Unknown Etiology Research Articles

Sarcoidosis in a young adult: A rare sequelae of COVID‐19 infection

Key Clinical MessageThis case illustrates sarcoidosis as a potential complication of COVID‐19, highlighting the need for a comprehensive diagnostic approach, including histopathology and prolonged monitoring, to distinguish it from post‐COVID fibrosis. Further research is crucial to elucidate these associations and understand their underlying mechanisms.AbstractSevere Acute Respiratory Syndrome Coronavirus‐ 2 (SARS‐CoV‐2), a positive‐sense single‐stranded RNA virus, causes COVID‐19 and has been linked to autoimmune disorders. Sarcoidosis is a multi‐system disease that is frequently triggered by infections. It is characterized by non‐necrotizing granulomas in multiple organs. We present a case of sarcoidosis as rare sequelae of COVID‐19. A 26‐year‐old man presented with mild COVID‐19 symptoms, followed by prolonged fever and cough despite initial therapy, prompting a provisional diagnosis of post‐COVID fibrosis. A subsequent assessment at a tertiary hospital revealed dyspnea, weight loss, and abnormal chest imaging, all of which were consistent with pulmonary sarcoidosis with pulmonary tuberculosis as a differential diagnosis. A biopsy taken during bronchoscopy confirmed pulmonary sarcoidosis and treatment with inhalation steroids resulted in symptom relief, which was followed by remission with oral steroid therapy. Sarcoidosis is a systemic disease of unknown etiology, characterized by non‐necrotizing granulomas in multiple organs. It may be triggered by infections and involves an abnormal immune response. COVID‐19 can potentially initiate sarcoidosis, with both sharing common immune mechanisms. Diagnosis involves imaging and biopsy, and treatment typically includes glucocorticoids and regular monitoring. This case report emphasizes the potential link between COVID‐19 and autoimmune conditions like sarcoidosis, highlighting the need for a comprehensive diagnostic approach and long‐term observation to distinguish between sarcoidosis and post‐COVID fibrosis.

Rapidly destructive hip osteoarthritis: a diagnosis not to miss.

This review illustrates the imaging features of rapidly destructive hip osteoarthritis (RDHO) across different imaging modalities. RDHO is a rare joint disease of unknown aetiology resulting in rapid deterioration of the hip joints. Patients often present with severe hip pain and can progress to complete joint destruction in 6 months to 3 years causing disability. Since its clinical and imaging features often overlap with other conditions, the diagnosis is easily missed in daily practice. The purpose of this paper is to outline the characteristic imaging features of RDHO, aiming to enhance awareness of this disease entity and promote timely treatment for patients. Sequential radiographs are particularly important in demonstrating the rapid progression of radiographic findings and with the early recognition of characteristic features, diagnosis can be made to avoid treatment delay. Although CT scan is not necessary for diagnosis, it is useful in evaluating the extent of joint destruction and guiding surgical planning. MRI can provide additional information and rule out other pathologies with similar symptoms. Overall, radiographs, CT and MRI are common modalities used in the evaluation of RDHO.

Reduced WNT4 expression in normal skin fibroblasts leads to ‘Dupuytren-like’ changes in the transcriptome

BackgroundDupuytren's disease (DD) is a fibro-proliferative disorder of unknown aetiology. Previous studies have implicated multiple WNT signalling genes/proteins in Dupuytren pathology, including WNT4. However, it is not yet clear whether WNT signalling dysregulation plays an important role in the initiation of the disease or progression. The aim of this study was to determine if loss of WNT4 expression triggered ‘Dupuytren-like’ changes in the transcriptome of healthy skin fibroblasts. MethodsFibroblasts were isolated from the wrists of healthy adult males and from the wrists and disease cord tissue from males in a family positive for Dupuytren's disease. Normal skin fibroblasts from healthy controls were treated with WNT4 siRNA and scrambled controls. RNASeq was used to analyse the transcriptomes of disease and non-disease fibroblasts from patients with Dupuytren's as well as in siRNA treated and non-treated control fibroblasts. ResultsAnalysis of the transcriptomes from DD patient and normal skin fibroblasts showed significant differences, including in WNT4 expression. Downregulation of WNT4 in normal skin fibroblasts using siRNA led to ‘DD-like’ changes in the transcriptome. ConclusionIn people susceptible to DD WNT4 is downregulated even in non-fibrotic fibroblasts. Knockdown of WNT4 in normal fibroblasts led to changes that made cells ‘DD-like’. This study shows that WNT4 is down regulated in ‘non-disease’ cells, and that downregulating WNT4 in normal skin fibroblasts leads to widespread ‘DD like’ changes in the transcriptome, suggesting WNT4 downregulation is a key driver of DD.

