Clinical Course Research Articles

Proximal-type epithelioid sarcoma: A new case report

Epithelioid sarcoma (ES) is a rare high-grade soft tissue sarcoma, first described by Enzinger in 1970, classically presenting as a subcutaneous or deep dermal mass in the distal extremities of adolescents and young adults. In 1997, Guillou et al. described the proximal-type epithelioid sarcoma, which is found mostly in the pelvic, perineal regions, and genital tracts of young to middle-aged adults. Epithelioid sarcoma is characterized by a proliferation of epithelioid-like cells with rhabdoid features and the absence of a granuloma-like pattern. We present, in this paper, a case of proximal-type epithelioid sarcoma of abdominal wall, with an aggressive clinical course, including distant metastasis and death one month after diagnosis. In this particular case, the location is infrequent, and it had not previously been described.

Regular use of fish oil supplements and course of cardiovascular diseases: prospective cohort study

ObjectiveTo examine the effects of fish oil supplements on the clinical course of cardiovascular disease, from a healthy state to atrial fibrillation, major adverse cardiovascular events, and subsequently death.DesignProspective cohort...

Retinal focal nodular gliosis have varied clinical courses requiring tailored management: a case series

Purpose: Retinal focal nodular gliosis (FNG), also known as vasoproliferative tumors (VPTs), are rare, benign vascular tumors associated with exudation with no current consensus on management. Herein, we describe the varied clinical course and management of three patients with retinal focal nodular gliosis, one of whom is associated with retinitis pigmentosa. Observations: Case 1 is a 76-year-old female who presented with reduced vision and distortion secondary to a vitreous hemorrhage and epiretinal membrane (ERM) as complications of a known small peripheral retinal focal nodular gliosis. She underwent vitrectomy for the hemorrhage to relieve vascular traction and the ERM peel and the tumor was kept under observation. Case 2 is a 24-year-old female with genetically uncharacterized retinitis pigmentosa-like phenotype who presented with gradual loss of central vision in one eye due to cystoid macular oedema (CMO). She was found to have two peripheral retinal areas of focal nodular gliosis located inferonasally. Tumors were treated with cryotherapy and adjuvant intraocular steroid implant to control the CMO. Case 3 is a 28-year-old female with retinitis pigmentosa secondary to genetically confirmed variant in CRB1 gene who presented with intractable right eye cystoid macular oedema and localized inferior serous retinal detachment secondary to a large inferotemporal focal nodular gliosis. Her left eye has no light perception vision due to previous extensive serous retinal detachment and anterior segment ischemia. The right eye tumor was managed with multiple rounds of cryotherapy and laser therapy to control the serous detachment. Despite this, the condition progressed and was ultimately treated with plaque brachytherapy. Unfortunately, this resulted in an extensive retinal inflammation causing annular tractional retinal detachment which was treated with combined pars plana vitrectomy and scleral buckle. Conclusions: We characterized the retinal phenotype of three patients with retinal focal nodular gliosis (vasoproliferative tumors) and found them to have varied clinical courses requiring tailored surgical management. The case associated with retinitis pigmentosa had a known pathogenic variant in Crumbs homolog-1 (CRB1) gene affecting retinal structure and exhibited a more severe clinical course. It is therefore important for patients with retinal dystrophies to undergo thorough peripheral examinations and detect FNG early as they may require prompt, aggressive treatment.

