there was still a transient ischemic attack or cerebral infarction in the vascular related area.The therapeutic effects and complications were analyzed,and the differences in the occurrence of target vessel restenosis under different interventional treatment methods were collected. Results: A total of 28 patients with 29 lesions underwent endovascular treatment, with a treatment success rate of 96.6% (28/29). The course of disease was 60(66)days (range:9 to 210 days). Simple plain balloon angioplasty was performed in 12 cases (13 lesions), drug-coated balloon (DCB) angioplasty in 7 cases (7 lesions), and stent placement in 9 cases (9 lesions). The median degree of stenosis after surgery was 20%(39%) (range:0 to 50%). There was no new cerebral infarctions,cerebral hemorrhages,or other complications during the perioperative period.Imaging follow-up was conducted on 23 lesions for 12(15)months(range:3 to 34 months),with 10 cases (43.5%) of restenosis,3 cases (13.0%) of symptomatic restenosis,and 4 cases (17.4%) of re-treatment. There were no new cases of cerebral hemorrhage or death during the follow-up process.The restenosis rate was 6/10 for the conventional balloon group,1/6 for the DCB group, and 3/7 for the stent group; the rate of symptomatic restenosis was 1/10 for the conventional balloon group,0/6 for the DCB group, and 2/7 for the stent group. Conclusions: Endovascular treatment for non-acute symptomatic aDMAD is relatively effective,but there is a high rate of restenosis postoperatively. DCB may reduce the occurrence of postoperative restenosis.

Study on the value of enhanced magnetic resonance imaging in the International Prophylaxis Study Group (IPSG) score of the synovium in hemophilic arthropathy

Objective: To evaluate the value of enhanced magnetic resonance imaging (MRI) on the assessment of synovial hyperplasia and International Prophylaxis Study Group (IPSG) score of hemophilic arthropathy (HA). Methods: This was a retrospective case series study. Briefly, 54 joints of 46 male patients with hemophilia type A and diagnosed with HA in Henan Provincial People's Hospital from August 2016 to September 2017 were selected. Plain and enhanced MRI were performed at the same time. The IPSG score of synovial hyperplasia and the total joint before and after enhancement were calculated, and the enhancement rate of the synovium and muscles at the same level were also calculated. The differences in synovial hyperplasia and joint total IPSG scores before and after enhancement were compared by paired rank sum test. The correlation between enhancement joint total IPSG score, synovial IPSG score, synovial enhancement rate, total joint bleeding number, course of disease, and Hemophilia Joint Health Score (HJHS) score were analyzed by Spearman's correlation analysis. Results: Enhanced MRI could more clearly show synovial hyperplasia and ensure better accuracy of joint total IPSG score (Z=-2.24, P=0.025). The enhancement extent of synovial hyperplasia was higher than that of the same level muscle. There was no correlation between synovial enhancement rate and total number of joint bleeding, course of disease, and HJHS score. After enhancement, the joint total IPSG score was highly positively correlated with the total number of joint bleeding and the disease course (r=0.96, 0.84, P<0.001) and moderately positively correlated with the HJHS score (r=0.58, P<0.001). The enhanced synovial IPSG score showed a low positive correlation with the total number of joint bleeding and the disease course (r=0.37, 0.36, P=0.006, 0.008), but no correlation with HJHS score. Conclusion: Enhanced MRI can provide accurate imaging of synovial hyperplasia of HA and make joint IPSG score more accurate.