Neutrophil extracellular traps activate Notch–γ-secretase signaling in hidradenitis suppurativa

BackgroundHidradenitis suppurativa (HS) is an inflammatory chronic skin disorder of unknown etiology characterized by inflamed abscess-like nodules and boils resulting in sinus tract formation, tissue scarring and massive infiltration of neutrophils. Multiple lines of evidence have highlighted the potential association between alterations in the Notch pathway and HS pathogenesis, but the mechanisms remain incompletely characterized. ObjectiveHerein, we aim to elucidate the role of neutrophil extracellular traps in Notch-γ-secretase, signaling. MethodsTwenty-six HS lesional tissues, primary HS macrophages and skin fibroblasts were interrogated by quantitative PCR, western blot, and Elisa analyses. γ-Secretase, and TACE activities were measured in HS skin lesions, macrophages and skin fibroblasts. Immunofluorescence and RNAscope analyzes were performed in HS and control skin. ResultsA prominent presence of Notch ligands, DLL4 and JAG2 were detected at the protein and mRNA levels in HS skin lesion when compared to control. Levels of DLL4, JAG1, cit-H3-DNA and γ-secretase activity correlated with HS disease severity. Additionally, significantly elevated levels of Notch ligands and γ-secretase activity were found in dissected sinus tracts when compared to the rest of HS tissue. Immunofluorescence microscopy in HS skin lesions showed activation of Notch 1 signaling in macrophages and skin fibroblasts. Neutrophil extracellular traps (NETs) purified from HS patients displayed elevated levels of DLL4. HS-NETs activated the Notch pathway in macrophages and dermal fibroblasts isolated from HS patients. HS skin fibroblasts displayed elevated levels of CD90 and DPP4 in association with increased migratory capacity and Notch activation. Inhibition of Notch decreased migratory capacity and pro-fibrotic markers in HS fibroblasts. ConclusionThese data support a pathogenic connection between NETs, Notch- γ-secretase activation and the release of pro-fibrotic molecules that promote dysregulation of macrophages and skin fibroblasts in HS. Unveiling the relevance of these molecular events not only expands our understanding of HS but also opens new venues for the development of targeted therapies to address the fibrotic complications of advanced stages of HS.

Fast Viral Diagnostics: FTIR-Based Identification, Strain-Typing, and Structural Characterization of SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered an ongoing global pandemic, necessitating rapid and accurate diagnostic tools to monitor emerging variants and preparedness for the next outbreak. This study introduces a multidisciplinary approach combining Fourier Transform Infrared (FTIR) microspectroscopy and Machine learning to comprehensively characterize and strain-type SARS-CoV-2 variants. FTIR analysis of pharyngeal swabs from different pandemic waves revealed distinct vibrational profiles, particularly in nucleic acid and protein vibrations. The spectral wavenumber range between 1150 and 1240 cm-1 was identified as the classification marker, distinguishing Healthy (noninfected) and infected samples. Machine learning algorithms, with neural networks exhibiting superior performance, successfully classified SARS-CoV-2 variants with a remarkable accuracy of 98.6%. Neural networks were also able to identify and differentiate a small cohort infected with influenza A variants, H1N1 and H3N2, from SARS-CoV-2-infected and Healthy samples. FTIR measurements further show distinct red shifts in vibrational energy and secondary structural alterations in the spike proteins of more transmissible forms of SARS-CoV-2 variants, providing experimental validation of the computational data. This integrated approach presents a promising avenue for rapid and reliable SARS-CoV-2 variant identification, enhancing our understanding of viral evolution and aiding in diagnostic advancements, particularly for an infectious disease with unknown etiology.