THE IMPACT OF VACCINATION STATUS ON THE CLINICAL CHARACTERISTICS OF MEASLES COURSE

Measles is a dangerous and highly contagious viral disease with a tendency to spread rapidly. The incidence of measles is cyclical with outbreaks occurring every 5-6 years and is directly related to the level of vaccination against the disease. Measles can become severe clinical course and have serious, sometimes fatal consequences. The purpose of the study is to compare the clinical course of measles depending on the vaccination status of patients. We analysed medical records of 218 patients aged 18 to 55 years who were inpatients with a diagnosis of measles at the Poltava Regional Clinical Infectious Diseases Hospital. The clinical features of measles were compared based on vaccine status using descriptive statistics methods in accordance with the analysis requirements. Comparison of the clinical course of the disease depending on vaccination status did not reveal a statistically significant difference in clinical symptoms between the groups of vaccinated and unvaccinated individuals. However, in the group of unvaccinated patients, a severe course of measles was significantly more often observed compared to those who were vaccinated (p = 0.003). The incidence of complications was studied and found to be lower in vaccinated individuals than in non-immune patients (p = 0.051), specifically pneumonia (p = 0.006). No cases of complications such as measles encephalitis and enterocolitis were recorded among vaccinated individuals. Thus, the course of the disease was characterised by typical clinical signs with a predominance of intoxication syndrome, the appearance of a typical rash, its stages, the presence of catarrhal and, less often, intestinal syndromes. It was found that vaccinated individuals had significantly less frequent severe measles, and the incidence of complications, including pneumonia, was was significantly lower than in unvaccinated patients.

The quality of reporting in case reports of permanent neonatal diabetes mellitus: a cross-sectional study

BackgroundAlthough randomized trials and systematic reviews provide the best evidence to guide medical practice, many permanent neonatal diabetes mellitus (PNDM) studies have been published as case reports. However, the quality of these studies has not been assessed. The purpose of this study was to assess the extent to which the current case reports for PNDM comply with the Case Report (CARE) guidelines and to explore variables associated with the reporting.MethodSix English and four Chinese databases were searched from their inception to December 2022 for PNDM case reports. The 23 items CARE checklist was used to measure reporting quality. Primary outcome was the adherence rate of each CARE item and second outcome was total reporting score for each included PNDM case report. Linear and logistic regression analyses were used to examine the connection between five pre-specified predictor variables and the reporting quality. The predictor variables were impact factor of the published journal (<3.4 vs. ≥3.4, categorized according to the median), funding (yes vs. no), language (English vs. other language), published journal type (general vs. special) and year of publication (>2013 vs. ≤ 2013).ResultIn total, 105 PNDM case reports were included in this study. None of the 105 PNDM case reports fulfilled all 23 items of the CARE checklist. The response rate of 11 items were under 50%, including prognostic characteristics presentation (0%), patient perspective interpretation (0%), diagnostic challenges statement (2.9%), clinical course summary (21.0%), diagnostic reasoning statement (22.9%), title identification (24.8%), case presentation (33.3%), disease history description (34.3%), strengths and limitations explanation (41.0%), informed consent statement (45.7%), and lesson elucidation (47.6%). This study identified that the PNDM case reports published in higher impact factor journals were statistically associated with a higher reporting quality.ConclusionThe reporting of case reports for PNDM is generally poor. As a result, this information may be misleading to providers, and the clinical applications may be detrimental to patient care. To improve reporting quality, journals should encourage strict adherence to the CARE guidelines.

False-positive Findings of Large Vessel Vasculitis on FDG-PET in Patients Treated With Immune Checkpoint Inhibitors.

Fluorine-18 fluorodeoxygluocose positron emission tomography (FDG-PET) is increasingly used in the evaluation of response to immune checkpoint inhibitor (ICI) therapy. Incidental findings of increased vessel wall uptake may prompt the concern for ICI-induced large vessel vasculitis (LVV). Precise radiographic and clinical evaluation is required to determine if this represents true vasculitis, as use of immune suppression and ICI discontinuation can have significant impacts on patient outcomes. We performed a retrospective case analysis of 4 consecutive patients referred to 2 rheumatology clinics treated with ICI with incidental findings of LVV on FDG-PET, reviewing their clinical course and radiographic findings. All 4 cases had FDG-PET scans for routine oncology indications and had no associated clinical features of LVV. One patient was treated with corticosteroids and no patients developed any clinical evidence of vasculitis during a mean follow-up period of 17 months (range: 7-33mo). All FDG-PET images reporting LVV underwent a standardized analysis to identify any technical issues or concerns with interpretation. In review of imaging, 3 of the cases may have been due to delayed tracer to scan interval leading to misinterpretation of vascular uptake as suspected LVV. Recognition of technical pitfalls in FDG-PET interpretation is crucial to inform the need for immunosuppression and the safety of continued ICI therapy.

