Manifestations Of Disease Research Articles

Fatigue levels and associated factors in systemic sclerosis: a cross-sectional study of 2,385 SPIN Cohort participants.

To compare fatigue in a large multinational systemic sclerosis (SSc) cohort to general population data and identify associated sociodemographic, lifestyle and SSc disease factors. Scleroderma Patient-centered Intervention Network Cohort participants completed the Patient-Reported Outcomes Measurement Information System-29 v2.0 fatigue domain. T-scores were compared with the USA general population (mean = 50; SD = 10). Multivariable linear regression was used to assess associations with sociodemographic, lifestyle, and disease-related variables. Among 2,385 participants (mean age 54.9 (SD = 12.6) years, 87% female, 38% diffuse SSc), mean fatigue T-score was 54.6 (SD = 11.0); 438 (18%) reported mild fatigue, 641 (27%) moderate, and 180 (8%) severe fatigue. Fatigue was independently associated with sociodemographic factors age (-0.10 points per year, [95% CI -0.14;-0.07]), male sex (-1.67 points, [-2.96;-0.37]), non-married status (0.97 points [0.04; 1.89]), and country (reference USA; France -2.35 points [-3.48;-1.21] and UK 2.38 points [0.80; 3.97]), and lifestyle factors smoking (4.16 points [2.52; 5.80]), alcohol consumption (-0.18 points per drink per week [-0.28;-0.07]), and body-mass index (0.34 points per unit [0.27; 0.42]). Fatigue was associated with disease-related factors gastrointestinal involvement (4.21 points [2.99; 5.43]), digital ulcers (1.51 points, [0.25; 2.77]), moderate small joints contractures (1.41 points [0.13; 2.69]), rheumatoid arthritis (4.34 points [2.37-6.31]) and Sjögren's syndrome (1.89 points [0.23; 3.55]). When pain was included in the model, its association was large (2.19 points [2.03; 2.34]) and interstitial lung disease was also associated (1.21 points [0.42; 2.00]). In people with SSc, fatigue scores were substantially higher than the general population and associated with multiple disease factors including gastrointestinal involvement, several painful disease manifestations, and lung involvement.

Expression of TRPS1 in Metastatic Tumors of the Skin: An Immunohistochemical Study of 72 Cases

TRPS1 (Tricho-rhino-phalangeal syndrome 1) is a GATA transcriptional activator gene encoding for a protein used as a sensitive immunohistochemical marker of breast carcinomas. In dermatopathology, TRPS1 is used as a marker of mammary and extramammary Paget’s disease and is also expressed by a variety of primary cutaneous tumors, mostly of adnexal origin. So far, very limited data exist on the expression of TRPS1 in metastatic skin tumors. We studied the immunohistochemical expression of TRPS1 in 72 cutaneous metastatic tumors from the breast (n: 19) and other origins (n: 53) in order to assess its diagnostic usefulness. The intensity of TRPS1 immunostaining was expressed as a histoscore: the product of the percentage of positive cells (scored semi-quantitatively 0–4) and the staining intensity (scored 0–3). In normal skin, nuclear TRPS1 expression was predominantly observed in cells of adnexal structures (pilosebaceous follicles and sweat glands). Eighteen (18/19, 94.7%) metastatic breast carcinomas showed diffuse and strong TRPS1 positivity (histoscore 12). Lower reactivity was found in some other metastases, including from the lung (11/22), the female genital tract (3/4), and the kidney (2/4), whereas most (20/22) metastases from the digestive system and peritoneum, along with a case of metastatic prostate carcinoma, were negative. These results suggest that a high histoscore for TRPS1 is in favor of the mammary origin of metastatic cutaneous carcinoma. Although TRPS1 is not absolutely specific or sensitive to a particular primary, we consider that it can be added to a panel of other markers when investigating the origin of a cutaneous metastasis, namely when this is the first manifestation of the neoplastic disease.