Comparative study of non-suppurative meningoencephalitis in cattle in Southern Brazil.

Viral neurologic diseases are common in cattle, although most non-suppurative meningoencephalitis (NSM) remains etiologically unknown. We compared the epidemiological, clinical, and pathological data among 79 cases of rabies, 12 cases of NSM of unknown etiology (NSM-UE), and 8 cases of herpetic meningoencephalitis previously diagnosed in cattle in Southern Brazil. Neurological clinical signs were similar among rabies and NSM-UE and different in cattle with herpetic meningoencephalitis. Only two herpetic meningoencephalitis cases had gross lesions in the central nervous system, characterized by malacia and hemorrhage. Histologically, all three groups had mild to severe multifocal infiltrates of lymphocytes, plasma cells, and macrophages/microglial cells in the Virchow-Robin space, neuropil, and leptomeninges, and gliosis. Other findings included malacia and eosinophilic intracytoplasmic inclusion in rabies, and malacia and intranuclear amphophilic inclusion in herpetic meningoencephalitis. By immunohistochemistry, the predominant inflammatory cells in all cases were T lymphocytes, followed by macrophages/microglial cells, B lymphocytes, and astrocytes. The T lymphocyte count showed statistically significant differences between the diseases. Our results revealed few differences between the groups. Although the etiological agent involved has not been identified in cases of NSM-UE, the characteristics observed in this study showed similarity with viral diseases.

Organochlorine pesticides and their markers of exposure in serum and urine of children from a nodding syndrome hotspot in northern Uganda, east Africa

Nodding syndrome (NS) is a neurologic disorder of unknown etiology characterized by vertical head nodding that has affected children aged 5–18 years in East Africa. Previous studies have examined relationships with biological agents (e.g., nematodes, measles, and fungi), but there is limited data on the possible contributions of neurotoxic environmental chemicals frequently used as pesticides/insecticides to the development and progression of this disorder. We examined the levels of persistent organochlorine pesticides (OCPs) in children (5–18 years old) from Kitgum District, Northern Uganda. These children previously lived in internally displaced people's (IDP) camps, where they were exposed to various health risks, including contaminated food and water. Exposure to OCPs through contaminated food and water is postulated here as a potential contributor to NS etiology. We analyzed serum (n = 75) and urine (n = 150) samples from children diagnosed with NS, and from seizure-free household controls (HC), and community controls (CC). Samples were extracted using solid-phase extraction (SPE) and extracts were analyzed for OCPs using gas chromatography with a triple quadrupole mass spectrometry (GC-MS/MS). Mean levels of total (∑) ∑OCPs in serum samples from NS, HC and CC subjects were 23.3 ± 2.82, 21.1 ± 3.40 and 20.9 ± 4.24 ng/mL, respectively, while in urine samples were 1.86 ± 1.03, 2.83 ± 1.42, and 2.14 ± 0.94 ng/mL, respectively. Correlation and linear regression analysis indicated that potential markers for ∑hexachlorocyclohexanes (HCHs), ∑chlordane compounds (CHLs), ∑endosulfan and ∑dichlorodiphenyltrichloroethanes (DDTs) were γ-HCH, heptachlor-exo-epoxide, endosulfan-α and p,pʹ-DDD in NS cases while in controls were α –HCH, heptachlor, endosulfan-α and p,pʹ-DDE, respectively. Since, in some instances, higher OCP levels were found in controls vs. NS cases, we conclude that exposure to organochlorine pesticides is unlikely to be associated with the etiology of NS.

Recurrent symptomatic abdominopelvic cystic lesions of unknown etiology treated with image-guided sclerotherapy: A case report

This case report highlights the diagnostic approach and treatment for 30 cm bilateral multiloculated pelvic peritoneal cystic masses. The patient had a history of spina bifida with ventriculoperitoneal shunt placement and neurogenic bladder with partial cystectomy and ileal conduit diversion. The cysts were suspected to be peritoneal inclusion cysts. Due to prior failed surgical intervention, the patient was treated with image-guided sclerotherapy.