Lipoprotein glomerulopathy with markedly increased arterial stiffness successfully treated with a combination of fenofibrate and losartan: a case report

BackgroundLipoprotein glomerulopathy (LPG) is a apolipoprotein E (ApoE)-related glomerular disease and has been associated with type III hyperlipidemia. Without appropriate treatment, chronic kidney disease (CKD) caused by LPG progresses, and approximately half of the patients develop end-stage kidney disease within 1–27 years of disease onset. However, few studies have highlighted the clinical course of cardiovascular diseases (CVDs) in patients with LPG. Herein, we report the first case of LPG in which the CVD risk was assessed using arterial stiffness.Case presentationA 32-year-old Japanese man was referred to our hospital due to persistent proteinuria. Kidney biopsy showed markedly dilated capillary lumens containing pale-stained thrombi, which stained positively with Oil Red O. Electron microscopy revealed the presence of thrombi in the capillary lumen with low electron density and vacuoles of various sizes in part of the thrombi. Toluidine blue and Sudan IV stains were used to stain the thin sections of Epon-embedded tissue samples for electron microscopy. Sudan IV-positive droplets were observed in the capillary lumens, vascular walls, and cytoplasm of tubular cells. Increased serum ApoE concentration was observed. Liquid chromatography-tandem mass spectrometry of laser-microdissected glomeruli from paraffin sections revealed an increase in ApoE. Direct deoxyribonucleic acid sequencing of ApoE revealed a heterozygous ApoE Sendai mutation (Arg145Pro). The patient was finally diagnosed with LPG with heterozygosity for ApoE-Sendai mutation (Arg145Pro). Notably, at the time of diagnosis, he had markedly increased arterial stiffness for his age. Arterial stiffness was measured using brachial-ankle pulse wave velocity (baPWV), which was equivalent to that of a 56-year-old man. After three months of treatment with fenofibrate and losartan, a significant reduction in proteinuria was achieved along with an improvement in baPWV. Furthermore, these effects were maintained despite the lack of decrease in serum ApoE levels.ConclusionHerein, we report the case of a patient with LPG with markedly increased arterial stiffness at the time of diagnosis, in whom combination therapy with fenofibrate and losartan successfully improved proteinuria and arterial stiffness. To the best of our knowledge, this is the first case report of LPG in which CVD risk was assessed using arterial stiffness.

INDEX ASSESSMENT OF PERIODONTAL TISSUES AND DETERMINATION OF TREATMENT NEEDS IN PATIENTS WITH CHRONIC RHEUMATIC HEART DISEASE

