Distinct Clinical Syndrome Research Articles

SOX17 - Associated Pulmonary Hypertension in Children: A Distinct Developmental and Clinical Syndrome

ObjectiveTo characterize clinical, hemodynamic, imaging, and pathologic findings in children with pulmonary arterial hypertension (PAH) and variants in SOX17, a novel risk gene linked to heritable and congenital heart disease-associated PAH. Study designWe assembled a multi-institutional cohort of children with PAH and SOX17 variants enrolled in the Pediatric Pulmonary Hypertension Network (PPHNet) and other registries. Subjects were identified through exome and PAH gene panel sequencing. Data were collected from registries and retrospective chart review. ResultsWe identified 13 children (8 female, 5 male) aged 1.6 to 16 years at diagnosis with SOX17 variants and PAH. Seven patients had atrial septal defects (ASD) and two had patent ductus arteriosus. At diagnostic cardiac catheterization, patients had severely elevated mean pulmonary artery pressure (mean 78, range 47-124 mmHg) and markedly elevated indexed pulmonary vascular resistance (mean 25.9, range 4.9-55 WU*m2). No patients responded to acute vasodilator testing. Catheter and CT angiography imaging demonstrated atypical pulmonary artery anatomy including severely dilated main pulmonary arteries, lack of tapering in third and fourth order pulmonary arteries, tortuous ‘corkscrewing’ pulmonary arteries, and abnormal capillary ‘blush.’ Several children had pulmonary artery stenoses and two had systemic arterial abnormalities. Histologic examination of explanted lungs from three patients disclosed plexiform arteriopathy and extensive aneurysmal dilation of alveolar septal capillaries. ConclusionsSOX17-associated PAH is a distinctive genetic syndrome characterized by early onset severe PAH, extensive pulmonary vascular abnormalities, and high prevalence of congenital heart disease with intracardiac and interarterial shunts, suggesting a role for SOX17 in pulmonary vascular development.

Microduplications of ARID1A and ARID1B cause a novel clinical and epigenetic distinct BAFopathy

BackgroundARID1A/ARID1B haploinsufficiency leads to Coffin-Siris syndrome, duplications of ARID1A lead to a distinct clinical syndrome, whilst ARID1B duplications have not yet been linked to a phenotype. MethodsWe collected patients with duplications encompassing ARID1A and ARID1B duplications. Results16 ARID1A and 13 ARID1B duplication cases were included with duplication sizes ranging from 0.1-1.2 Mb(1-44 genes) for ARID1A and 0.9-10.3 Mb(2-101 genes) for ARID1B. Both groups shared features, with ARID1A patients having more severe intellectual disability, growth delay and congenital anomalies. DNA methylation analysis showed that ARID1A patients had a specific methylation pattern in blood, which differed from controls and from patients with ARID1A or ARID1B loss-of-function variants. ARID1B patients appeared to have a distinct methylation pattern, similar to ARID1A duplication patients, but further research is needed to validate these results. Five cases with duplications including ARID1A or ARID1B initially annotated as duplications of uncertain significance were evaluated using PhenoScore and DNA methylation re-analysis, resulting in the reclassification of two ARID1A and two ARID1B duplications as pathogenic. ConclusionOur findings reveal that ARID1B duplications manifest a clinical phenotype and ARID1A duplications have a distinct episignature that overlaps with that of ARID1B duplications, providing further evidence for a distinct and emerging BAFopathy caused by whole gene duplication rather than haploinsufficiency.

Use of sodium oxybate for the treatment of alcohol withdrawal syndrome in patients with acute alcohol-associated hepatitis: A 4-patient case report.