Optimizing ketogenic diet therapy for childhood epilepsy: Identifying key factors for seizure control and psychomotor enhancement.

To identify key factors influencing the therapeutic efficacy of the ketogenic diet (KD) for children with drug-resistant epilepsy and elucidate their interconnected relationships to optimize clinical practice. Participants were selected from children receiving KD treatment at West Second University Hospital of Sichuan University from September 2015 to October 2023. Clinical factors pre-KD and post-KD (at the third month) were analyzed systematically using an analytical framework. Descriptive analyses, univariate analyses, and multivariate regression analyses were performed for the entire cohort and subgroups of genetic and non-genetic (i.e., structural and unknown) etiologies. Thereby, the most significant predictors were identified for each relevant dependent variable. Path analysis diagrams were used for visual representation. Of 156 patients, genetic etiology was prevalent (38.5%). In the genetic subgroup, channelopathies predicted lower baseline seizure frequency and increased chance of seizure freedom with KD. Frequent seizures and complex history of anti-seizure medications (ASMs) predicted severe baseline psychomotor abnormalities. Younger age at KD initiation benefited psychomotor improvement. In the non-genetic subgroup, lower baseline seizure frequency increased the likelihood of seizure freedom post-KD. Concurrent use of multiple ASMs helped achieve ≥50% seizure reduction. Boys were more likely to experience psychomotor improvement. A significant correlation was found between ≥50% seizure reduction and psychomotor improvement in both subgroups. Delayed KD initiation (longer epilepsy duration at KD start) was related to a greater number of ASMs used, infrequent seizures, and older age at epilepsy onset. In addition, patients with channelopathies had delayed initiation of KD. Children with genetic epilepsy display more pronounced characteristics of epileptic encephalopathy. Early KD intervention is crucial for channelopathies, notably SCN1A variants. For other drug-resistant epilepsy cases, KD alongside diverse ASMs may improve seizure control and developmental outcomes. However, the patient population benefiting most from early KD tends to start the treatment later, urging a re-evaluation of KD decision-making paradigms.

Impact of bone marrow fibrosis on outcomes of allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia.

Bone marrow fibrosis (BMF) of unknown etiology was common in hematological malignancies, but its prognostic value for acute myeloid leukemia (AML) is unclear. We interrogated data from 532 newly diagnosed subjects with AML receiving allogeneic hematological stem cell transplantation to evaluate the prognostic impact of BMF on transplant outcomes. Using the European consensus on the grading of BMF at diagnosis, 255 (48%) subjects were BMF-0, 209 (39%), BMF-1 and 68 (13%), BMF-2-3. Subjects with BMF-2-3 had poor overall survival (P < 0.001), disease-free survival (P < 0.001) and a higher incidence of relapse (CIR, P < 0.001). Multi-variable analyses in subjects achieving pre-transplant complete remission showed BMF-2-3 was an independent risk factor for CIR (Hazard Ratio [HR] = 2.17, (95% CI, 1.11, 4,24); P = 0.02). Furthermore, BMF-2-3 group showed delayed neutrophil and platelet engraftment and delayed B cell recovery post-transplantation. These findings demonstrate the significance of BMF in transplant outcomes and attract more attention to AML with BMF.

Gastrointestinal Manifestations of Sarcoidosis: A State-of-the-Art, Comprehensive Review of the Literature-Practical Clinical Insights and Many Unmet Needs on Diagnosis and Treatment.