Exploring Dual-Targeted Therapy in the Management of Moderate to Severe Inflammatory Bowel Disease: A Retrospective Study

Abstract Background Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), often results in significant morbidity among patients with moderate to severe forms. While biologics and small molecules are effective in inducing remission, many patients experience refractory disease or extra-intestinal manifestations. This study assesses the safety and efficacy of dual-targeted therapy in IBD patients treated at the Inflammatory Bowel Disease Center. Methods This retrospective cohort study examined 79 patients with UC or CD who received dual-targeted therapy at the University from October 2018 to August 2023. Data collected included demographics, disease characteristics, previous treatments, and clinical outcomes. Primary outcomes were endoscopic, radiographic, and patient-reported clinical improvements, with secondary outcomes focusing on safety profiles. Results Among the 79 patients (42 UC, 37 CD), 97 dual-targeted therapy cases were analyzed, primarily involving a biologic combined with a JAK inhibitor (90.7%). The median therapy duration was 39.1 weeks. Endoscopic improvement occurred in 69% of matched samples, with significant differences between pre- and post-dual-targeted therapy Mayo scores for UC (p = 0.002) and SES-CD scores for CD (p = 0.018). The median pre- and post-dual-targeted therapy Mayo scores across matched samples were 3 (range 1-3) and 1 (range 0-3) respectively, and for SES-CD scores were 12 (range 0-36) and 4 (range 0-20) respectively. Clinical improvement was reported by 73.2% of patients, with notable reductions in ESR (median 19 [range 2-124] mm/hr to 9 [range 0-116] mm/hr, p = 0.006), CRP (median 8.0 [range 0.2-78.5] mg/L to 3.0 [range 0.2-68.2] mg/L, p <0.001) , and albumin levels (4.0 [range 2.2-4.9] mg/dL to 4.2 [range 3.4-5.2], p < 0.001). Non-obesity was associated with both more endoscopic improvement (p = 0.002) and clinical improvement (p = 0.007). Adverse events occurred in 37 cases, predominantly upper respiratory tract infections and dermatologic issues, with no thromboembolic events reported. Discussion Dual-targeted therapy demonstrated efficacy in improving clinical and endoscopic outcomes in patients with severe, refractory IBD, and exhibited an acceptable safety profile. Despite the promising results, further research is needed to confirm these findings and determine optimal therapy combinations.

Characteristics of Inherited Metabolic Disorders Following Kidney Transplantation: A 13-Year Observational Study

Background and Objectives: Inherited metabolic disorders (IMDs), primarily cystinosis, Fabry disease, and methylmalonic acidemia (MMA), are genetic conditions that typically result in multi-organ disease manifestations. Kidney function progressively deteriorates in many cases, with patients eventually reaching end-stage kidney disease (ESKD) and requiring renal replacement therapy. Kidney transplantation has been deemed the optimal renal replacement therapy option to achieve long-term survival in patients with IMD. Whilst improved long-term survival is expected, the patterns of clinical evolution for IMD after transplantation remain largely unknown. Methods: Our group conducted a retrospective observational study that included 37 adult patients with IMD (11 with cystinosis, 20 with Fabry disease, and 6 with MMA). The study evaluated the clinical status and progression of these patients following kidney transplantation between January 2010 and December 2023. Results: This generally resulted in good graft outcomes for patients with IMD. Standard immunosuppression regimes included tacrolimus, mycophenolate mofetil, and prednisolone. The mean graft survival duration was noted to be 12 years in patients with cystinosis, 11 years in patients with Fabry disease, and 7 years in patients with MMA. Suboptimal outcomes were noted with grafts of cadaveric origin and poor adherence to the prescribed post-transplant immunosuppression regime. A greater extra-renal morbidity burden was associated with a reduced duration of graft function and increased mortality in patients with IMD. Conclusions: Our findings emphasise the need for a multi-disciplinary approach in the care of IMD patients following kidney transplantation.

Psoriasis: Sind Geschlechtsunterschiede bedeutsam?