During the treatment of alcohol use disorder, alcohol withdrawal syndrome (AWS) can occur. Benzodiazepines remain the "gold standard" for the pharmacological treatment of AWS. However, other drugs have been approved in some European Countries for the treatment of AWS: namely, clomethiazole in Spain and Germany and sodium oxybate in Italy and Austria. Acute alcohol-associated hepatitis (AAH) is a distinct clinical syndrome characterized by the recent onset of jaundice with or without other signs of liver decompensation in patients with ongoing alcohol consumption. We report 4 paradigmatic clinical cases to analyze the efficacy, safety, and tolerability of the very short half-life (30-45 minutes) sodium oxybate (SO) in the management of AWS with moderate to severe AAH. Compared to SO, "as needed" short-acting benzodiazepines, currently prescribed to treat AWS in patients with AAH, have a much longer half-life (5-25 hours) which increases the risk of drug accumulation. The very short half-life of SO provides a fixed dose approach allowing for a more effective control of AWS than "as needed" therapy throughout the 24 hours. Patients reported anxiety, agitation, diffuse abdominal pain, loss of appetite, and nausea with elevation in serum bilirubin and 2 of them had abdomen distension due to ascites. Patients were affected by moderate or severe AWS and moderate or severe AAH on alcohol-related liver cirrhosis. In order to suppress AWS, all patients were treated with oral sodium oxybate at a dose of 25 mg/kg/day, progressively increased to 50 to 100 mg/kg/day, divided into 3 to 5 administrations. SO was efficient, safe and tolerable in suppressing AWS even in patients with severe AAH. All treated patients showed a rapid improvement of all symptom (via the Clinical Institute of Withdrawal Assessment for Alcohol Scale) and liver test scores (Model for End-Stage Liver Disease). Because of its short half-life, SO can be considered a safe and effective pharmacological option for the AWS in patients with moderate to severe AAH even in comparison to short-acting benzodiazepines, thus avoiding the risk of accumulation. Notably, SO guarantees a fixed approach to cover the possible onset of AWS throughout the 24 hours.

Updates on the Natural History and Clinical Characteristics of NSAID-ERD

Nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (NSAID-ERD) is a distinct clinical syndrome characterized by nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity, asthma, and nasal polyposis. Its diagnosis is challenging owing to variable presentations and a lack of simple tests, leading to diagnostic delays. Recent research has revealed its genetic predispositions, environmental triggers, and associations with atopy and second-hand tobacco smoke exposure or smoking cessation. Despite its severity, diagnostic awareness remains low, leading to the delay in effective management. Therapeutically, NSAID-ERD necessitates multidisciplinary approaches, often combining surgical interventions with medical management, including aspirin desensitization and biologic agents. However, predictive biomarkers for treatment response remain elusive. Understanding the underlying mechanisms driving NSAID-ERD pathogenesis and identifying reliable biomarkers are crucial for enhancing diagnostic accuracy and refining targeted therapeutic strategies for this debilitating condition. This review aims to provide a thorough understanding of NSAID-ERD, covering its history, clinical features, epidemiology, diagnosis, systemic and molecular biomarkers, available treatment options, and avenues for future research.

Ruptured Cerebral Abscess Presenting as Catatonia: A Case Report

Catatonia is a complex syndrome having both neurological and psychiatric manifestations. It has a long history of connection with psychiatric illnesses. Despite being a distinctive clinical syndrome, catatonia often goes unrecognized in both psychiatry and neurology clinics. In the following case report, we demonstrate a case of a massive ruptured brain abscess, presenting primarily as catatonia.

Septic Arthritis of the Spinal Facet Joint: Review of 117 Cases.

Septic arthritis of the spinal facet joints is increasingly recognized in the era of magnetic resonance imaging, but its epidemiology, clinical features, management, and prognosis are ill-defined. We review 101 previously published cases and report 16 cases occurring at our institutions between 2006 and 2018. Most patients presented with fever (60%) and back or neck pain (86%). Radiation into the hip, buttock, or limb was present in 34%. The lumbosacral vertebral segments were involved in 78% of cases. Most cases (64%) were due to Staphylococcus aureus. Bacteremia was present in 66% and paraspinal muscle abscesses in 54%. While epidural abscesses were present in 56%, neurologic complications were seen in only 9%, likely because most abscesses arose below the conus medullaris. Neurologic complications were more common with cervical or thoracic involvement than lumbosacral (32% vs 2%, P < .0001). Extraspinal infection, such as endocarditis, was identified in only 22% of cases. An overall 98% of patients survived, with only 5% having neurologic sequelae. Septic arthritis of the facet joint is a distinct clinical syndrome typically involving the lumbar spine and is frequently associated with bacteremia, posterior epidural abscesses, and paraspinal pyomyositis. Neurologic outcomes are usually good with medical management alone.

Kikuchi disease in acute leukaemia: a distinct clinical syndrome with HLA association.

