Severe Manifestations Research Articles

SARS-CoV-2 induced vitamin D deficiency and psychological stress: a manifestation of autoimmune disease onset.

The global SARS-CoV-2 pandemic significantly altered lifestyles, access to healthcare, and social interactions, introducing unprecedented physical and psychological stress all over the world. This study explores the relationship between psychological stress, vitamin D (Vit-D) levels, and autoimmune connective tissue diseases, including systemic lupus erythematosus, systemic sclerosis, polymyositis, dermatomyositis, and rheumatoid arthritis. The analysis was based on over one million patient data points derived from anti-nuclear antibody (ANA) testing conducted both before and during the COVID-19 pandemic 2017-2021. In a subset of patients, longitudinal data were collected bi-yearly to yearly over 5-8 years using the same three-month criteria. The dataset was analyzed using GraphPad Prism9 using paired t-tests or ordinary one-way ANOVA with a significance threshold of p < 0.05 to ensure robust correlations between the variables. Data indicated that Vit-D levels peaked between 2017 and 2019 before declining, while ANA data demonstrated a rise in autoimmune connective tissue disease cases during the pandemic, reaching a peak in 2021. A clear correlation was observed, with autoimmune disease incidence increasing as Vit-D levels decreased. In-depth case analysis revealed that declining Vit-D levels preceded higher ANA titers and increased autoimmune disease severity, whereas improvements in Vit-D levels were associated with reduced ANA titers and less severe disease manifestations. The findings suggest that maintaining mental health and ensuring adequate Vit-D supplementation could be essential strategies for mitigating autoimmune disease risks and maintaining immune stability, particularly in pandemic scenarios. Clinically, these results underscore the need for early interventions targeting both psychological well-being and Vit-D levels to reduce the burden of autoimmune diseases.

Special considerations for hidradenitis suppurativa in skin of colour: A review of literature

AbstractHidradenitis suppurativa, a chronic inflammatory skin condition, disproportionately affects individuals with skin of colour (SOC), particularly African Americans. Despite the increased prevalence in SOC, racial minorities are underrepresented in HS clinical trials, limiting our understanding of treatment efficacy. The purpose of this narrative review is to discuss the current literature regarding the clinical presentation, comorbidities, and management of HS in SOC individuals. A PubMed search was conducted using the terms Hidradenitis suppurativa, comorbidities, skin of colour, African–American, Hispanic, and quality of life with relevant studies written in English and pertaining to the demographics and clinical trials were included. African American patients with HS tend to experience more severe disease manifestations, higher rates of comorbidities like inflammatory bowel disease and anaemia, increased healthcare utilisation, and a greater likelihood of surgical interventions. While the current literature provides extensive information about African Americans regarding comorbidities and disease prevalence, there is a lack of research on Hispanic and other ethnic groups. For future research, it is important to broaden our focus to include various ethnic groups. Addressing these disparities requires focused interventions, inclusive clinical research initiatives, and healthcare policies tailored to the specific needs of patients with skin of colour.

S892 Prevalence of Severe Gastrointestinal Manifestations in Dermatomyositis

S892 Prevalence of Severe Gastrointestinal Manifestations in Dermatomyositis

Eight induced pluripotent stem cell lines (iPSCs) derived from two patients with Leukocyte adhesion deficiency Type I (LAD I) with mutations in the ITGB2 gene

Leukocyte Adhesion Deficiency Type I (LAD I) is a rare inborn error of immunity caused by mutations in the ITGB2 gene coding for β2-integrin CD18 on the surface of leukocytes. Affected patients display severe clinical manifestations with life threatening infections and inflammatory complications due to an impaired ability of leukocytes to transmigrate from the blood vessel to the tissue. Here we describe the generation of eight induced pluripotent stem cell lines from two patients with LAD I and mutations in the ITGB2 gene. With this project we contribute patient individualized cell lines for explorative research in a rare disease

The outcome of coronavirus disease 2019 in hospitalized patients with diabetes mellitus at Assiut University Hospital