Clinical features of 50 patients with primary intestinal lymphangiectasia

Objective: To investigate the clinical features of primary intestinal lymphangiectasia (PIL). Methods: This study was a retrospective case series study. Fifty consecutive patients diagnosed with PIL in Department of Lymphatic Surgery, Beijing Shijitan Hospital, Capital Medical University from March 2019 to March 2021 were included and their clinical data was retrospectively reviewed. There were 20 males and 30 females included, with an age of (M(IQR)) 14 (40) years (range:0 to 67 years). No patient had the family history. There were 26 children, including 9 males and 17 females, aged 0 (7) years (range:0 to 14 years). There were 24 adults, including 11 males and 13 females, aged 40 (26) years (range:20 to 67 years). The clinical manifestations and the results of laboratory examinations, gastrointestinal endoscopy, 99Tcm-labeled human albumin (99Tcm-HSA) scintigraphy, 99Tcm-DX scintigraphy, direct lymphangiography (DLG), histopathology, diet treatment, surgical intervention, and clinical symptom remission at discharge were collected. Comparisons between groups were performed using independent samples t-test, Mann-Whitney U test, or χ 2 test. Results: Among the 50 cases of PIL, the main manifestations were edema (86.0%), diarrhea (76.0%), and abdominal effusion (48.0%). Lymphedema (36.0%) and chylous ascites (18.0%) were not rare in PIL patients. In 99Tcm-HAS scintigraphy, 95.9% (47/49) cases showed signs of intestinal protein loss, and 91.7% (44/48) ceses showed positive findings in 99Tcm-DX scintigraphy. In DLG, 97.8% (45/46) cases showed signs of thoracic duct obstruction, 82.6% (38/46) cases showed retroperitoneal lymphatic hyperplasia, and 23.9% (11/46) cases showed backflow of contrast agent into intestine. No significant difference was seen in gender, course of disease, clinical manifestation, serum level of albumin or globulin, lymphocyte count, positive rate of fecal occult blood and prevalence of lymphedema between adults and children (all P>0.05). Conclusions: The clinical presentations of PIL between children and adults had no significant difference. The diagnosis of PIL should be made according to clinical manifestation, 99Tcm-HAS scintigraphy, 99Tcm-DX scintigraphy, DLG, gastrointestinal endoscopy and pathological findings.

Management of pediatric thyroid carcinoma.

The incidence of thyroid carcinoma is increasing among children and adolescents, particularly in female individuals. Children and adolescents require special considerations in management as the molecular genetics of pediatric thyroid tumors are inherently different from their adult counterparts. The increased risk of malignancy, nodal metastases, and pulmonary metastases in pediatric patients warrants pediatric-specific management recommendations and pediatric-specific multidisciplinary teams. This article highlights the molecular origins of pediatric thyroid carcinoma and the implications of tumor genetics for the course of disease and treatment considerations. We highlight specific surgical considerations to optimize outcomes while minimizing lifelong risks of vocal paralysis and hypoparathyroidism. The landscape of treatment options is rapidly evolving with development of sophisticated molecular approaches to understand the genetic landscape, and this review features updated recommendations and systemic treatment options for the management of pediatric thyroid malignancy. Pediatric thyroid carcinoma is a lifelong burden and the treatment tailored to optimize outcomes minimizes long-term risks of treatments, surgery, radiation and targeted systemic therapies. Multidisciplinary teams that treat pediatric thyroid carcinoma should focus surgical experience and use the most updated guidelines and treatments available, particularly considering the landscape of molecular genetics in pediatric thyroid carcinoma.

Long-Term Seizure Outcome With or Without Vagal Nerve Stimulation Therapy.

To compare long-term seizure control in patients with long-term VNS (vagal nerve stimulator) stimulation (VNS-on) with those who discontinued VNS after >3 years (VNS-off). Patients with refractory epilepsy with VNS therapy for >3 years (and follow-up for >2 years after VNS discontinuation for VNS-off patients) were included. Patients with brain surgery <3 years after VNS were excluded. We compared the percentage of patients with ≥50% seizure reduction (50% responder rate) and change in seizure frequency within and between groups in follow-up. Thirty-three VNS-on and 16 VNS-off patients were evaluated. VNS-on patients underwent stimulation for 9.7 years (mean). VNS-off patients had VNS treatment for 6.5 years (mean), discontinued treatment, then had additional 8.0 years (mean) follow-up. 50% responder rates were similar between groups (VNS-on: 54.5% vs VNS-off at last-on: 37.5%, p = 0.26; vs VNS-off at the last follow-up: 62.5%, p = 0.60). VNS-on patients had a significant reduction in seizure frequency at the last follow-up compared with baseline (median [Mdn] = -4.5 seizures/month, interquartile range [IQR] = 14.0, 56% reduction, p = 0.013). VNS-off patients also showed significant seizure reduction while still continuing VNS therapy (Mdn = -1.0 seizures/month, IQR = 13.0, 35% reduction, p = 0.020) and, after discontinuing therapy, at the last follow-up compared with baseline (Mdn = -3.2, IQR = 11.0, 52% reduction, p = 0.020). The 2 groups were comparable in seizure frequency change both at the last-on visit (absolute change, p = 0.62; relative change, p = 0.50) at the last follow-up (absolute change, p = 0.67; relative change, p = 0.76). Patients who discontinued VNS therapy and those who continued therapy had similar response during active treatment and similar long-term outcomes, suggesting that factors such as the natural disease course and/or medication treatment strongly affect long-term outcomes.