To report the clinicopathological features of Kikuchi disease in patients with acute leukaemia, emphasising similarities among cases. In a cohort of 454 Kikuchi disease patients, we identified three cases of concurrent acute leukaemia. These patients shared similar clinical traits, with Kikuchi disease emerging approximately a month after induction chemotherapy onset, featuring neck-region lymphadenopathy. Notably, two patients were middle-aged, deviating from the typical age distribution of Kikuchi disease. Histologically, these cases aligned with typical Kikuchi disease. Negative immunohistochemical stains (CD34, CD117, ERG, TdT) indicated the absence of extramedullary leukaemic infiltration. Herpes simplex virus immunohistochemical staining was also negative. Significantly, a human leucocyte antigen (HLA) association was observed in these three cases. HLA-B*15:01, C*04:01, and DRB1*04:06 were more prevalent in these patients compared to the general population (compared with three independent control cohorts: Taiwanese Han Chinese (n = 504), Tzu Chi Taiwanese bone marrow donors (n = 364) and Hong Kong Chinese (n = 5266)). Our study underscores the unique link between Kikuchi disease and acute leukaemia, characterised by specific features and HLA associations. This underlines Kikuchi disease as a possible differential diagnosis in pertinent clinical scenarios. Furthermore, this syndrome offers insights into postchemotherapy immunology in acute leukaemia, enhancing comprehension.

Management of Herpes Zoster solely employing Ayurveda: A case report

Background: Varicella-zoster virus (VZV) causes two distinct clinical syndromes: varicella (chickenpox) and herpes zoster. Though human-specific, varicella-zoster virus infections can last for a few hours or even a day or two outside of humans. Herpes zoster is similar to Visarpa disease in Ayurvedic texts. Visarpa spreads very rapidly to many different body parts. Because it spreads throughout the body, it is also known as Parisarpa. Analysing the herpes zoster symptoms, it reveals vitiating Twak, Rakta, and Mamsa Dhatu, with vitiation of Vata-Pitta-dominated Tridosha. This helps us understand the gravity and importance of the disease. Visarpa is not a chronic illness like Kushtha (skin diseases), but, if left untreated, might lead to severe complications. Material and methods: A 25-year-old female with the main complaint of gradually erupted vesicles on the ventral aspect of her right forearm and excruciating burning pain, erythema, and mild itching. The patient was treated with Patolakaturohinyadi Kashayam, powders of Sariwa (Hemidesmus indicus R.Br.), Yashtimadhu (Glycyrrhiza glabra Linn.), Amalaki (Emblica officinalis Gaertn.), Gandhaka rasayana. Shatadhauta ghrita and Durva ghrita were used for local application. Observation and Result: With the aid of internal treatment employing these yogas, the patient shown optimistic outcomes, and herpes zoster was successfully treated with Ayurveda.

Plasma arginine levels in arginase deficiency in the “real world”

BackgroundDeficiency of arginase-1, the final enzyme in the urea cycle, causes a distinct clinical syndrome and is characterized biochemically by a high level of plasma arginine. While conventional therapy for urea cycle disorders can lower these levels to some extent, it does not normalize them. Until now, research on plasma arginine levels in this disorder has primarily relied on data from specialized tertiary centers, which limits the ability to assess the natural history and treatment efficacy of arginase-1 deficiency due to the small number of patients in each center and technical variations in plasma arginine measurements among different laboratories. MethodIn this study, we reported plasma arginine levels from 51 patients with arginase-1 deficiency in the database of Quest Diagnostics. The samples were collected from different US regions. ResultsThe mean plasma arginine level in these treated patients was 373 μmol/L and the median level was 368.4 μmol/L. Our data set from 30 arginase deficiency patients with plasma amino acid data from five or more collections revealed significant correlations between the levels of arginine and five other amino acids (citrulline, alanine, ornithine, glutamine, and asparagine). ConclusionDespite treatment, the arginine levels remained persistently elevated and did not change significantly with age, suggesting the current treatment regimen is inadequate to control arginine levels and underscoring the need to seek more effective treatments for this disorder.