This study addresses the pressing scientific and practical issue in modern dentistry: enhancing dental care effectiveness for patients with chronic rheumatic heart disease. The purpose of this research is to comprehensively assess the condition of tooth-supporting tissues and quantify inflammatory phenomena in periodontal tissues among patients with chronic rheumatic heart disease, as well as to determine the necessary extent of periodontal care based on periodontal indices. Participants and methods. The periodontal tissues of 719 patients with chronic rheumatic heart disease from the Rheumatology Department of Lviv Regional Clinical Hospital, along with 290 clinically healthy individuals in the comparison group, were examined. To evaluate the clinical course of dystrophic-inflammatory periodontal diseases in patients with chronic rheumatic heart disease, we examined 267 individuals in the main group who had generalized periodontitis, categorized as follows: 42 patients with initial stage (I degree), 115 with moderate (II degree), and 110 with severe (III degree) periodontitis. The comparison group comprised 70 patients diagnosed with generalized periodontitis, among them, 21 had initial-stage disease, 29 had moderate-stage disease, and 20 had severe-stage disease. During the analysis, the oral hygiene was assessed by applying hygienic indices by J.C. Green and J.R. Vermillion (OHI-S, 1964) and Fedorov-Volodkina. The Muhlemann and Son index was used to objectively measure gingival papillary bleeding (RVI); the papillary-marginal-alveolar index (PMA) in the Parma modification, in combination with the Schiller-Pysarev test (1989), was employed to evaluate gingival inflammation. The periodontal index (PI) by A.L. Russel (1956) was used to assess the state of periodontal tissues, and pathological changes were recorded using the periodontal screening PSR test. Results were scored, and based on established criteria and scores, the need for treatment and its extent were determined. Results and discussion. According to the results of dental examinations in patients with chronic rheumatic heart disease, a high prevalence of periodontal diseases was found, reaching 92.49%. This was 13.18% higher compared to the prevalence in the control group. Dystrophic-inflammatory conditions with advanced severity levels were predominant, as evidenced by the index indicators. In chronic rheumatic heart disease patients, the average periodontal index was 6.11±0.10, compared to 4.14±0.19 in clinically healthy individuals (p &lt; 0.05). Moreover, a higher lesion of periodontal tissues was observed in younger age groups. As the duration of rheumatic disease increased, the frequency of detecting generalized periodontitis also increased, with this condition being diagnosed in all subjects with a 10-year history of rheumatic disease. Conclusion. The Analysis of the research data on the condition of periodontal tissues, along with objective index assessments, reveals the following: periodontal diseases are more prevalent in individuals with chronic rheumatic heart disease, particularly affecting younger age groups. The severity and progression of these diseases are influenced by the course of the underlying condition. This underscores the presence of pathogenetic conditions that contribute to the rapid progression of the dystrophic-inflammatory process in periodontal tissues. It also emphasizes the importance of providing specialized periodontal care to patients with chronic rheumatic heart disease, with the level of care directly linked to the course and duration of the systemic disease.

Role of extracorporeal membrane oxygenation in pediatric myocarditis

ABSTRACT Fulminant myocarditis in children is rare, but it has the potential for high morbidity and mortality. In this report, we review articles demonstrating the role of venoarterial extracorporeal membrane oxygenation (VA-ECMO) in the fulminant myocarditis, and describe the clinical course of a healthy 11-year-old girl who rapidly deteriorated into cardiogenic shock. The patient was weaned from mechanical ventilation on day 7 and she was discharged from the ICU on day 12. VA-ECMO is considered as a life-saving therapy in patients with hemodynamic instability prior to recovery or other escalation therapy.

DNA methylation profile and expression of the phyllagrin gene in patients with atopic dermatitis: case-control study

Background. Atopic dermatitis (AD) is one of the most common inflammatory skin diseases, affecting up to 20.0% of children and 2.0–8.0% of adults worldwide. Patients with atopic dermatitis usually have dry skin and itching, they are at higher risk of developing asthma, as well as allergic rhinitis. Features of the clinical course of AD are associated with both interaction of genes and influence of environmental factors. Studying epigenetic mechanisms could provide understanding of the most likely mechanisms by which environmental factors influence gene expression and contribute to the development of AD. The aim of the study is to conduct a comprehensive molecular genetic analysis (assessment of the level of global DNA methylation and expression of the filaggrin gene (FLG) in patients with moderate to severe AD. Material and methods: The case-control study was conducted from January 2022, through June 2022. A total of 32 patients with AD and 6 healthy volunteers were recruited. The level of global DNA methylation in the blood of patients with AD and healthy individuals was assessed. The FLG expression was measured by polymerase chain reaction in the leukocyte fraction of blood. A three-stage cycle is used during PCR. To determine the expression level of the FLG gene, total RNA was isolated, followed by a reverse transcription, amplification, and detection reaction. Results. A hypermethylation of the genome in patients with AD is 2.3 times higher than the methylation of genome in controls (p = 0.003),it was also found that the expression level of the FLG gene (exon 3, position 7–8, and exon 1) in the leukocyte fraction of blood in patients with AD did not significantly differ from the control group (p = 0.41). Conclusion. The current study found that the epigenome of AD patients differs from healthy individuals. The study of pathogenetic mechanisms is the basis for the development of new methods of targeted therapy for this socially significant dermatosis.