A Novel MYH14 Variant Presenting as a New Phenotype of MYH14-Associated Neuromuscular Disorders—Clinicohistologic Findings and Review of the Literature

Abstract Background: Pathogenic variants in the nonmuscle myosin, MYH14, have been associated with several pathologic conditions including a complex phenotype with peripheral neuropathy, myopathy, hoarseness, and hearing loss. Since its first description in a large Korean kindred, this rare neuromuscular disorder has further been characterized in 1 American and 1 Canadian pedigree. Case presentation: Here, we describe a German patient with atypical MYH14-related neuromuscular disorder. The clinical phenotype included signs of a distal myopathy with early respiratory involvement and a prominent hoarseness and peripheral neuropathy. In contrast to previous reports, no relevant deafness was identified. Muscle biopsy indicated a vacuolated myopathy with excessive autophagy, whereas histology of the sural nerve showed signs of a mixed axonal-demyelinating neuropathy. Next-generation sequencing revealed a loss-of-function variant not identified so far in the MYH14 gene (c.4510del, p.[Arg1504Glyfs*10]). Because of rapid disease progression with respiratory failure, the patient died at the age of 52. Conclusions: We present a novel MYH14 variant resulting in a severe and rapidly progressive MYH14-associated phenotype with predominantly distal myopathy, early respiratory failure, dysphagia, hoarseness, and peripheral neuropathy, without hearing loss. This case expands the clinical spectrum of MYH14-related neuromuscular disorders by providing a new clinical phenotype and disease course and histopathologic features.

CAR T-cell therapy for B-cell lymphomas: outcomes and resistance mechanisms.

Chimeric antigen receptor (CAR) T cells are an exciting curative intent approach to the treatment of non-Hodgkin lymphomas (NHLs). Several products have received FDA approval for 2nd or 3rd line indications, and studies are underway for their use earlier in the disease course. These CAR T cells are ex vivo manufactured autologous cell products that specifically target tumor antigens to optimize tumor specificity and minimize off-tumor side effects-in NHLs, this is typically achieved by targeting B-cell antigens. Engagement of the CAR and corresponding antigen is designed to result in T-cell activation and subsequent tumor clearance. While curative for many NHL patients, too many patients fail to respond to or relapse following CAR T-cell treatment, and salvage options post CAR T-cell therapy are limited. Treatment failures occur because of myriad resistance mechanisms including CAR T-cell dysfunction, generalized immune dysregulation, and intrinsic tumor resistance. Focusing on patients with NHL, we review the clinical outcomes of CAR T-cell therapy and the major resistance mechanisms that lead to poor outcomes. We also review the many innovative and encouraging strategies that are being developed to improve CAR T-cell therapy for NHL.

Missense variants in the TRPMr7 α-kinase domain are associated with recurrent pediatric acute liver failure

Background: Pediatric acute liver failure (PALF) is a rare and life-threatening condition. In up to 50% of PALF cases, the underlying etiology remains unknown during routine clinical testing. This lack of knowledge complicates clinical management and liver transplantation decisions. Recently, whole-exome sequencing has identified genetic disorders in a large number of cases without specific laboratory biomarkers or metabolic fingerprints. Methods: We describe how further analysis of whole-exome sequencing data combined with proteomic analyses in 5 previously unsolved PALF patients, where no pathogenic variants in genes previously associated with acute liver failure were identified, revealed rare biallelic variants in transient receptor potential cation channel subfamily M member 7 (TRPM7). Results: We establishe TRPM7 as a novel disease gene for PALF. Yet, the cation channel kinase TRPM7 has not been associated with any Mendelian disorder. No homozygous loss-of-function variants were found in in-house exomes or publicly available databases. Rare biallelic TRPM7-variants were significantly enriched in the PALF cohort compared with a pediatric control cohort. Viral infections preceded the majority of PALF episodes. Recurrent PALF episodes characterized the disease course with rapid progression, leading to early death in 3 cases. Proteomic analyses of patient fibroblasts unveiled significantly reduced TRPM7 protein levels, indicative of functional impairment. Severely reduced Mg2+ levels in one individual with a mutation in the channel domain suggests a potential interaction between disturbed Mg2+ homeostasis and PALF. The consistent presence of mutations in the TRPM7 protein-kinase-domain across all patients suggests its specific relevance in PALF. Conclusions: Our data extend the genetic spectrum of recurrent PALF and prompt consideration of TRPM7 in children with unexplained liver failure.