Is Sexual Aversion a Distinct Disorder or a Trans-Diagnostic Symptom across Sexual Dysfunctions? A Latent Class Analysis

Sexual aversion disorder (SAD) is a chronic condition that impacts sexual and psychological well-being. However, the relevance of SAD as a discrete disorder remains highly debated. This study aimed to clarify the status of SAD as either a distinct disorder or a trans-diagnostic symptom shared among sexual dysfunctions. This cross-sectional study used a latent class analysis approach among a Canadian community sample (n = 1,363) to identify how patterns of SAD symptoms (i.e., sexual fear, disgust, and avoidance) emerge across different spheres of sexual functioning (i.e., desire and arousal, erection or lubrication, genito-pelvic pain, and orgasm) and examine sociodemographic and psychosexual correlates of the identified classes. Examination of fit indices suggested four classes: Sexually functional, Impaired desire and responsiveness, Sexual aversion, and Comorbid sexual dysfunctions. Sexual aversion class members were more likely to be single, had experienced sexual assault in adulthood, and report lower levels of sexual satisfaction and psychological well-being, compared to Sexually functional class members. Results suggest that SAD is a distinct clinical syndrome, while its symptoms may co-occur with other sexual dysfunctions. To ensure that the needs of people with SAD are met with tailored treatment options, future nosography might consider reclassifying SAD as a specific disorder.

Correlates of estimated lifetime cruciate ligament survival inform potential rupture risk reduction strategies: findings from the Exceptional Aging in Rottweilers Study

Cranial cruciate ligament (CCL) rupture is one of the most commonly diagnosed orthopedic conditions of pet dogs, making estimated lifetime cruciate ligament survival an attractive endpoint for studies attempting to define clinical and genetic correlates of rupture risk reduction. Early life experiences contribute significantly to the origins of adult health outcomes, yet our current understanding of modifiable susceptibility factors that drive the high frequency of CCL rupture remains limited. We reasoned that combining lifetime medical history with standardized late-life assessment of lifetime cruciate ligament survival and detailed phenotyping of each dog for selected risk variables would provide a sensitive approach to identify factors that would differentiate between lifelong avoidance versus susceptibility to ligament rupture. Here, we report results of Kaplan–Meier analysis of estimated lifetime cruciate ligament survival and Cox proportional hazards modeling to assess risk variables in a lifetime cohort study of 123 purebred Rottweilers, a breed at high risk for veterinarian-diagnosed CCL rupture. We show that gonad removal during the 24-month developmental period is adversely associated with three measures of susceptibility—increased incidence of CCL rupture, multiplicity (bilateral rupture), and accelerated time to initial CCL failure. Our analysis reveals two other phenotypes—short adult height and the production of offspring (in females)—are associated with significant CCL rupture risk reduction. Together, the results provide clues to an early endocrine influence on lifetime cruciate ligament survival. Further, we identify two distinct clinical syndromes of CCL failure, providing a disease subtyping framework to advance future progress in genetic epidemiology, pathogenesis, and prediction. By conducting an evaluation of estimated lifetime CCL survival in dogs, we show that cruciate ligament survival may be jeopardized by gonad removal during the developmental period. Avoidance of such early environmental adversity may represent an actionable method for the control of canine CCL disease in certain breeds.

Post-thrombotic syndrome and chronic thromboembolic pulmonary hypertension: diagnosis and management.

Post-thrombotic syndrome and chronic thromboembolic pulmonary hypertension are two distinct clinical syndromes associated with adverse patient outcomes following a venous thromboembolism. Clinical manifestations of post-thrombotic syndrome include persistent pain, swelling and ultimately venous ulceration following a deep venous thrombosis. Patients experiencing chronic thromboembolic pulmonary hypertension may have symptoms ranging from exertional dyspnoea to overt right heart failure. From a physician's perspective, the most effective preventative strategy is good quality anticoagulation for prophylaxis of primary and secondary venous thromboembolism. The treatment of post-thrombotic syndrome mainly involves lifestyle modifications alongside the use of elastic compression stockings while patients with chronic thromboembolic pulmonary hypertension should be offered targeted surgical and medical treatment options available at expert centres. Further research is warranted for both conditions to determine the role of direct oral anticoagulants when used with a preventive or therapeutic intent.

An Update on Schistosomiasis

Human schistosomiasis is caused by trematode parasites of the genus Schistosoma. Four species and two distinct clinical syndromes are relevant to humans, including S. haematobium, which is associated with urogenital schistosomiasis, whereas S. mansoni, S. mekongi, and S. japonicum are responsible for intestinal schistosomiasis. These flukes reside in the venous plexus of the human bladder and in mesenteric veins and release eggs that, when trapped in tissues, cause inflammation and fibrosis. More specifically, S. mansoni, S. mekongi, and S. japonicum can cause intestinal inflammation, hepatosplenic periportal fibrosis, portal hypertension, and esophageal varices that can bleed and cause death. In contrast, S. haematobium, a recognized carcinogenic organism, can drive bladder carcinoma and contribute to infertility and cervical cancer. Additionally, schistosomiasis can cause general anaemia, stunted growth, and cognitive impairment.Despite the chronic complications associated with schistosomiasis, public awareness in areas of non-endemicity is limited, and travelers rarely consider risk of infection. We describe the diagnostics available in areas of endemicity, as well as in reference laboratories, to diagnose schistosomiasis in returning travelers or migrants to resource-rich locations.