Background: Psoriasis is a common chronic inflammatory skin disease with an exceptionally high burden for women. Objective: Sex-dependent differences in disease manifestation, severity, treatment choices, subjective disease perception, and the impact on quality of life and risk factors are described and comprehensively discussed. Methods: A literature search was conducted using MEDLINE (PubMed) and the Cochrane Library for systematic reviews to investigate the challenges in treating women with psoriasis. Results and conclusions: : The incidence, prevalence, and manifestation of psoriasis of the skin are similar between different sexes. Genetic and environmental factors such as obesity and metabolic syndrome are risk factors and are not equally relevant or pronounced in women and men. Overall, women have a lower disease severity measured by the Psoriasis Area Severity Index, which is associated with a higher impairment of their life quality measured by the Dermatology Life Quality Index compared with men. In addition, women with psoriasis are more likely to have depression than men. Hormonal factors affect psoriasis, with a correlation of high estrogen levels and improvement of psoriasis. Data regarding differences in prescribing patterns of systemic treatments and the severity of psoriasis are not entirely consistent. Registry studies show that men tend to have more severe psoriasis and, in some cases, are prescribed systemic therapies more frequently. Women tend to respond better to systemic treatments and to experience more adverse events. Treatment options are the same for both sexes, except during pregnancy and lactation. Various treatment options are contraindicated due to fear of fetal or neonate harm and lack of data. Topical steroids can be prescribed with a high degree of safety during pregnancy. For other topical therapies (calcineurin inhibitors and vitamin D analogs), no studies of adverse effects in pregnancy are available, and safety data mainly stem from studies examining effects after systemic administration. Antitumor necrosis factor monoclonal antibodies (except for certolizumab pegol) have been associated with a possible increased risk of preterm birth, low gestational age, and cesarean deliveries. Prospective data on the safety of biologics other than antitumor necrosis factor-alpha antibodies to accurately assess whether novel biologics (eg, anti-interleukin 17, 12/23, 23) can be used for systemic therapy in pregnancy are lacking or currently being conducted. © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of Women’s Dermatologic Society.

The presence of oligoclonal bands predicts conversion to multiple sclerosis in isolated myelitis

Acute transverse myelitis (ATM) is a disease characterized by inflammation of the spinal cord and may have various causes. In the context of this work, the distinction between isolated ATM and initial manifestation of autoimmune-mediated diseases of the central nervous system such as multiple sclerosis (MS) is crucial. Hence, the aim of this work was to identify predictive factors associated with the conversion to definite MS in a collective of individuals after their initial episode of isolated ATM (no initial identified cause). In this retrospective data analysis from the Vienna MS Database, all patients from Jan. 1, 1999, to Dec. 31, 2019, with a diagnosis of isolated ATM (according to the criteria of the Transverse Myelitis Consortium Working Group) who underwent lumbar puncture were extracted. Electronic medical records were reviewed on the availability of clinical data including therapy and follow-up, laboratory results including cerebrospinal fluid (CSF) analysis, evoked potentials (EP) as well as magnetic resonance imaging data. Among 42 patients with the diagnosis of isolated ATM, 12 (29%) were subsequently diagnosed with MS over a median follow-up period of 7.7 years. Univariately, MS converters were younger (32 years [25–39] vs. 42 years [31–50], p = 0.032), had a lower CSF/serum albumin ratio (29 [24–35] vs 37 [27–52], p = 0.037), lower CSF total protein (4.5 [2.8–4.8] vs. 5.5 [3.4–8.5], p = 0.023) and a higher proportion of CSF-specific oligoclonal bands (OCB; 83% vs. 30%, p = 0.002). In the multivariate regression analysis, the presence of CSF-specific OCB emerged as the sole predictive factor of subsequent MS diagnosis (OR: 14.42, 95% CI 1.39 to 149.48, p = 0.03). In a collective of 42 patients with isolated ATM and an MS conversion rate of nearly 30%, the only but highly predictive factor were CSF-specific OCB. This emphasizes the significance of conducting timely CSF analysis in such patients and underscores the need for tailored monitoring and follow-up strategies in this specific group.

Complex therapy of musculoskeletal pain: the role of centrally acting muscle relaxants