Management of primary sclerosing cholangitis: Current state-of-the-art

Primary sclerosing cholangitis is a chronic liver disease characterized by progressive inflammation and fibrosis of medium-large bile ducts, most commonly in association with inflammatory bowel disease. Most patients have a progressive disease course, alongside a heightened risk of hepatobiliary and colorectal cancer. Medical therapies are lacking, and this, in part, reflects a poor grasp of disease biology. As a result, current management is largely supportive, with liver transplantation an effective life-prolonging intervention when needed, but not one that cures disease. Emerging therapies targeting disease progression, as well as symptoms such as pruritus, continue to be explored. The trial design is increasingly cognizant of the application of thoughtful inclusion criteria, as well as better endpoints aimed at using surrogates of disease that can identify treatment benefits early. This is hoped to facilitate much-needed advances toward developing safe and effective interventions for patients.

Rheumatoid arthritis and PLA2R-associated mebranous nephropathy. Cause or coincidence?

The coexistence of rheumatoid arthritis (RA) and PLA2R-associated membranous nephropathy (MN) is uncommon. It is difficult to demonstrate whether the mechanisms of renal pathology are triggered by RA, but it has been observed that the pro-inflammatory molecules present in RA increase the expression of PLA2R. Rituximab could be effective in both conditions. RA affects 0.5% of adults in our country. It is an inflammatory disease that predominantly affects the joints causing destruction of the articular cartilage. Approximately 50% of patients present extra-articular manifestations. Renal involvement is relatively frequent and clinically significant because it worsens the course and mortality of the primary disease. The histological renal damage observed in these patients includes a wide variety of entities and histological patterns with both glomerular and tubulointerstitial involvement, with secondary MN being one of the most frequent. Coexistence with primary MN is rare. We present the case of a 46-year-old male recently diagnosed with RA who was referred to the nephrology department for renal function deterioration and subnephrotic proteinuria. The autoimmune study showed positive anti-PLA2R. Due to the unusual association between both entities, it was decided to perform a renal biopsy which showed abundant spikes. The immunofluorescence study showed contiguous parietal IgG positivity (3+). Immunohistochemistry showed positive granular IgG4, confirming the diagnosis of PLA2R-associated MN. MN is one of the most common causes of nephrotic syndrome in adults. The determination of anti-PLA2R has been a great advance in the rapid differential diagnosis of MN. In recent years, new target antigens associated with certain underlying pathologies have been discovered. However, PLA2R is not associated with any disease or exposure and therefore remains the antigen responsible for 80% of primary NMs. Anti-PLA2R antibodies can be produced by loss of central or peripheral tolerance. Whether these mechanisms are triggered by RA itself is difficult to prove. The cytokine TNF-like weak inducer of apoptosis (TWEAK) has been associated with RA. This proinflammatory molecule increases the expression of PLA2R in podocytes, sensitizing them to the damaging action of anti-PLA2Rs, which could justify a causal relationship between the two pathologies. The anti-PLA2R positivity in a patient with membranous nephropathy should not be sufficient to refrain from searching for a secondary cause, as a kidney biopsy is mandatory when another underlying disease coexists. Treatment should be tailored to the individual risk profile for progression. Rituximab could be an optimal option for both entities.

Relationships between emotional state, sleep disturbance and health-related quality of life in patients with axial spondyloarthritis.