Clinical Course and Outcomes of Autoimmune Versus Non-Autoimmune Surgically Induced Scleral Necrosis: A Multicentric Comparative Study

ABSTRACT Background To analyze the clinical course and outcomes of autoimmune vs. non-autoimmune surgically induced scleral necrosis (SISN). Methods Multicentric, retrospective, comparative cohort study. Eighty-two eyes of 70 patients with SISN were classified according to pathogenic mechanism into autoimmune vs. non-autoimmune. Main outcome measures included necrosis onset, type of surgery, associated systemic disease, visual acuity, and treatment were analysed in patients followed for ≥ 6 months. Results Forty-six (65.7%) patients were women, and the median age was 66 (range: 24–90) years. Most patients (82.9%) had unilateral disease. The median time between surgery and SISN onset was 58 (1–480) months. Thirty-one (37.8%) eyes were classified as autoimmune, and 51 (62.2%) as non-autoimmune SISN. Autoimmune SISN was associated with a shorter time between the surgical procedure and SISN onset than non-autoimmune cases (median of 26 vs. 60 months, p = 0.024). Also, autoimmune SISN was associated with cataract extraction (93.5% vs. 25.5%, p < 0.001), severe scleral inflammation (58.1% vs. 17.6%, p < 0.001), and higher incidence of ocular complications (67.7% vs. 33.3%, p = 0.002) than non-autoimmune cases. Remission was achieved with medical management alone in 44 (86.3%) eyes from the non-autoimmune and in 27 (87.1%) from the autoimmune group (p = 0.916). Surgical management was required in 11 (13.4%) eyes, including two requiring enucleations due to scleral perforation and phthisis bulbi. Conclusions Eyes with autoimmune SISN had a higher rate of cataract surgery, severe scleral inflammation, and ocular complications. Early SISN diagnosis and appropriate management, based on clinical features and pathogenic mechanisms, are critical to avoid sight-threatening complications.

Complex decision making in a patient with lung cancer with incidentally found fast-growing atrial mass

Atrial myxomas are typically found in the left atrium and are the most common among overall rare cardiac tumors. Herein, we describe the clinical course of a 72-year-old female with non-small cell lung adenocarcinoma found to have an atrial mass during an imaging for evaluation for lung cancer progression. Differentiating between distinct types of masses can pose a challenge to the treatment team especially in the setting of exiting malignancy. This case demonstrates the complex decision making involved in the diagnosis, and timing of intervention to remove atrial mass in patients with frailty and a fast-growing cardiac mass.

Retrospectively diagnosed autoimmune VWF deficiency in a patient with repeated hemorrhagic events after two common colds.

Autoimmune von Willebrand factor (VWF) deficiency (AiVWFD) caused by anti-VWF autoantibodies is a rare bleeding disorder, whereas "non-immune" acquired von Willebrand syndrome (AVWS) caused by other etiologies is more common. Therefore, only 40 patients with AiVWFD have been identified in Japan through an ongoing nationwide survey on autoimmune coagulation factor deficiencies. This may be due to the inability to efficiently detect anti-VWF antibodies, as anti-VWF antibody testing is not routine. An 80-year-old Japanese woman developed AVWS and experienced bleeding after two separate common colds. She took the same cold medicine each time and recovered spontaneously after discontinuation of the medicine. Severe VWF deficiency normalized each time. Initial immunological tests did not detect anti-VWF autoantibodies, and thus a diagnosis of "non-immune" AVWS of unknown origin was made. However, after 6years, new ELISA assays using purified VWF proteins detected free anti-VWF autoantibodies, which led to a retrospective diagnosis of AiVWFD. It is probable that the cold medicine (and/or cold virus infection) induced the autoantibodies, as the recurrence and normalization of the same coagulation abnormality and the clinical course (including drug administration and discontinuation) were completely synchronized. If AiVWFD is suspected, highly sensitive autoantibody tests should be performed.