Rationale The chronic nature of diabetes renders it a risk factor for lower respiratory tract infections, adversely impacting patient prognosis. Objective This study aimed to investigate the influence of diabetes on the outcomes of coronavirus disease 2019 (COVID-19) patients. Patients and methods This prospective cohort study enrolled 160 patients admitted and diagnosed with COVID-19. Patients were categorized according to glycated hemoglobin level into two groups: diabetic and nondiabetics (80 patients each). The COVID-19 severity index was calculated for all patients. Follow-up of their in-hospital stay and incidence of complications was documented. Results It was found that diabetic patients had a significantly higher percentage of severe COVID-19 cases (83.8 vs. 61.3%) [odds ratio (OR)=1.89, 95% confidence interval (CI)=1.02–3.48]. The diabetic group had higher rates of ICU admission (OR=2.21, 95% CI=1.06–4.57), invasive mechanical ventilation (OR=3.75, 95% CI=1.321–10.803), and mortality (HR=1.69, 95% CI=1.132-2.514) compared with nondiabetic patients (33.8 vs. 18.8%, 20 vs. 6%, and 41.5 vs. 21.2%, respectively). From the nondiabetic group, 68.4% of prediabetic patients had hyperglycemia requiring insulin treatment during their hospital stay versus 31.6% of normoglycemic patients. Conclusion Diabetes mellitus is associated with more severe manifestations of the disease, increased complications, ICU admissions, ventilatory requirements, and mortality rates compared to nondiabetic individuals. COVID-19 is associated with poor glycemic control.

Juvenile Systemic Scleroderma: A comprehensive Review and Clinical Case Report from a Tertiary Care Hospital in India

Juvenile systemic sclerosis (JSSc) is a highly uncommon, chronic connective tissue disorder that affects multiple systems, marked by progressive deposition of collagen under the dermis, and various deep organs. Delay in diagnosis can cause irreversible vital organ damage, leading to severe morbidities and seriously affecting quality of life. We report a clinical case of a 9-year-old boy with extensive and diffuse skin manifestations with vascular, pulmonary, and gastrointestinal involvement. The sero-immunological test revealed positive ANA results and high titers of anti-topoisomerase (Scl-70) antibodies, indicative of severe manifestation of the disease. He was managed with systemic immunosuppression and other pharmacological and rehabilitative measures to prevent ongoing organ damage and alleviate the patient’s symptoms.

Reviewing Genetic Testing for Lupus: Implications for Nephritis

Genetic testing has significantly changed our understanding and treatment of systemic lupus erythematosus (SLE), particularly its severe manifestation, lupus nephritis (LN). Nephrology faces great difficulty with LN, which is characterized by severe inflammation and kidney damage. To create individualized treatments, it is essential to identify the genetic variables that influence the LN susceptibility and progression. This review highlights the importance of genetic testing in diagnosing and managing LN, covering genetic predispositions, common markers, the role of ethnicity, specific renal genes, and epigenetic factors. Key genetic markers such as HLA-DRB1, ITGAM, FCGR2A, and IRF5 have been linked to LN, impacting immune regulation and disease progression. Asians, African Americans, and Hispanics have greater prevalence rates of genetic susceptibility than Caucasians, suggesting that ethnicity plays a major role in genetic vulnerability. Genes like APOL1, PDGFRA, and HAS2 play vital roles in renal function and fibrosis, affecting disease outcomes. New treatment targets are provided by epigenetic mechanisms that control gene expression in LN, such as DNA methylation and histone alterations. The progress made in genome-wide association studies (GWAS) has led to the discovery of new genetic loci linked to LN, which has improved our knowledge of its pathogenesis. This review highlights the critical role of genetic testing in LN, emphasizing its potential to improve diagnosis, treatment, and patient outcomes through personalized medicine.

The New Spectrum of Plasmodium Vivax Malaria Severity: A Single-Center Experience