Axial spondyloarthritis (ax-SpA) is an autoinflammatory disease affecting multiple organs. While emphasizing the treatment of chronic diseases, it has been found that the prevalence of mental disorders and insomnia in patients is also increasing. We investigated mood status, sleep quality and the health-related quality of life (HRQoL) in these patients. A total of 94 pairs ax-SpA patients and age- and sex-matched healthy controls were included in this cross-sectional study. Demographic and clinical data were collected. We assessed the disease activity by the Ankylosing Spondylitis Disease Activity Score, including C-reactive protein (ASDAS-CRP), the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Bath Ankylosing Spondylitis Functional Index (BASFI). The Hospital Anxiety and Depression Scale (HADS), the Pittsburgh Sleep Quality Index (PSQI) and the Medical Outcomes Survey Sheet Form-36 (SF-36) were used to evaluate mood status and quality of sleep and life, respectively. We evaluated the factors related to anxiety and depression scores, sleep disturbance scores and quality of life scores, and the predictors of anxiety, depression and sleep disturbance were analyzed. Forty-five active patients and forty-nine relieved patients were enrolled. We found that the median HADS anxiety (HADS-A), depression (HADS-D) subscale scores and PSQI score were significantly higher in active ax-SpA than in inactive patients, and were significantly higher than those in controls (HADS-A 9 vs. 5 vs. 3, p < 0.001; HADS-D 8 vs. 5 vs. 3, p < 0.001; PSQI 10 vs. 6 vs. 3, p < 0.001). Moreover, the HADS-A scores were positively correlated to positive HLA-B27 (p = 0.042), pain (p = 0.002) and the BASFI score (p = 0.012), HADS-D scores were positively correlate to disease course (p < 0.001) and PSQI scores were significantly positively correlated to the BASFI score (p = 0.009). Logistic regression analysis showed that BASFI was a risk factor for anxiety, age was a protective factor for depression and disease course was a risk factor for depression. The optimal cut-off value of BASFI in predicting anxiety was 1.55 with an area under the curve value of 0.8488 (p < 0.001), and the optimal cut-off value of age and the course of the disease in predicting depression was 50.5years old with an area under the curve value of 0.62 (p = 0.0482) and 54months with an area under the curve value of 0.7988 (p < 0.001). In addition, disease activity was negatively correlated with SF-36 dimensions, and anxiety, depression and sleep disturbance in ax-SpA patients also had significant negative effects on HRQoL (p < 0.05). Patients with active ax-SpA tend to be more anxious, depressed and sleep disturbed, and have worse HRQoL than patients in remission. Patients with ax-SpA are more likely to be anxious with worse spinal function, more likely to be depressed with younger age and longer course of disease. Therefore, the assessment of mental health, sleep and HRQoL should also be included in the long-term management of patients with ax-SpA. Key Points • Active ax-SpA patients tend to have more anxiety, depression, sleep disturbances and worse HRQoL compared with patients in remission • The optimal cut-off value of BASFI in predicting anxiety was 1.55, the age and the course of the disease in predicting depression was 50.5years old and 54months.

Evaluation of disease course and major complications in juvenile idiopathic inflammatory myopathy patients

Evaluation of disease course and major complications in juvenile idiopathic inflammatory myopathy patients

Differential TLR2 and TLR4 mediated inflammatory and apoptotic responses in asymptomatic and symptomatic Leptospira interrogans infections in canine uterine tissue

Leptospirosis is major zoonotic disease with global implications, affecting both domestic animals and humans. It is caused by Leptospira interrogans (L. interrogans), which can damage multiple organs, including the kidneys, liver, testes, and uterus. Despite this, L. interrogans can also persist asymptomatically in tissues, akin to nonpathogenic strains. The mechanisms driving asymptomatic infections remain poorly understood. This study investigated the role of L. interrogans in asymptomatic infection within the uterine tissue of canines, focusing on the differential expression of Toll-like receptors (TLRs)2 and 4 and their roles in inflammatory and apoptotic pathways. We hypothesized that TLR2 and TLR4 coexpression is crucial for eliciting inflammation and apoptosis, whereas TLR4 alone might be insufficient. Our findings revealed that in symptomatic infections, both TLR2 and TLR4 are coexpressed, leading to markedly elevated levels of the proinflammatory cytokines IL-10, IL-1β, TNF-α, and IL-6. This enhanced inflammatory response is further evidenced by increased CD4 expression, indicating robust T helper cell activation. In contrast, asymptomatic infections are characterized by exclusive TLR4 expression, with inflammatory markers remaining at baseline levels. Additionally, we observed that L. interrogans induces apoptosis in symptomatic animals through TLR2 and TLR4 mediated activation of Caspase 8 and Caspase 3. These findings illustrate that L. interrogans drives both inflammation and apoptosis via the combination of TLR2 and TLR4 actions. When only TLR4 is activated, the immune response is insufficient, resulting in an asymptomatic disease course. This study provides novel insights into the differential roles of TLR receptors in leptospirosis, offering potential directions for targeted therapeutic strategies.