FLAIR-hyperintense lesions in anti-MOG-associated Encephalitis with Seizures (FLAMES) mimicking new daily persistent headache. Updating the diagnostic paradigm with recommendations for timely diagnosis and management. (P13-5.024)

<h3>Objective:</h3> We present a case report of a patient with abrupt right fronto-temporal headache and neck pain that persisted for 13 days, followed by first-time generalized tonic-clonic seizures, weakness, neglect, and encephalopathy. She was ultimately diagnosed with FLAIR-hyperintense lesions in anti-MOG-associated Encephalitis with Seizures (FLAMES), which resolved with IV methylprednisolone. <h3>Background:</h3> FLAIR-hyperintense lesions in anti-MOG-associated Encephalitis with Seizures <b>(</b>FLAMES) was first described in 2017 as a distinct clinical and radiological syndrome from other anti-MOG-associated syndromes. MOG is a protein on the surface of oligodendrocytes. It helps to modulate myelin immune interactions, and its location on the outermost part of the myelin sheath serves as an immunogenic agent. Main presenting symptoms are seizures (85%) and headaches (70%). <h3>Design/Methods:</h3> History, physical exam, review of literature <h3>Results:</h3> We discuss a case of a 25-year-old previously healthy Asian woman, not on home medications, who experienced abrupt onset of right fronto-temporal headache and neck pain, which persisted for 13 days. She saw her primary care doctor four days prior to admission who recommended continuing ibuprofen. Brain imaging was not obtained at that time. She subsequently developed generalized tonic-clonic seizures with acute left sided weakness, neglect, and encephalopathy, which prompted presentation to the hospital. Video EEG showed right sided lateralized rhythmic delta activity (LRDA), as well as diffuse slowing. Lumbar puncture was performed: OP of 22 mm H20, W108 (35% PMNs, 55% lymphocyte), R 20, P 63.4, G 58.7, CSF culture was negative. CSF MOG antibody was positive at 1:100 and serum MOG antibody was positive at 1:320. Antivirals and antibiotics were stopped when infectious workup returned negative, and she began a five-day course of IV methylprednisolone with dramatic improvement. <h3>Conclusions:</h3> FLAIR-hyperintense lesions in anti-MOG-associated Encephalitis with Seizures (FLAMES) should be included in the differential diagnosis of new, sudden-onset, severe, and persistent headache. Recommendations include early imaging and treatment with corticosteroids. <b>Disclosure:</b> Dr. Michaelson has nothing to disclose. Dr. Langan has nothing to disclose. Dr. Kaunzner has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Kaunzner has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Medlearning.