Plasmodium vivax malaria, once considered a benign and self-limiting disease, has emerged as a significant public health concern, with increasing reports of severe and even fatal cases. Objective: To evaluate the clinical severity and complications associated with Plasmodium vivax malaria in patients in Peshawar. Methods: A descriptive cross-sectional study was conducted at Lady Reading Hospital, Peshawar, for about two months. A total of 160 patients diagnosed with Plasmodium vivax malaria were enrolled. Participants were divided into two groups based on platelet count. Laboratory tests, including complete blood count, liver function tests, and Renal Function Tests were performed. Data were analyzed using SPSS version 20.0 , An Independent sample t-test was used to assess the significant difference between the two groups with statistical significance set at p&lt;0.05. Results: A total of 165 patients were included in the study. In the severe thrombocytopenia group (&lt;100,000/µL), there were 23 cases of anemia, jaundice (n=25), acute renal failure (n=7), cerebral malaria (n=2), seizures (n=1) and hypoglycemia (n=1). In the less severe thrombocytopenia group (&gt;100,000/µL), there were 14 cases of anemia, jaundice (n=17), and acute renal failure (n=2). The blood glucose level (p=0.37), systolic blood pressure (p=0.18) and pulse rate (p=0.21) revealed no significant differences between the two groups. Conclusions: It was concluded that severe thrombocytopenia in P. vivax malaria was associated with more severe clinical manifestations, with a few cases requiring transfusions. Patients with less severe thrombocytopenia had fewer complications

Radiological Assessment of Pulmonary Vascular Changes and Gastrointestinal Changes in COVID-19 Patients Referred to a Tertiary Health Care Centre in Chennai, India: A Prospective Cross-Sectional Study

Background: The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has led to significant morbidity and mortality worldwide since its emergence in 2019. While primarily a respiratory illness, COVID-19 can also affect other organ systems, including the vascular and gastrointestinal systems. COVID-19 infection is linked to both venous and arterial thrombosis, with numerous studies indicating a heightened risk of pulmonary embolism (PE) among patients. Autopsies have revealed pulmonary vasculature thrombosis and bowel ischemia in COVID-19 cases. Aim: This prospective cross-sectional study aimed to assess radiological pulmonary vascular changes, specifically pulmonary embolism (PE), and gastrointestinal changes in COVID-19 patients referred to a tertiary healthcare center in Chennai, India. Methods: CT pulmonary angiography (CTPA) and contrast-enhanced CT of the abdomen were conducted in 100 COVID-19 positive patients meeting the inclusion and exclusion criteria. Evaluation of pulmonary vascular changes and bowel changes was performed by a radiologist with five years of experience. Subsequently, statistical analysis was carried out to determine the significance of the relationship between COVID-19 patients and the occurrence of pulmonary vascular and bowel changes. Results: In our study, 11 patients exhibited pulmonary thromboembolism, and 7 patients showed significant bowel changes. There is a positive correlation between the prevalence of PE in COVID-19 patients. PE was diagnosed at a mean of 11 days from the onset of the disease. Out of 24 patients with severe acute respiratory illness (SARI), 7 showed PE in CTPA. Additionally, out of 10 mechanically ventilated patients, 7 had PE in CTPA. Among the 7 patients with bowel changes, 4 had PE in CTPA, indicating a significant association with PE. The observed bowel changes were attributed to intravascular thrombosis. Conclusion: Based on our findings, individuals with COVID-19 often develop pulmonary emboli and bowel changes. Multivariate analyses revealed a connection between invasive mechanical ventilation and PE. Our results suggest that patients with severe clinical manifestations of COVID-19 may also have concurrent acute PE. Thus, for these patients, utilizing contrast-enhanced CT scans instead of standard non-contrast CT scans may aid in treatment decision-making.

Noninvasive diagnostic value of urinary mir-663a in pediatric lupus nephritis

Abstract Background and objectives Lupus nephritis (LN) is a severe clinical manifestation seen in individuals with systemic lupus erythematous (SLE). It has a poor long-term prognosis in pediatric patients with high morbidity and mortality rates. MicroRNAs (miRNAs) are noncoding small RNAs that act as epigenetic modulators, regulating gene expression, and modulating the understanding of mechanisms and pathogenesis of human diseases. Depending on bioinformatics analysis, we aimed to investigate urinary expression of miR-663a in LN among SLE children and discriminate between proteinuria of LN versus chronic renal disease without SLE. Methods The urinary miR-663a expression levels were estimated in cellular pellets from 15 SLE patients, 15 SLE and biopsy-proven active LN patients, 15 chronic kidney disease (CKD) patients rather than LN and 15 healthy controls. Results LN patients had significantly higher urinary miR-663a expression levels compared to other groups (p &lt; 0.0001). Urinary miR-663a at a cutoff of 8.61 had a diagnostic value of 93.3% for LN among pediatric SLE with 100% specificity (p &lt; 0.0001). Moreover, miR-663a was upregulated in advanced grades and LN classes V, IV, and III compared to class II. Furthermore, miR-663a was positively correlated with the duration of SLE, activity index, chronicity index, urinary protein, anti-dsDNA, and SLEDAI score, and negatively correlated with serum complement C3 (p &lt; 0.05). Conclusion miR-663a could be related to the pathogenesis of kidney damage in LN; that could provide a specific noninvasive diagnostic and follow -up tool for LN patients.