Chronic pain is the main manifestation of musculoskeletal diseases (MSDs), leading to deterioration of quality of life and loss of ability to work. The importance of this problem is determined by the widespread prevalence of MSDs, osteoarthritis (OA), acute and chronic non-specific back pain (NBP), periarticular soft tissues lesions. Introduction of effective methods of treatment of musculoskeletal pain (MSP) into medical practice is one of the fundamental tasks of modern medicine.The pathogenesis of MSP includes mechanisms such as injury, inflammation, peripheral sensitization, biomechanical disorders, dysfunction of the nociceptive system and psychoemotional disorders. Painful muscle tension plays an important role in the development of MSP, especially in NBP. Given the complex pathogenesis of MSP, its treatment is based on the combined use of drugs with different mechanisms of action and nonpharmacological methods. Non-steroidal anti-inflammatory drugs (NSAIDs) have a central place in this context. However, they can cause serious adverse reactions (ARs), so when choosing NSAIDs, it is necessary to consider comorbid pathology and risk factors. One of the most acceptable NSAIDs with a pronounced analgesic effect and low incidence of ARs is aceclofenac, which is available in various dosage forms (tablets, sachets, topical cream for external use). This medication is characterized by proven efficacy and good tolerability.Centrally acting muscle relaxants (CM) play an important role in the treatment of MSP. They eliminate muscle spasm, enhance the effect of analgesics and reduce the need for NSAIDs. The effect of CM has been demonstrated in spasticity and NBP. However, the use of many drugs of this group can be associated with serious ARs, which limits their use.Tolperisone has the best combination of efficacy and favorable safety profile among CM. Its positive effect in the complex treatment of NBP has been confirmed in several well-organized, placebo-controlled trials. There are also studies demonstrating the efficacy of tolperisone in OA. An important advantage of this drug is virtually no sedative effect, and no negative impact on hemodynamics and on the ability to perform concentration-intensive work. Emergence of a new form of tolperisone – extended-release tablets (Mydocalm® Long 450 mg) – increases patient compliance with CM therapy and facilitates the physician's work.

Celecoxib in rheumatic diseases: possibilities and prospects. Brief descriptive survey

Chronic pain is the main manifestation of rheumatic diseases (RD), it determines the main complaints and worsens the quality of life of patients. The problem of effective control of chronic pain in rheumatology remains a current issue despite the successes in the development of new drugs for pathogenetic therapy, especially in immunoinflammatory RD. For example, 40-50% of patients with rheumatoid arthritis (RA), even those receiving biologic disease-modifying antirheumatic drugs and Janus kinase inhibitors, require analgesics. According to several population studies, about 50% of patients with the most common RD, osteoarthritis (OA) are forced to take various analgesics on a regular basis.The most popular class of analgesics with proven efficacy in RA, spondyloarthritis (SpA) and OA are non-steroidal anti-inflammatory drugs (NSAIDs). As has been shown in several meta-analyses, NSAIDs are superior to placebo and paracetamol in their therapeutic effect, are not inferior to opioids and are better tolerated overall. However, the use of NSAIDs can be associated with the development of dangerous adverse events (AEs), which requires careful monitoring of the patient's condition, considering comorbid diseases and risk factors. It is very important to choose a drug with a balanced ratio of efficacy and low risk of gastrointestinal and cardiovascular AEs. One such drug is celecoxib, whose therapeutic potential and relative safety have been confirmed in RA, SpA and OA. A differentiated approach to celecoxib prescription makes it possible to achieve a maximum therapeutic result with a minimum risk of AEs. For severe pain, treatment starts with a dose of 400 mg/day, followed by a switch to a maintenance dose of 200 mg/day.

Regulatory mechanism of DDX5 in ox-LDL-induced endothelial cell injury through the miR-640/SOX6 axis.

Endothelial dysfunction is an early and pre-clinical manifestation of coronary heart disease (CHD). This study investigates the role of DDX5 in oxidized low-density lipoprotein (ox-LDL)-induced endothelial cell injury to confer novel targets for the treatment of CHD. Endothelial cells were induced by ox-LDL. DDX5, pri-miR-640, pre-miR-640, miR-640, and SOX6 expressions were analyzed by RT-qPCR and Western blot. DDX5 expression was intervened by shRNA, followed by CCK-8 analysis of proliferation, flow cytometry detection of apoptosis, and tube formation assay analysis of angiogenic potential of cells. The binding between DDX5 and pri-miR-640 was determined by RIP, and the pri-miR-640 RNA stability was measured after actinomycin D treatment. Dual-luciferase assay verified the targeting relationship between miR-640 and SOX6. DDX5 and miR-640 were highly expressed while SOX6 was poorly expressed in ox-LDL-induced endothelial cells. Silence of DDX5 augmented cell proliferation, abated apoptosis, and facilitated angiogenesis. Mechanistically, RNA binding protein DDX5 elevated miR-640 expression by weakening the degradation of pri-miR-640, thereby reducing SOX6 expression. Combined experimental results indicated that overexpression of miR-640 or low expression of SOX6 offset the protective effect of DDX5 silencing on cell injury. DDX5 elevates miR-640 expression by repressing the degradation of pri-miR-640 and then reduces SOX6 expression, thus exacerbating ox-LDL-induced endothelial cell injury.