Clinical and functional characterization of a novel KCNJ11 (c.101G > A, p.R34H) mutation associated with maturity-onset diabetes mellitus of the young type 13.

This study aimed to describe the clinical features, diagnostic and therapeutic course of a patient with MODY13 caused by KCNJ11 (c.101G > A, p.R34H) and how it contributes to the pathogenesis of MODY13, and to explore new therapeutic targets. Whole-exome sequencing was used to screen prediagnosed individuals and family members with clinically suspected KCNJ11 mutations. Real-time fluorescence quantitative PCR, western blotting, thallium flux of potassium channels, glucose-stimulated insulin secretion (GSIS), and immunofluorescence assays were used to analyze the regulation of insulin secretion by the KCNJ11 mutant in MIN6 cells. Daily blood glucose levels were continuously monitored for 14 days in the proband using the ambulatory blood glucose meter (SIBIONICS). Mutation screening of the entire exon of the gene identified a heterozygous KCNJ11 (c.101G > A, p.R34H) mutation in the proband and his mother. Cell-based GSIS assays after transfection of MIN6 using wild-type and mutant plasmids revealed that this mutation impaired insulin secretory function. Furthermore, we found that this impaired secretory function is associated with reduced functional activity of the mutant KCNJ11 protein and reduced expression of the insulin secretion-associated exocytosis proteins STXBP1 and SNAP25. For the first time, we revealed the pathogenic mechanism of KCNJ11 (c.101G > A, p.R34H) associated with MODY13. This mutant can cause alterations in KATP channel activity, reduce sensitivity to glucose stimulation, and impair pancreatic β-cell secretory function by downregulating insulin secretion-associated exocytosis proteins. Therefore, oral sulfonylurea drugs can lower blood glucose levels through pro-insulinotropic effects and are more favorable for patients with this mutation.

Effects of Metreleptin in Patients with Generalized Lipodystrophy Before vs After the Onset of Severe Metabolic Disease.

Leptin replacement therapy with metreleptin improves metabolic abnormalities in patients with generalized lipodystrophy (GLD). Determine how timing of metreleptin initiation in the clinical course of GLD affects long-term metabolic health. Retrospective analysis of patients ≥ 6 months old with congenital (n=47) or acquired (n=16) GLD treated with metreleptin at the National Institutes of Health since 2001. Least squares means (LSM) for HbA1c, insulin area under the curve (AUC) from oral glucose tolerance tests, triglycerides, urine protein excretion, platelets, transaminases, and aspartate aminotransferase (AST) to Platelet Ratio Index (APRI) for early and late treatment groups, defined by baseline metabolic health, were analyzed during median 72 (24, 108) months follow-up. Compared to late groups, early groups based on metabolic status had higher mean±SEM insulin AUC (20831±1 vs 11948±1), lower HbA1c (5.3±0.3 vs 6.8±0.3%), triglycerides (101±1 vs 193±1 mg/dL), urine protein excretion (85±1.5 vs 404±1.4 mg/24 hr), ALT (30±1 vs 53±1 U/L), AST (23±1 vs 40±1 U/L), and APRI (0.22±1.3 vs 0.78±1.3), and higher platelets (257±24 vs 152±28 K/µL) during follow-up (P<0.05). Compared to patients ≥6 years old at baseline, patients <6 years had lower HbA1c (4.5±0.5 vs 6.4±0.2%) and higher AST (40±1vs 23±1 U/L) during follow (P<0.05). Patients with GLD who initiated metreleptin before the onset of severe metabolic complications had better long-term control of diabetes, proteinuria, and hypertriglyceridemia. Early treatment may also result is less severe progression of liver fibrosis, but further histological studies are needed to determine the effects of metreleptin therapy on liver disease.