Serological study of Crimean – Congo haemorrhagic fever in Sheep in Thi – Qar province

Crimean Congo hemorrhagic fever virus (CCHFV) causes a lethal tick – borne zoonotic disease with severe clinical manifestation in humans but does not produce symptomatic disease in wild or domestic animals. It is endemic in a large region of the word. One of the main indicators that the disease is endemic in a region is the presence of antibodies specific to CCHFV in animal populations. The factors contributing to differential outcomes of infection between species are not understood. Serological studies have shown sheep are important to the survival of CCHFV in nature. Nevertheless, need for more studies on this subject in Iraq. Blood samples were taken from 200 sheep of different sex, variable age and physiological status. Only 100 samples used for physiological testes while 186 used for Microbiological test (ELISA) test. The present study was appeared a high level about (144)78.53% of positive carrier sheep while negative samples (42)21.46% in Thi – Qar province which include different regions such as Al-eakihah , Al- rifai and Al- garma region which recorded about 92.85% , 90% and 90 % respectively comparative with another region of thi qar province that appear low level of infected such as Al-fadhliya , Al-tar and Al- manar which recorded about 75%, 50% and 60.71% respectively. The current study focused on and attempted to connect the different physiological states, sex and age with infected animals. The male sex appears ahigh level of infected about 83.92% comparative with female was appeared low level of infected by CCHF virus about 74.61%, while recorded high infected in non – pregnant about 75% comparative with pregnant about 73,80 . Also, the present study was showed ahigh level of infected in age from 5 to nine years about 82.4% comparative with another age ranges which appeared about 71.11, 78.50 %.

Patient-reported outcome measures for lupus nephritis: content validity of LupusQoL and FACIT-Fatigue

BackgroundLupus nephritis (LN), a severe organ manifestation of systemic lupus erythematosus (SLE), significantly impacts health-related quality of life (HRQoL). Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) and Lupus Quality of Life (LupusQoL) have been validated to measure HRQoL in SLE, but not specifically in LN. Patient-reported symptoms of LN are not well-reported. We assessed the content validity and relevance of these measures in evaluating patients with LN and their LN-related experiences.MethodsThis qualitative, interview-based study enrolled patients with LN from three US sites from a larger, retrospective survey study. The interview comprised an open-ended concept elicitation part and a more structured cognitive part. Concept elicitation was used to identify relevant themes describing the patients’ experiences. Patients were asked to describe their LN-related symptoms, the severity and impact of those symptoms and their satisfaction with treatment. A cognitive interview approach evaluated the appropriate understanding of the items, instructions, and response options and asked patients about their understanding of the FACIT-Fatigue or LupusQoL measures, their relevance to the condition, and any aspects of confusion or need for better clarity of the questionnaires. All interviews were recorded and transcribed. The concept elicitation data were coded, while the cognitive interview data were tabulated to present the participants’ responses next to the interview questions to support the evaluation of their understanding of the questionnaire items.ResultsOverall, 10 patients participated in FACIT-Fatigue and another 10 in LupusQoL interviews; 18 patients were female, 10 were Black (self-reported) and 17 were receiving maintenance treatment for LN with stable disease activity. When patients recalled their symptoms, 670 expressions of varying symptoms were reported. All patients described pain, discomfort, and energy-related symptoms. Urinary frequency and non-joint swelling were most frequently attributed to LN rather than SLE. Patients felt the questions asked in the FACIT-Fatigue and LupusQoL surveys were relevant to their LN experience.ConclusionsThe symptoms reported by patients with LN were consistent with symptoms reported by the overall SLE population. However, patients indicated that some symptoms of LN were more profound than symptoms of SLE alone, affecting a broad range of areas of daily life activity and resulting in a higher burden on their HRQoL. FACIT-Fatigue and LupusQoL demonstrated content relevance as meaningful tools for patients with LN. However, further quantitative data collection is needed to ensure that these patient-reported outcome tools demonstrate good measurement properties in an LN population.