Corticostriatal Maldevelopment in the R6/2 Mouse Model of Juvenile Huntington's Disease.

There is a growing consensus that brain development in Huntington's disease (HD) is abnormal, leading to the idea that HD is not only a neurodegenerative but also a neurodevelopmental disorder. Indeed, structural and functional abnormalities have been observed during brain development in both humans and animal models of HD. However, a concurrent study of cortical and striatal development in a genetic model of HD is still lacking. Here we report significant alterations of corticostriatal development in the R6/2 mouse model of juvenile HD. We examined wildtype (WT) and R6/2 mice at postnatal (P) days 7, 14, and 21. Morphological examination demonstrated early structural and cellular alterations reminiscent of malformations of cortical development, and ex vivo electrophysiological recordings of cortical pyramidal neurons (CPNs) demonstrated significant age- and genotype-dependent changes of intrinsic membrane and synaptic properties. In general, R6/2 CPNs had reduced cell membrane capacitance and increased input resistance (P7 and P14), along with reduced frequency of spontaneous excitatory and inhibitory synaptic events during early development (P7), suggesting delayed cortical maturation. This was confirmed by increased occurrence of GABA A receptor-mediated giant depolarizing potentials at P7. At P14, the rheobase of CPNs was significantly reduced, along with increased excitability. Altered membrane and synaptic properties of R6/2 CPNs recovered progressively, and by P21 they were similar to WT CPNs. In striatal medium-sized spiny neurons (MSNs), a different picture emerged. Intrinsic membrane properties were relatively normal throughout development, except for a transient increase in membrane capacitance at P14. The first alterations in MSNs synaptic activity were observed at P14 and consisted of significant deficits in GABAergic inputs, however, these also were normalized by P21. In contrast, excitatory inputs began to decrease at this age. We conclude that the developing HD brain is capable of compensating for early developmental abnormalities and that cortical alterations precede and are a main contributor of striatal changes. Addressing cortical maldevelopment could help prevent or delay disease manifestations.

Congenital Insensitivity to Pain With Anhidrosis Is Associated With Harlequin Color Change: A Survey Study.

Congenital insensitivity to pain with anhidrosis (CIPA), also known as hereditary sensory and autonomic neuropathy (HSAN) type IV, is an extremely rare autosomal recessive congenital condition characterized by the loss of sensation to pain and absence of sweating with one case report linking this with harlequin color change. To explore the relationship further, we developed a survey using the Research Electronic Data Capture software and distributed it to families and others with close relationships and knowledge of patients with CIPA. Our results indicate that harlequin color change, characterized by unilateral flushing of the face and/or body, was significant and noted by all respondents as being present early in the condition appearing around the same time as first symptoms and around or before diagnosis of CIPA. Future clinicians should be aware of this dermatological phenomenon and its potential association with CIPA patients, especially during early disease manifestation where diagnosis can be difficult.

The future of cystic fibrosis: A global perspective.

The severity of lung disease as well as other disease manifestations have dramatically improved in those patients with cystic fibrosis (CF) that both have mutations responsive to small molecule- based therapies with CF transmembrane regulator (CFTR) modulators and do have access to these drugs. Unfortunately, these medications are not available to many patients with CF across the globe with access largely limited to high income countries. For those eligible to CFTR modulators new questions have arisen regarding the ongoing need for other medications addressing CF lung disease as well current care models with tight monitoring. This article aims to summarize how CF care may change in the future making a plea to expand the availability of highly effective medications to every child with CF that could benefit from treatment.

Regulation of the NLRP3 inflammasome by autophagy and mitophagy.

The NLRP3 inflammasome is a multiprotein complex that upon activation by the innate immune system drives a broad inflammatory response. The primary initial mediators of this response are pro-IL-1β and pro-IL-18, both of which are in an inactive form. Formation and activation of the NLRP3 inflammasome activates caspase-1, which cleaves pro-IL-1β and pro-IL-18 and triggers the formation of gasdermin D pores. Gasdermin D pores allow for the secretion of active IL-1β and IL-18 initiating the organism-wide inflammatory response. The NLRP3 inflammasome response can be beneficial to the host; however, if the NLRP3 inflammasome is inappropriately activated it can lead to significant pathology. While the primary components of the NLRP3 inflammasome are known, the precise details of assembly and activation are less well defined and conflicting. Here, we discuss several of the proposed pathways of activation of the NLRP3 inflammasome. We examine the role of subcellular localization and the reciprocal regulation of the NLRP3 inflammasome by autophagy. We focus on the roles of mitochondria and mitophagy in activating and regulating the NLRP3 inflammasome. Finally, we detail the impact of pathologic NLRP3 responses in the development and manifestations of pulmonary disease.