Endolymphatic sac tumor: An urgent case presenting acute intracranial hypertension successfully treated with suboccipital decompressive craniectomy – 8 years of follow-up

Background: Endolymphatic sac tumor (ELST) is a rare lesion. It may be sporadically or associated with Von Hippel-Lindau syndrome. Progressive audiovestibular symptoms characterize the typical clinical presentation. Here, we report a unique case of ELST with acute intracranial hypertension (IH) due to tumor compression, successfully treated with an urgent suboccipital decompressive craniectomy (SDC). Case Description: A 33-year-old woman previously underwent a biopsy and ventriculoperitoneal shunt. The histopathological finding revealed an ELST. One year later, she developed headache, vomiting, and somnolence due to brainstem compression. An urgent SDC was performed. One month later, preoperative endovascular embolization and partial tumor resection were carried out. After 6 months adjuvant radiotherapy (RT) therapy was administered. She has been under follow-up for 8 years since the last surgical procedure, and the tumor remains stable. Conclusion: ELST generally has a progressive clinical course. This is a unique case with acute IH due to tumor compression. The tumor’s high vascularity and the unavailability of endovascular embolization precluded its resection. SDC was an alternative approach. The final treatment included tumor embolization, surgical resection, and RT. No progression was observed for 8 years after the last procedure, and long-term follow-up is warranted.

A study on the prevalence and prognosis of progressive pulmonary fibrosis: A retrospective observational study.

Interstitial lung disease (ILD) encompasses a heterogeneous group of more than 200 diffuse parenchymal lung diseases with various clinical courses. Disease progression is one of the most important prognostic factors, and, the definition of progressive pulmonary fibrosis (PPF) has recently been established. This study aimed to estimate the prevalence, risk factors, and prognosis of PPF among patients with non-idiopathic pulmonary fibrosis (IPF) in real-world practice. A total of 215 patients were retrospectively analyzed between January 2010 and June 2023 at the Haeundae Paik Hospital in the Republic of Korea. According to the criteria proposed in 2022 by Raghu et al, PPF defined as a condition that satisfies 2 or more of the following in the past year: worsening of respiratory symptoms, physiological evidence of disease progression, and radiological evidence of disease progression. The median age of the subjects was 67 years and 63.7% were female. A total of 40% was diagnosed with PPF and connective tissue disease-associated ILD (52.3%) was the most common type, followed by nonspecific interstitial pneumonitis (NSIP) (25.6%) and cryptogenic organizing pneumonitis (16.3%). In multivariate logistic regression for predicting PPF, both the use of steroids and immunosuppressants (OR: 2.57, 95% CI: 1.41-4.67, P = .002) and home oxygen use (OR: 25.17, 95% CI: 3.21-197.24, P = .002) were independent risk factors. During the follow-up period, the mortality rate was significantly higher in the PPF group than in the non-PPF group (24.4% vs 2.3%, P < .001). In the survival analysis using the Cox proportional hazard regression model, disease progression, older age and lower forced vital capacity (FVC) were independent risk factors for mortality. Our study demonstrated that the prevalence of PPF was 40%. Concomitant therapy of steroids with an immunosuppressants and home oxygen use are risk factors for PPF. PPF itself was significantly associated with high mortality rates. Risk factors for mortality were disease progression, older age, and lower FVC.

Extracorporeal Membrane Oxygenation: Rescue Therapy in Pediatric Bupropion Cardiotoxicity