This comprehensive literature review explores the involvement of the gastrointestinal (GI) tract in sarcoidosis, a multisystem granulomatous disorder of unknown etiology. GI sarcoidosis presents a diagnostic and therapeutic challenge due to its rarity and nonspecific clinical manifestations, including overlap with other gastrointestinal diseases. We conducted a comprehensive screening of articles addressing the clinical features, diagnostic approaches, and treatment strategies for GI sarcoidosis. Our findings reveal that GI sarcoidosis can affect any part of the gastrointestinal tract, with the stomach and small intestine being the most involved. Clinical presentations range from asymptomatic cases to severe complications such as obstruction and perforation, with reflux being a common symptom. Diagnosis is often delayed due to the nonspecific nature of symptoms and the need for histopathological confirmation. Therapeutic approaches are poorly defined, typically involving corticosteroids as the mainstay of treatment. However, the long-term efficacy and safety of these treatments remain uncertain in this patient group, given the significant risks and complications associated with prolonged glucocorticoid therapy. There is a clear need to develop accurate diagnostic protocols to distinguish GI sarcoidosis from other conditions and to establish standardized therapeutic guidelines to optimize patient outcomes. Further research is essential to enhance our understanding and management of this complex condition.

Hydrogel Use in Osteonecrosis of the Femoral Head.

Osteonecrosis of the femoral head (ONFH) is a vascular disease of unknown etiology and can be categorized mainly into two types: non-traumatic and traumatic ONFH. Thus, understanding osteogenic-angiogenic coupling is of prime importance in finding a solution for the treatment of ONFH. Hydrogels are biomaterials that are similar to the extracellular matrix (ECM). As they are able to mimic real tissue, they meet one of the most important rules in tissue engineering. In ONFH studies, hydrogels have recently become popular because of their ability to retain water and their adjustable properties, injectability, and mimicry of natural ECM. Because bone regeneration and graft materials are very broad areas of research and ONFH is a complex situation including bone and vascular systems, and there is no settled treatment strategy for ONFH worldwide, in this review paper, we followed a top-down approach by reviewing (1) bone and bone grafting, (2) hydrogels, (3) vascular systems, and (4) ONFH and hydrogel use in ONFH with studies in the literature which show promising results in limited clinical studies. The aim of this review paper is to provide the reader with general information on every aspect of ONFH and to focus on the hydrogel used in ONFH.

High prevalence of hepatitis E and rat hepatitis E viruses in wastewater in Gothenburg, Sweden

Hepatitis E virus (HEV) and Rat Hepatitis E virus (RHEV), recognized for their zoonotic potential, pose significant public health concerns. Our previous research identified both viruses in effluent wastewater in Gothenburg, Sweden. However, there are lingering inquiries regarding the prevalence and genetic diversity of these viruses in influent wastewater, as well as the utility of wastewater surveillance in elucidating their community circulation dynamics. To address these knowledge gaps, we conducted weekly collection of wastewater samples at the Rya wastewater treatment plant in Gothenburg throughout 2023. The concentrations of HEV and RHEV were quantified using quantitative polymerase chain reaction (qPCR). Additionally, two semi/nested-PCR were utilized to amplify viral strains. Furthermore, HEV strains from patients within the same region, as well as other regions in Sweden in 2023, were incorporated into the analysis. Remarkably, we observed a high prevalence of HEV (86%) and RHEV (98%) in wastewater samples, with the majority of HEV sequences identified as subtype 3c/i (9/12). In contrast, HEV subtype 3f was the most sequenced among clinical patient samples (6/12). Notably, previously unreported HEV-3b and unclassified strains were detected in wastewater. Almost all RHEV strains (20/21) were clustered into European groups, with none of the RHEV genetically close to strains previously found in human cases. The notable discordance in prevalence and identified subtypes of HEV-3 in wastewater compared to clinical samples suggests either a significant underdiagnosis of HEV infections or differences in viral loads and shedding durations among humans between HEV-3 subtypes. This underscores the urgent need for improved diagnostic techniques and heightened awareness of HEV transmission dynamics. Furthermore, the consistent detection of RHEV in wastewater underscores the necessity for further investigations to assess the potential role of RHEV in hepatitis cases of unknown etiology, given that most currently available clinical diagnostic assays fail to detect RHEV.