Sarcoidosis: oral manifestations (case report)

Relevance. Sarcoidosis is a multisystem granulomatous disease of unknown origin, commonly presenting with bilateral hilar lymphadenopathy, pulmonary infiltrates, and involvement of the eyes, skin, gums, and oral mucosa. This clinical case illustrates the oral manifestations of this rare systemic disease. Gingival hypertrophy and soft tissue lesions on the lip mucosa were the initial signs of the condition. Following an extended diagnostic process, the patient underwent treatment by both a dentist and a rheumatologist, leading to a stable remission of the disease.Case description. This article presents a clinical case of sarcoidosis manifesting in the mouth as gingival hypertrophy and a soft tissue lesion on the upper lip. In most cases, a diagnosis of sarcoidosis is made before any oral symptoms appear. Diagnosing a systemic disease based on primary oral symptoms poses a unique challenge, as dental professionals may not always be familiar with the oral manifestations of systemic conditions. In cases of suspected sarcoidosis, the oral mucosa should be thoroughly examined, and systemic sarcoidosis should be considered in the differential diagnosis of granulomatous lesions in the mouth.Conclusion. Early initiation of treatment can significantly improve the patient's quality of life and prognosis.

The role of P-CABs in GERD.

Potassium-competitive acid blockers (P-CABs) constitute a relatively new class of gastric acid-suppressing drugs. Among this class, vonoprazan is the first to have been approved in the United States. However, some P-CABs including vonoprazan, tegoprazan and fexuprazan have been available in other countries since at least 2014. The first aim of this article is to review pharmacological differences between P-CABs that are currently approved or in development with proton pump inhibitors (PPIs). The specific focus thereafter is on the likely role of P-CABs in the treatment of different manifestations of gastroesophageal reflux disease (GERD). Multiple clinical trials have compared P-CABs with PPIs in erosive esophagitis. Additional trials have compared P-CABs with placebo in non-erosive reflux disease. Relevant results are reviewed and inferences drawn for their use in the US. Lastly, consideration is given to additional, potential uses of P-CABs in the broader spectrum of GERD and some suggestions made for future research initiatives.

Comorbidity of inflammatory bowel diseases and periodontal pathology

Inflammatory bowel diseases, which include Crohn’s disease and ulcerative colitis, are a global disease of the 21st century. Periodontitis is the sixth most common disease in the world (second among dental pathologies after caries) and the leading cause of tooth loss in adults. At the beginning of the 21st century, the concept of “periodontal medicine” was formed, within the framework of which the bidirectional connection of periodontal pathology with systemic diseases of the body is considered. Extraintestinal manifestations of inflammatory bowel disease are associated with the generalized nature of the inflammatory response. In clinical guidelines, only aphthous stomatitis is described as a systemic manifestation of Crohn’s disease and ulcerative colitis from the oral cavity. Periodontitis is considered a less representative non-specific oral manifestation of inflammatory bowel disease. We searched the Pubmed and Scopus information databases for articles published before 02/15/2024 that examined the relationship between inflammatory bowel disease and periodontal pathology. The results of clinical studies, their synthesis in systematic reviews and meta-analyses, indicate a bidirectional relationship between Crohn’s disease and ulcerative colitis with periodontal pathology. The most likely mechanism is associated with a change in the microbiocenosis of the oral cavity and a further change in the intestinal microbiome due to oral intake of periodontal organisms, which leads to impaired intestinal permeability and the development of immune reactions that play a key role in the development of periodontal diseases and inflammatory bowel diseases.