PD33-04 DEVELOPMENT AND VALIDATION OF A SELF-REPORTED MEASURE FOR UNDERACTIVE BLADDER

You have accessJournal of UrologyCME1 Apr 2023PD33-04 DEVELOPMENT AND VALIDATION OF A SELF-REPORTED MEASURE FOR UNDERACTIVE BLADDER Elodi Dielubanza, Rebekah Zincavage, Michael Maurao, James Ambrosoli, Tamera Bavendam, and Michael O'leary Elodi DielubanzaElodi Dielubanza More articles by this author , Rebekah ZincavageRebekah Zincavage More articles by this author , Michael MauraoMichael Maurao More articles by this author , James AmbrosoliJames Ambrosoli More articles by this author , Tamera BavendamTamera Bavendam More articles by this author , and Michael O'learyMichael O'leary More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003326.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Underactive bladder (UAB) is commonly encountered but poorly defined. Though detrusor underactivity (DU) is the accepted underlying mechanism of UAB, a distinct clinical syndrome has not been described. As such, there is a delay in identifying affected individuals and effective treatments are limited. Validated self-reported symptom measures are invaluable tools for uniform and reproducible symptom assessment and are needed to better characterize this condition, efficiently identify patients, and enable innovation in treatment modalities. We describe the development and validation of a self-reported measure for UAB. METHODS: Following federal guidelines for Patient Reported Outcome Measures (PROM) development and validation, we implemented a 5-stage study design, including sequential qualitative and quantitative assessments. RESULTS: Using existing UAB literature and clinician expert opinion we developed a conceptual model for the study, consisting of five domains including symptoms (e.g. storage, voiding, post-voiding) and impacts (e.g. activities of daily life, burden, quality of life). Phase I focused on concept elicitation and symptom identification through the use of qualitative focus groups and phone interviews. Data collected during the focus groups informed the development of the concept elicitation interview guide. Patients with urodynamic DU were identified and concept elicitation interviews were performed to identify condition specific symptoms, determine the language used by individuals to describe their symptoms and to assess symptom prevalence. Using this data, we created a draft self-administered multidimensional risk assessment questionnaire, containing 34 questions. A separate sample of patients with and without DU were utilized to perform cognitive debriefing of the instrument to assess comprehension, face validity and content validity. A revised questionnaire was created and subjected to psychometric validation with a 3rd cohort of both urological patients and healthy controls. A quantitative scoring algorithm was also developed. CONCLUSIONS: The final instrument is a 14 item self-reported measure focused on symptoms and quality of life, designed to be consistent with Lower Urinary Tract Dysfunction Research Network Comprehensive Assessment of Self Reported Urinary Symptoms. It is designed to be completed in 5-10 minutes. Most questions are on a 5 point rating scale with a recall period of one week. Source of Funding: NIH Grant: 1U01DK110377 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e914 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Elodi Dielubanza More articles by this author Rebekah Zincavage More articles by this author Michael Maurao More articles by this author James Ambrosoli More articles by this author Tamera Bavendam More articles by this author Michael O'leary More articles by this author Expand All Advertisement PDF downloadLoading ...

Phosphomannomutase 2 (PMM2) variants leading to hyperinsulinism-polycystic kidney disease are associated with early-onset inflammatory bowel disease and gastric antral foveolar hyperplasia

Phosphomannomutase 2 (PMM2) deficiency causes Congenital Disorder of Glycosylation (PMM2-CDG), but does not have a recognised association with Inflammatory Bowel Disease (IBD). A distinct clinical syndrome of hyperinsulinism and autosomal recessive polycystic kidney disease (HIPKD) arises in the context of a specific variant in the PMM2 promotor, either in homozygosity, or compound heterozygous with a deleterious PMM2 variant. Here, we describe the development of IBD in three patients with PMM2-HIPKD, with onset of IBD at 0, 6, and 10 years of age. In each case, intestinal inflammation coincided with the unusual finding of gastric antral foveolar hyperplasia. IBD disease was of variable severity at onset but well controlled with conventional and first-line biologic treatment approaches. The organ-level pattern of disease manifestations in PMM2-HIPKD-IBD may reflect a loss of cis-acting regulatory control by hepatocyte nuclear factor 4 alpha (HNF4A). Analysis of published transcriptomic data suggests that IBD most likely arises due to an impact on epithelial cellular function. We identify a specific pattern of variation in PMM2 as a novel association of early-onset IBD with distinctive gastric pathology.

Rheumatoid Myositis: A Rare Case Report

Rheumatoid Arthritis (RA) and inflammatory myositis are distinct clinical syndromes. Muscle involvement in RA is frequently secondary to therapy with steroids or immune-modulators medication. However, the association of myositis in a treatmentnaive patient with RA is rare. Myositis represents a distinct entity with specific clinical, biological, imaging, and histological patterns. Here, authors describe a case of RA presented with myositis. A 30-year-old female presented with insidious onset gradually progressive to paraparesis lasting for six months. This was preceded by a history of inflammatory arthritis involving small and large joints of the upper and lower extremities. Clinically, she exhibited pure motor weakness of the upper and lower limbs (proximal &gt; distal) with hand, elbow, and knee deformities. Her Anti-Cyclic Citrullinated Peptide antibody (Anti-CCP) and inflammatory markers were elevated. Muscle-specific enzymes were also elevated, along with positive myositis-specific antibodies. Electromyography (EMG) and Magnetic Resonance Imaging (MRI) of the thigh revealed findings consistent with inflammatory myositis. The patient was managed as a case of Rheumatoid Myositis (RM) with steroids, conventional, and biological immune-modulators Disease-Modifying Antirheumatic Drugs (DMARDs). She experienced remarkable improvement in her symptoms and quality of life.