Therapeutic effects of a new bithiophene against aluminum -induced Alzheimer’s disease in a rat model: Pathological and ultrastructural approach

Alzheimer’s disease (AD) remains of unknown etiology and lacks a cure. This study aimed to evaluate the therapeutic potential of a novel bithiophene derivative at two doses against AlCl3-induced AD in a rat model. Adult male rats (Rattus norvegicus) were divided into six groups (n=6): Group one consisted of naïve animals, group two received bithiophene (1 mg/kg) every other day for 30 days, and groups 3–6 were subjected to AlCl3 (100 mg/kg, equivalent to 20.23 mg Al3+) for 45 consecutive days. Groups four and five received low (0.5 mg/kg) or high (1 mg/kg) doses of bithiophene, respectively. Group six received memantine (20 mg/kg) daily for 30 days. All treatments were administered orally. Aluminum exposure resulted in severe degeneration of both histological and ultrastructural aspects of cells. Administration of the low dose of bithiophene significantly restored the number of CA1 pyramidal cells and the thickness of the stratum granulosum of the dentate gyrus. However, the high dose of bithiophene increased viable CA1 pyramidal cell numbers significantly without restoring the thickness of the stratum granulosum or reducing vacuolization or pyknotic changes. The low dose of bithiophene restored the normal histological and cytological structure of both cortical and hippocampal neurons affected by dementia. Further investigation is required to explore the molecular mechanisms underlying the ameliorative effects on Alzheimer’s disease-induced deteriorations in the cortex and hippocampus.

Different imaging techniques’ diagnostic efficacy for Crohn’s disease activity and external validation and comparison of MDCTAs, SES-CD and IBUSSAS

BackgroundCrohn’s disease (CD) is a chronic inflammatory disease of the digestive tract with unknown etiology. It follows a relapse-remission pattern, making disease activity assessment crucial for treatment. Our study aims to evaluate the diagnostic accuracy of various imaging modalities and to validate and compare the International Bowel Ultrasound Segmental Activity Score (IBUS-SAS), the multidetector computed tomography enterography score (MDCTEs), and the simplified endoscopic activity score for Crohn’s disease (SES-CD).MethodsWe assessed diagnostic performance using the CD Activity Index (CDAI). We first categorized patients into remission and active groups. For those in the active stage, we further categorized them into mild/moderate and severe activity groups. We used Spearman rank correlation to evaluate the relationships among IBUS-SAS, bowel wall thickness (BWT), Color Doppler imaging signal (CDS), inflammatory fat (i-fat), bowel wall stratification (BWS), and clinical inflammatory indicators.ResultsA total of 103 CD patients were evaluated. The IBUS-SAS cut-off for remission and activity was 23.8, with an AUC of 0.923, sensitivity of 91.4%, and specificity of 84.8%. The SES-CD had an AUC of 0.801, sensitivity of 62.9%, and specificity of 84.4% at a cut-off of 4.5. The MDCTEs showed an AUC of 0.855, sensitivity of 77.1%, and specificity of 75.8% for a cut-off of 6.5. The Delong test revealed significant differences in diagnostic efficacy when comparing IBUS-SAS to SES-CD and IBUS-SAS to MDCTEs. In the group of mild or moderate-to-severe active, the IBUS-SAS had an AUC of 0.925, sensitivity of 83.7%, and specificity of 88.9% at a cut-off of 40. The SES-CD exhibited an AUC of 0.850, sensitivity of 90.7%, and specificity of 70.4% at a cut-off of 8.5. MDCTEs showed an AUC of 0.909, sensitivity of 83.7%, and specificity of 85.2% at a cut-off of 8.5. During Delong test, the IBUS-SAS, MDCTEs, and SES-CD showed no significant differences in assessing moderate-to-severe activity. Both IBUS-SAS and ultrasound parameters correlated with certain serum indicators (p < 0.05), although only weakly to moderately (all r < 0.5).ConclusionThe IBUS-SAS, MDCTEs and SES-CD can evaluate disease remission/active and mild/moderate-to-severe active in CD, and IBUS-SAS offers the potential to precisely define CD activity.

Current Status and Outcomes of Living Donor Liver Transplantation for Pediatric Acute Liver Failure: Results From a Multicenter Retrospective Study Over Two Decades.