Central retinal artery occlusion as the initial manifestation of mixed connective tissue disease in a young woman: a case report

BackgroundRetinal artery occlusions are rare amongst young adults, and relevant risk factors and etiology remain unclear. In this report, we present a case of central retinal artery occlusion (CRAO) as the initial manifestation of mixed connective tissue disease (MCTD) in a young woman.Case presentationA 22-year-old female presented to the emergency department with a sudden decrease in visual acuity in her right eye for 1 hour. She reported a similar episode in her left eye five years prior, which resolved spontaneously after 2 hours. Initially misdiagnosed with optic neuritis in the right eye at another hospital, she was referred to our institution the following day. Clinical examination revealed a CRAO in her right eye. A detailed medical history revealed that she had developed livedo reticularis (LR) on both lower limbs five years ago, which had been overlooked and untreated. Further rheumatologic history, hematologic tests, and an autoimmune work-up confirmed a diagnosis of mixed connective tissue disease (MCTD).ConclusionIn young patients presenting with CRAO, further examinations should be conducted to investigate systemic disease or an embolic source to prevent future sequelae.

Clinical manifestations of gastroesophageal reflux disease in medical university students

Clinical manifestations of gastroesophageal reflux disease in medical university students

Lipid droplet-associated proteins in alcohol-associated fatty liver disease: A proteomic approach.

The earliest manifestation of alcohol-associated liver disease (ALD) is steatosis characterized by deposition of fat in specialized organelles called lipid droplets (LDs). While alcohol administration causes a rise in LD numbers in the hepatocytes, little is known regarding their characteristics that allow their accumulation and size to increase. The aim of the present study is to gain insights into underlying pathophysiological mechanisms by investigating the ethanol-induced changes in hepatic LD proteome as a function of LD size. Adult male Wistar rats (180-200 g BW) were fed with ethanol liquid diet for 6 weeks. At sacrifice, large-, medium-, and small-sized hepatic LD subpopulations (LD1, LD2, and LD3, respectively) were isolated and subjected to morphological and proteomic analyses. Morphological analysis of LD1-LD3 fractions of ethanol-fed rats clearly demonstrated that LD1 contained larger LDs compared with LD2 and LD3 fractions. Our preliminary results from principal component analysis showed that the proteome of different-sized hepatic LD fractions was distinctly different. Proteomic data analysis identified over 2000 proteins in each LD fraction with significant alterations in protein abundance among the three LD fractions. Among the altered proteins, several were related to fat metabolism, including synthesis, incorporation of fatty acid, and lipolysis. Ingenuity pathway analysis revealed increased fatty acid synthesis, fatty acid incorporation, LD fusion, and reduced lipolysis in LD1 compared to LD3. Overall, the proteomic findings indicate that the increased level of protein that facilitates fusion of LDs combined with an increased association of negative regulators of lipolysis dictates the generation of large-sized LDs during the development of alcohol-associated hepatic steatosis. Several significantly altered proteins were identified in different-sized LDs isolated from livers of ethanol-fed rats. Ethanol-induced increases in specific proteins that hinder LD lipid metabolism led to the accumulation and persistence of large-sized LDs in the liver.

Association of enthesitis with severity of psoriasis in psoriatic arthritis: an observational study.

The relationship between dermatological and articular manifestations of psoriatic disease remains incompletely elucidated. There is no strong correlation between the severity of cutaneous psoriasis and the clinical phenotypes of psoriatic arthritis (PsA). This study aims to examine the correlation between the severity of psoriasis and various clinical features, including measures of severity and activity of PsA, in a real-world clinical setting. Seventy-six consecutive adult patients of both genders with confirmed diagnoses of psoriatic arthritis (PsA) and psoriasis were included in the study. The Psoriasis Area and Severity Index (PASI) was assessed alongside various PsA variables: tender joint count (TJC), swollen joint count (SJC), duration of morning stiffness, presence of dactylitis and number of affected digits, presence of enthesitis and Maastricht Ankylosing Spondylitis Enthesitis Score (MASES), patient's global assessment (PGA), and examiner's global assessment (EGA). Associations were analyzed using the Spearman correlation test and the Kruskal-Wallis test. Statistical significance was established at p = 0.05. Forty-two men and thirty-four women, median age of 56 (range 33-85) years, participated in the study. The median duration of psoriasis was 216 (range 0-600) months and median duration of PsA was 120 (range 7-456) months. There was no significant correlation between PASI and any PsA variables, except for the correlation between PASI and the presence of enthesitis (ρ = 0.285; p = 0.013). Moreover, older patients and patients with a long history of psoriasis manifested more often with enthesis as a sign of PsA. Our findings emphasize the correlation between the severity of psoriasis and presence of enthesitis in patients with PsA.