Immune Thrombocytopenia (Itp) In Emergency Medicine

Immune Thrombocytopenia (ITP) is an autoimmune disorder characterised by a low platelet countless than 100? ×? 10^9/L, purpura, and hemorrhagic episodes induced by antiplatelet autoantibodies without anemia or leukopenia. Immune thrombocytopenia (ITP) occurs in 2 to 4/100? 000 adults. A wide range of signs and symptoms, from modest mucocutaneous petechiae to severe, life-threatening organ haemorrhage, are seen in ITP patients. they may present to the emergency department (ED) with life-threatening bleeding as a result of their thrombocytopenia. ITP has two distinct clinical syndromes, manifesting as an acute condition in children and a chronic condition in adults. IgG autoantibodies make circulating platelets more sensitive. It causes these cells to be removed more quickly by antigen-presenting cells (macrophages) of the spleen, and occasionally the liver or other components of the monocyte-macrophage system. Current evidence supports alternatives to splenectomy for second-line management of patients with persistently low platelet counts and bleeding. By increasing platelet production, bone marrow compensates for platelet breakdown. Immune Thrombocytopenia most commonly arises within a few weeks after a viral infection in healthy children and young adults. Immunosuppressive treatment is usually effective in treating ITP. Many patients with ITP require no emergent treatment. However, the emergency physician should start treatment with a platelet transfusion, corticosteroids, and intravenous immune globulin (IVIG) as soon as the patient with suspected ITP arrives at the ED with serious haemorrhage.The diagnosis is usually made by ruling out all known causes of thrombocytopenia. This review aims to summarize current evidences regarding prevalence, causes, diagnosis and management of immune thrombocytopenia. Keywords:,,,

Mesenchymal stem cells exosomal let-7a-5p improve autophagic flux and alleviate liver injury in acute-on-chronic liver failure by promoting nuclear expression of TFEB

Acute-on-chronic liver failure is a distinct clinical syndrome characterized by a dysregulated immune response and extensive hepatocyte death without satisfactory therapies. As a cytoplasmic degradative and quality-control process, autophagy was implicated in maintaining intracellular homeostasis, and decreased hepatic autophagy was found in many liver diseases and contributes to disease pathogenesis. Previously, we identified the therapeutic potential of mesenchymal stem cells (MSCs) in ACLF patients; however, the intrinsic mechanisms are incompletely understood. Herein, we showed that MSCs restored the impaired autophagic flux and alleviated liver injuries in ACLF mice, but these effects were abolished when autophago-lysosomal maturation was inhibited by leupeptin (leu), suggesting that MSCs exerted their hepatoprotective function in a pro-autophagic dependent manner. Moreover, we described a connection between transcription factor EB (TFEB) and autophagic activity in this context, as evidenced by increased nuclei translocation of TFEB elicited by MSCs were capable of promoting liver autophagy. Mechanistically, we confirmed that let-7a-5p enriched in MSCs derived exosomes (MSC-Exo) could activate autophagy by targeting MAP4K3 to reduce TFEB phosphorylation, and MAP4K3 knockdown partially attenuates the effect of anti-let-7a-5p oligonucleotide via decreasing the inflammatory response, in addition, inducing autophagy. Altogether, these findings revealed that the hepatoprotective effect of MSCs may partially profit from its exosomal let-7a-5p mediating autophagy repairment, which may provide new insights for the therapeutic target of ACLF treatment.

Liver Transplantation as a Cornerstone Treatment for Acute-On-Chronic Liver Failure.

Acute-on-chronic liver failure (ACLF) is a distinct clinical syndrome, characterized by acute decompensation (AD) of liver cirrhosis, severe systemic inflammation, intra- and extrahepatic organ failures, and a high short-term mortality. Liver transplantation (LT) is a potentially life-saving treatment for patients with decompensated liver cirrhosis and, due to the high mortality rates, particularly for ACLF patients. In the last decade, a plethora of studies has produced compelling evidence in favor of LT in ACLF, demonstrating high post-LT survival rates and excessive waitlist mortality. The importance of LT in these patients is underscored by the fact that no specific therapy for ACLF is available yet, rendering expeditious life-saving LT to be the only feasible treatment option for some ACLF patients. This review aims to provide an overview on pathophysiology, clinical trajectory, and clinical management of ACLF and to delineate the current literature regarding perspectives and limitations of LT as a life-saving treatment option for ACLF patients.