Although the outcomes of living donor liver transplantation (LDLT) for pediatric acute liver failure (PALF) have improved, patient survival remains lower than in patients with chronic liver disease. We investigated whether the poor outcomes of LDLT for PALF persisted in the contemporary transplant era. We analyzed 193 patients who underwent LDLT between December 2000 and December 2020. The outcomes of patients managed in 2000-2010 (era 1) and 2011-2020 (era 2) were compared. The median age at the time of LDLT was 1.2 years both eras. An unknown etiology was the major cause in both groups. Patients in era 1 were more likely to have surgical complications, including hepatic artery and biliary complications (p = 0.001 and p = 0.013, respectively). The era had no impact on the infection rate after LDLT (cytomegalovirus, Epstein-Barr virus, and sepsis). The mortality rates of patients and grafts in era one were significantly higher (p = 0.03 and p = 0.047, respectively). The 1- and 5-year survival rates were 76.4% and 70.9%, respectively, in era 1, while they were 88.3% and 81.9% in era 2 (p = 0.042). Rejection was the most common cause of graft loss in both groups. In the multivariate analysis, sepsis during the 30 days after LDLT was independently associated with graft loss (p = 0.002). The survival of patients with PALF has improved in the contemporary transplant era. The early detection and proper management of rejection in patients, while being cautious of sepsis, should be recommended to improve outcomes further.

Interleukin 18 (-137G/C, -607C/A) Polymorphisms as Genetic Biomarkers of Susceptibility to Systematic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown etiology. Several studies have suggested that interleukin-18 (IL-18) is associated with SLE pathogenesis. The genotype distribution of IL-18 promoter polymorphisms differs among ethnic populations. The present study aimed to investigate the correlation between IL-18 polymorphisms at positions -137 and -607 in patients situated in Northeastern Iran. This case-control study examined the prevalence of IL-18 -137C/G and -607C/A polymorphic variants among 95 SLE patients referred to the Department of Rheumatology, who were referred to the general clinics of Ghaem Hospital and Imam Reza Hospital in Mashhad, Iran, were included in the study. In addition, 100 healthy individuals were included in the control group. DNA from whole blood was extracted by the salting-out method using a commercial kit (Biogene, US). Allelic and genotypic frequencies of polymorphisms (-137G/C, -607C/A) in the IL-18 promoter gene were analyzed using a polymerase chain reaction (PCR)-based amplification refractory mutation system (ARMS) method. The results of this study demonstrated that the frequency of SLE patients with the homozygous C/C genotype of the IL-18 promoter gene at position -137 was significantly higher than that of the homozygous G/G genotype (P < 0.001) in normal controls. Furthermore, the polymorphism analysis performed illustrated a significant association between (-137G/C) and (-607C/A) polymorphisms in the IL-18 promoter gene and SLE (P < 0.005). These results indicated that the 607A/A and 137C/C polymorphisms are more prevalent in SLE. Further research involving larger sample sizes from various populations is necessary to elucidate the role of these polymorphisms and the distribution of alleles in SLE patients.

Adrenocorticotropic hormone therapy alters Q-albumin ratios in patients with infantile epileptic spasms syndrome of unknown etiology

PurposeInfantile epileptic spasms syndrome (IESS) with epileptic spasms as the main seizure type, is treated with adrenocorticotropic hormone (ACTH). This study, for the first time, examines the effects of epileptic spasms and ACTH on blood-brain barrier (BBB) permeability in patients with IESS of unknown etiology. MethodsWe prospectively evaluated the changes in BBB permeability in patients with IESS of unknown etiology at the Saitama Children's Medical Center between February 2012 and February 2024. We compared the levels of serum-albumin, cerebrospinal fluid (CSF)-albumin, Q-albumin, and CSF-neuron-specific enolase (NSE) before and after ACTH therapy. We also assessed the correlation between the frequency of epileptic spasms and these markers. ResultsOverall, 16 patients with IESS (8 males) were included in the study. The median age at IESS onset was 5 (range, 2–9) months. The median duration between the epileptic spasms onset and the serum and CSF sample examination before ACTH therapy was 26 (range, 1–154) days. After ACTH therapy, CSF-albumin and Q-albumin levels significantly decreased (CSF-albumin: 13.5 (9.0–32.0) mg/dL vs 11.0 (7.0–19.0) mg/dL, p = 0.001. Q-albumin: 3.7× 10−3 (2.2 × 10−3-7.3 × 10−3) vs 2.8× 10−3 (1.9 × 10−3-4.5 × 10−3), p = 0.003). No correlation was observed between the epileptic spasms frequency and levels of serum-albumin, CSF-albumin, Q-albumin, and CSF-NSE (Spearman's coefficient: r = 0.291, r = 0.141, r = 0.094, and r = −0.471, respectively). ConclusionACTH therapy is one of the factors that play a role in restoring BBB permeability in patients with IESS of unknown etiology. Our findings may be useful in elucidating the mechanism of ACTH action and IESS pathophysiology.