Predicting Intra- and Postpartum Hemorrhage through Artificial Intelligence.

Background and Objectives: Intra/postpartum hemorrhage stands as a significant obstetric emergency, ranking among the top five leading causes of maternal mortality. The aim of this study was to assess the predictive performance of four machine learning algorithms for the prediction of postpartum and intrapartum hemorrhage. Materials and Methods: A prospective multicenter study was conducted, involving 203 patients with or without intra/postpartum hemorrhage within the initial 24 h postpartum. The participants were categorized into two groups: those with intra/postpartum hemorrhage (PPH) and those without PPH (control group). The PPH group was further stratified into four classes following the Advanced Trauma Life Support guidelines. Clinical data collected from these patients was included in four machine learning-based algorithms whose predictive performance was assessed. Results: The Naïve Bayes (NB) algorithm exhibited the highest accuracy in predicting PPH, boasting a sensitivity of 96.3% and an accuracy of 98.6%, with a false negative rate of 3.7%. Following closely were the Decision Tree (DT) and Random Forest (RF) algorithms, each achieving sensitivities exceeding 94% with a false negative rate of 5.9%. Regarding severity classification I, the NB and Support Vector Machine (SVM) algorithms demonstrated superior predictive capabilities, achieving a sensitivity of 96.4%, an accuracy of 92.1%, and a false negative rate of 3.6%. The most severe manifestations of HPP were most accurately predicted by the NB algorithm, with a sensitivity of 89.3%, an accuracy of 82.4%, and a false negative rate of 10.7%. Conclusions: The NB algorithm demonstrated the highest accuracy in predicting PPH. A notable discrepancy in algorithm performance was observed between mild and severe forms, with the NB and SVM algorithms displaying superior sensitivity and lower rates of false negatives, particularly for mild forms.

Ifosfamide-Induced Encephalopathy in Relapsed Lymphoma: Report of Two Cases

Objective: Ifosfamide is a chemotherapeutic drug available for various malignancy, including lymphoma. Ifosfamide has adverse effects including myelosuppression, nephrotoxicity, hemorrhagic cystitis, and neurotoxicity. Encephalopathy is a severe manifestation of neurotoxicity due to ifosfamide, with an incidence of 10-40%. This study aimed to report two cases of ifosfamide-induced encephalopathy. Case: This case studies reported two relapsed lymphoma patients with almost similar characteristics who received ifosfamide chemotherapy. The first case of 48-year-old woman with relapsed High-Grade B-cell lymphoma stage IIIBE while the second case of 38-year-old woman with relapsed non-hodgkin lymphoma.Results: The first case showed a good outcome with improvement in consciousness 48 hours after stopping ifosfamide and thiamine, while the second case experienced tumor lysis syndrome, leading to the death of the patient.Conclusion: Mechanism of ifosfamide-induced encephalopathy remains unclear, with the hypothesis from the neurotoxic effects of the resultant metabolite chloracetyldehide. Radiology examination of the brain and electroencephalography is required to rule out other differential diagnoses. Early recognition of adverse effects, followed by immediate discontinuation of ifosfamide, administration of therapy, such as methylene blue and/or thiamine, and supportive treatment usually produced good outcomes.

Prevalence, duration, and factors influencing post-COVID conditions among patients at several public hospitals, Alexandria governorate, Egypt 2022–2023