Infective endocarditis in injection drug users: disease course, diagnostic and clinical aspects (clinical case analysis)

Aim. To present and clinically analyze a case of “injection drug users” infective endocarditis (IE) to increase awareness among general practitioners and cardiologists about this special variant of IE.Materials and methods. Clinical observation of a 39-year-old female patient with long-term heroin and methadone addiction, viral hepatitis C, who was diagnosed with acute primary IE caused by methicillin-sensitive Staphylococcus aureus localized on the tricuspid and mitral valves. Bilateral septic pulmonary embolism and respiratory failure, secondary anemia, thrombocytopenia, nephrotic syndrome due to secondary glomerulonephritis were observed. On the 21st day of treatment, the patient underwent tricuspid valve replacement surgery with a biological prosthesis and multicomponent reconstruction of the mitral valve, the postoperative period was complicated by the development of exudative pericarditis.Results. The clinical picture and the course of a complex case of “injection drug users” IE are discussed. The difficulties of early diagnostics of IE caused by the absence of pathognomonic clinical manifestations of the disease and the variability of the debuts of IE with the prevalence of extracardiac manifestations is highlighted. The principles of antibacterial therapy and indications for surgical treatment are reviewed.Conclusion. Clinical observation draws the attention to the high probability of diagnosing IE in cases of fever in intravenous drug users and demonstrates both the difficulties of treatment and the possibility of a favorable outcome of this serious disease with timely diagnosis, appropriate antibacterial therapy, and early cardiac surgery.

Structural alterations as a predictor of depression - a 7-Tesla MRI-based multidimensional approach.

Major depressive disorder (MDD) is a debilitating condition that is associated with changes in the default-mode network (DMN). Commonly reported features include alterations in gray matter volume (GMV), cortical thickness (CoT), and gyrification. A comprehensive examination of these variables using ultra-high field strength MRI and machine learning methods may lead to novel insights into the pathophysiology of depression and help develop a more personalized therapy. Cerebral images were obtained from 41 patients with confirmed MDD and 41 healthy controls, matched for age and gender, using a 7-T-MRI. DMN parcellation followed the Schaefer 600 Atlas. Based on the results of a mixed-model repeated measures analysis, a support vector machine (SVM) calculation followed by leave-one-out cross-validation determined the predictive ability of structural features for the presence of MDD. A consecutive permutation procedure identified which areas contributed to the classification results. Correlating changes in those areas with BDI-II and AMDP scores added an explanatory aspect to this study. CoT did not delineate relevant changes in the mixed model and was excluded from further analysis. The SVM achieved a good prediction accuracy of 0.76 using gyrification data. GMV was not a viable predictor for disease presence, however, it correlated in the left parahippocampal gyrus with disease severity as measured by the BDI-II. Structural data of the DMN may therefore contain the necessary information to predict the presence of MDD. However, there may be inherent challenges with predicting disease course or treatment response due to high GMV variance and the static character of gyrification. Further improvements in data acquisition and analysis may help to overcome these difficulties.

Cognitive Behavioral Therapy in the Treatment of Sleep Disorders: Theoretical Foundations, Research Methods and Analysis of Effectiveness

Sleep disorders are not just a disruption of a person’s normal recovery process and a deterioration in life quality. It has been repeatedly demonstrated that insomnia is an independent factor that worsens the course of somatic diseases and leads to psycho-emotional disorders of varying severity. Research into cognitive behavioural therapy for insomnia aims to provide answers to these questions. The most effective non-pharmacological treatments for insomnia are behavioural and psychotherapeutic methods that improve sleep and do not cause side effects or addiction. The chosen research topic is also relevant in the context of the increasing prevalence of insomnia due to the profound shocks of the Russian-Ukrainian war among internally displaced persons, various other stresses and interpersonal conflicts. All these and many other factors can cause acute insomnia. Patients with insomnia often have increased emotional reactivity, which can also lead to disorders. The findings of the research help understand the psychological factors involved in the processes of researching cognitive behavioural therapy for sleep disorders and can be used by practitioners who are faced with the need to treat patients with insomnia; it will help to understand traumatic experiences and emotional needs better. In conclusion, cognitive behavioural therapy is a practical, non-pharmacological approach to the treatment of sleep disorders, including insomnia. The study highlights the importance of addressing psychological factors, such as emotional reactivity and traumatic experiences, which are often associated with insomnia. As well as providing valuable information for practitioners, this study highlights the importance of individualised therapeutic interventions, particularly in high-stress environments such as those resulting from war and displacement. cuments in various Scopus indexed journals was examined bibliometrically, for the years 2014-2024.