Different patterns of persistent somatic symptoms after COVID-19 reported by the Dutch media and the general population

ObjectivePost COVID-19 condition is characterized by persistent symptoms after COVID-19 with yet unknown etiology. To explore whether media-related nocebo effects potentially contribute to post COVID-19 condition, we studied in an observational cohort whether frequencies of media coverage of symptoms after COVID-19 corresponded with prevalence rates of these symptoms in participants from a general population cohort diagnosed with COVID-19. MethodsPrevalence rates and typology of symptoms after COVID-19 in the general population (N = 4231), adjusted for prevalence rates in a matched non-infected control population (n = 8462) were calculated by using data on 23 symptoms from the Lifelines COVID-19 Cohort collected between March 2020 and August 2021. Media coverage of post COVID-19 condition was assessed by coding 1266 Dutch post COVID-19-related news articles (inter-rater-κ ≥ 0.75), published during the corresponding timeframe. Herein, we assessed whether the same 23 symptoms were mentioned as being related to post COVID-19 condition. ResultsCore post COVID-19 condition symptoms were mentioned in 390 (30.8%) articles. Five of the ten core symptoms were mentioned by 10 or fewer articles. Ageusia/anosmia was most often persistently increased in COVID-19-positive participants (7.6%), yet was mentioned in 80 (6.3%) articles. General tiredness and breathing difficulties were frequently mentioned, in 23.9% and 17.1% of the articles respectively, while these were not the most frequently increased symptoms reported by participants (4.9% and 2.4%). ConclusionIf post COVID-19 condition was predominantly attributable to nocebo effects, its symptom profile would be expected to reflect levels of media coverage for symptoms after COVID-19. However, our findings do not support this.

MODY Only Monogenic? A Narrative Review of the Novel Rare and Low-Penetrant Variants.

Maturity-onset diabetes of the young (MODY) represents the most frequent form of monogenic diabetes mellitus (DM), currently classified in 14 distinct subtypes according to single gene mutations involved in the differentiation and function of pancreatic β-cells. A significant proportion of MODY has unknown etiology, suggesting that the genetic landscape is still to be explored. Recently, novel potentially MODY-causal genes, involved in the differentiation and function of β-cells, have been identified, such as RFX6, NKX2.2, NKX6.1, WFS1, PCBD1, MTOR, TBC1D4, CACNA1E, MNX1, AKT2, NEUROG3, EIF2AK3, GLIS3, HADH, and PTF1A. Genetic and clinical features of MODY variants remain highly heterogeneous, with no direct genotype-phenotype correlation, especially in the low-penetrant subtypes. This is a narrative review of the literature aimed at describing the current state-of-the-art of the novel likely MODY-associated variants. For a deeper understanding of MODY complexity, we also report some related controversies concerning the etiological role of some of the well-known pathological genes and MODY inheritance pattern, as well as the rare association of MODY with autoimmune diabetes. Due to the limited data available, the assessment of MODY-related genes pathogenicity remains challenging, especially in the setting of rare and low-penetrant subtypes. In consideration of the crucial importance of an accurate diagnosis, prognosis and management of MODY, more studies are warranted to further investigate its genetic landscape and the genotype-phenotype correlation, as well as the pathogenetic contribution of the nongenetic modifiers in this cohort of patients.