BackgroundPost-COVID conditions (PCC), characterized by persistent symptoms following acute infection, represent an emerging chronic illness that potentially affects millions of people worldwide. SARS-CoV-2 infection has resulted in a PCC incidence ranging from 10 to 30 % in non-hospitalized individuals to 50–70 % in hospitalized patients. Most PCC patients experience mild symptoms, while a minority report severe manifestations. We aimed to estimate the prevalence of PCC among COVID-19 patients who attended three public hospitals in Alexandria, Egypt between June 2022 and February 2023, and to investigate its risk factors. MethodsAll COVID-19-confirmed patients aged >18 years attended the selected hospitals, and their household contacts were contacted. Data were collected through telephone interviews using a questionnaire adapted from World Health Organization (WHO) and Penn Medicine tools, covering demographics, COVID-19 history, and PCC symptoms. PCC was defined as symptoms starting three months after the post-acute infection and lasting for at least two months beyond. Statistical analyses employed descriptive statistics, chi-square tests, and a logistic regression model, with a significance level of p < 0.05. ResultsA total of 1546 patients were enrolled. Their mean age was 39.7 ± 15.9 years, 46.0 % were males, and 13.9 % had comorbidities. Of them, 760 patients (49.2 %) reported PCC symptoms including, 52.6 % seen at outpatients, 26.7 % were admitted, and 0.5 % required admission to ICU. PCC symptoms included shortness of breath (94.2 %), mood changes (13.9 %), cough (13.0 %), and fatigue (8.8 %). PCC was associated with older age, hospitalization during acute COVID-19, comorbidities including asthma, hypertension, and diabetes, as well as treatment with different COVID-19 medications. Logistic regression shows that asthma, male gender, and treatment with medicines at the hospital remained significant in the model (ORs: 6.85, 0.36, and 0.88, p < 0.001). ConclusionThis study sheds light on PCC's prevalence and influencing factors following infection in Alexandria, Egypt. Common PCC symptoms included difficulty in breathing, fatigue, and psychological manifestations. The findings emphasize the critical need for early intervention and targeted management strategies, especially for high-risk groups such as asthma patients, to alleviate the long-term health consequences of COVID-19. Study results could guide the prevention of PCC e.g., through vaccination, management of long-term sequelae of PCC e.g., rehabilitation, and psychological support initiatives.

A Simple and Rapid Colorimetric Method for Methanol Determination Using Sodium Nitroprusside

Introduction: Methanol (CH3OH) exposure can be highly toxic to humans, resulting in severe clinical manifestations and even deaths if left untreated. Therefore, it is vital to estimate the amounts of methanol quickly and accurately to avoid its adverse health impacts. The main goal of the current study was to develop a simple, fast, reliable, and cost-effective colorimetric method for determining methanol amounts in some alcoholic and non-alcoholic samples. Materials and Methods: A sodium nitroprusside-based colorimetric method was established to detect methanol in hand sanitizers, alcoholic beverages, and herbal distillations. A gas chromatography-mass spectrometry apparatus was applied to evaluate the efficacy of the Kit. Results: The naked eye saw the color change in the presence of methanol. The established method revealed a good sensitivity (0.077%) and accuracy for methanol determination in different samples. Besides, this colorimetric method was precise, with intra- and inter-assay coefficients of variations less than 10%. Notably, the recovery percentages were 96.5% to 108%, indicating the acceptable accuracy of the studied method. The quantitative detection of methanol was finally validated by comparing it with gas chromatography-mass spectrometry results. Conclusions: This colorimetric method has great potential for methanol detection due to advantages such as good sensitivity, acceptable accuracy, and fast response time.

Protective role of antibodies in enteric virus infections: Lessons from primary and secondary immune deficiencies.

Enteric viruses are the main cause of acute gastroenteritis worldwide with a significant morbidity and mortality, especially among children and aged adults. Some enteric viruses also cause disseminated infections and severe neurological manifestations such as poliomyelitis. Protective immunity against these viruses is not well understood in humans, with most knowledge coming from animal models, although the development of poliovirus and rotavirus vaccines has extended our knowledge. In a classical view, innate immunity involves the recognition of foreign DNA or RNA by pathogen recognition receptors leading to the production of interferons and other inflammatory cytokines. Antigen uptake and presentation to T cells and B cells then activate adaptive immunity and, in the case of the mucosal immunity, induce the secretion of dimeric IgA, the more potent immunoglobulins in viral neutralization. The study of Inborn errors of immunity (IEIs) offers a natural opportunity to study nonredundant immunity toward pathogens. In the case of enteric viruses, patients with a defective production of antibodies are at risk of developing neurological complications. Moreover, a recent description of patients with low or absent antibody production with protracted enteric viral infections associated with hepatitis reinforces the prominent role of B cells and immunoglobulins in the control of enteric virus.

Characterization of Endothelial Cell Subclusters in Localized Scleroderma Skin with Single-Cell RNA Sequencing Identifies NOTCH Signaling Pathway

Localized scleroderma (LS) is an autoimmune disease characterized by inflammation and fibrosis, leading to severe cutaneous manifestations such as skin hardening, tightness, discoloration, and other textural changes that may result in disability. While LS shares similar histopathologic features and immune-fibroblast interactions with systemic sclerosis (SSc), its molecular mechanisms remain understudied. Endothelial cells (EC) are known to play a crucial role in SSc but have not been investigated in LS. Single-cell RNA sequencing (scRNA-seq) now allows for detailed examination of this cell type in the primary organ of interest for scleroderma, the skin. In this study, we analyzed skin-isolated cells from 27 LS patients (pediatric and adult) and 17 healthy controls using scRNA-seq. Given the known role of EC damage as an initial event in SSc and the histologic and clinical skin similarities to LS, we focused primarily on endothelial cells. Our analysis identified eight endothelial subclusters within the dataset, encompassing both disease and healthy samples. Interaction analysis revealed that signaling from diseased endothelial cells was predicted to promote fibrosis through SELE interaction with FGFBP1 and other target genes. We also observed high levels of JAG in arterial endothelial cells and NOTCH in capillary endothelial cells, indicating the activation of a signaling pathway potentially responsible for epidermal abnormalities and contributing to LS pathogenesis. In summary, our scRNA-seq analysis identified potential disease-propagating endothelial cell clusters with upregulated pathways in LS skin, highlighting their importance in disease progression.

Severe neurological and ocular manifestations in paediatric patients with toxoplasmosis. Case-series study with review of the current literature

Toxoplasmosis, both congenital and postnatally acquired, is a parasitic disease caused by infection with the protozoan Toxoplasma gondii. The most serious manifestation of this disease is congenital toxoplasmosis, resulting from transplacental infection of the foetus during pregnancy. Retinochoroiditis, intracranial calcifications, and hydrocephalus are considered the classic triad of congenital toxoplasmosis. This article describes four cases of severe neurologic and ocular manifestations in paediatric patients diagnosed with toxoplasmosis. The main aim was to examine the nature of clinical presentation as well as to emphasise the necessity of properly administered antiparasitic therapy and underline the importance of prenatal screening to reduce the risk of congenital transmission to the foetus.

Pregnancy Among Reported Lyme Disease Cases-United States, 1992-2019.

Lyme disease (LD), the most common vector-borne disease in the United States, typically presents with a localised erythema migrans rash (EM). Left untreated, infection can disseminate to cause severe heart, joint or nervous system manifestations. Summaries of LD surveillance data have been published previously but did not include the frequency, demographic or clinical characteristics of LD cases during pregnancy. We summarised confirmed and probable LD cases by pregnancy status as reported to the U.S. Centers for Disease Control and Prevention during 1992-2019. We defined an LD case during pregnancy as one with (1) female sex, (2) age 14-49 years and (3) positive pregnancy indication. We evaluated the frequency, seasonality, age distribution, race and ethnicity, geographic distribution and clinical manifestations of LD cases during pregnancy and cases among non-pregnant females. We compared proportions using chi-squared tests. Among 698,876 reported LD cases, 112,002 (16%) were confirmed or probable cases among females aged 14-49 years; 32,301 (29%) were specifically reported as non-pregnant and 643 (0.6%) (568 confirmed and 75 probable cases) reported as pregnant. Illness onset peaked in June among LD cases during pregnancy, but in July for cases among non-pregnant females. A higher proportion of confirmed LD cases during pregnancy had only EM rash than did cases among non-pregnant females (66% vs. 60%, p = 0.019). LD cases during pregnancy are rare. Compared to non-pregnant females, cases among pregnant females more commonly involve early clinical manifestations. These patterns could suggest earlier detection or more complete reporting of LD cases during pregnancy than their non-pregnant counterparts. Earlier detection could be due to frequent contact with healthcare or increased self-advocacy during pregnancy. Prompt antimicrobial treatment is critical for preventing severe disease and reducing risk of adverse pregnancy or birth outcomes.