Abstract Objective Our objective was to describe clinical characteristics and course of pediatric bupropion ingestions requiring extracorporeal membrane oxygenation (ECMO) life support. Desgin The study included a retrospective cohort of patients ≤18 years of age reported to a regional poison control (PC) system covering three states in the upper Midwest United States. All bupropion exposures ≤18 years of age, coded as receiving ECMO to treat toxicity, were included. Clinical presentation and management including ECMO are presented as descriptive statistics. Results During the study period, 4,951 bupropion exposures were reported; 1,145 (23.1%) were children. Nine patients were coded as undergoing ECMO; four (44.4%) were ≤18 years of age (median 16, range 14–17). All were treated with venoarterial ECMO. The median time from ingestion to presentation was 2.25 hours (range: 1–3.5). Median first systolic blood pressure and pulse were 100 mm Hg (range: 70–124) and 119.5 (range: 70–175). The median time from ingestion to ECMO was 17.63 hours (range: 7.25–33.75); median number of vasopressors was 2.5 (range: 2–3). All experienced multiple seizures, ventricular dysrhythmias, and hypotension. Three of four sustained cardiac arrest. All but one required transfer to an ECMO-capable facility for definitive care. Three patients survived with full neurologic recovery; one died. Conclusion Pediatric bupropion cases requiring ECMO were rare in this study. Time to initiation and duration of EMCO suggest that the variable onset of hemodynamic instability may delay ECMO initiation. It is incumbent on PCs and medical toxicologists to educate prescribers and pediatricians about bupropion's potential lethality and to consider early transfer to an ECMO center.

EPIDEMIOLOGICAL FRAMEWORK OF MYOCARDITIS DURING SARS–COV–2 PANDEMIC AND VACCINATION CAMPAIGN

Abstract Rationale Myocarditis is an inflammatory condition of cardiomyocytes whose clinical course can be heterogeneous. Etiologies include infections (mostly viral), drugs or toxic exposures or auto–immunity, while few cases have been reported in association with vaccines (following, mainly, attenuated smallpox vaccine). Estimated prevalence is 2–22 cases/100000 people/year, with greater frequency in males aged 30–40. Since SARS–CoV–2 outbreak and vaccination campaigns there is growing interest in their association with myo–pericardial inflammatory conditions, with incidence reports of 1–5/100.000 and 1–5/1.000.000 respectively among vaccinated and unvaccinated subjects (as part of COVID–19) and relatively higher incidence in males after second (mRNA) vaccine administration. Study Design and Objective We designed this observational registry and included patients with CMR–confirmed myocarditis diagnosis admitted to Maggiore Hospital in Bologna from March 2017 to April 2023. Primary goal was to conduct an epidemiological analysis on myocarditis incidence in the era of SARS–CoV–2 and respective vaccination. Results We enrolled 48 patients, among which 37 were diagnosed during SARS–CoV–2 pandemic. 86% were male, and mean age at diagnosis was 31 years old; the vast majority did not show major modifiable CV risk factors (apart from cigarette smoking: 42%) or previous/comorbid CV conditions. Median LVEF (by CMR) at diagnosis was 56%, with 3 patients (6%) with LVEF &amp;lt; 47%. Median hsTnI and CRP peaks were respectively 7317 ng/L and 4,5 mg/dl. We reported 6 (12.5%) arrhythmic events during index hospitalization (1 patient had sustained VT and 5 had non–sustained VT). 8 out of 37 patients with myocarditis during SARS–CoV–2 outbreak reported previous COVID–19, with a median time of 130 days from infection, but only 1 had myocarditis as part of its clinical course. 16 patients had already received at least one SARS–CoV–2 vaccine dose (median: 2 doses) at diagnosis, with a median time of 117 days from dose administration (only two patients were diagnosed &amp;lt; 30 days from last administration). Conclusions Myocarditis epidemiology of our cohort seems to reflect available incidence data; furthermore, myocarditis as part of COVID–19 course or occurring shortly after vaccination appears to be an uncommon event. Our cohort consisted only of low or intermediate risk presentations. Data about diagnosis in the “COVID era” suggest a relative “underdiagnosis” in the previous period.

Soluble biomarkers for Neuromyelitis Optica Spectrum Disorders: a mini review

The Neuromyelitis Optica Spectrum Disorders (NMOSD) constitute a spectrum of rare autoimmune diseases of the central nervous system characterized by episodes of transverse myelitis, optic neuritis, and other demyelinating attacks. Previously thought to be a subtype of multiple sclerosis, NMOSD is now known to be a distinct disease with unique pathophysiology, clinical course, and treatment options. Although there have been significant recent advances in the diagnosis and treatment of NMOSD, the field still lacks clinically validated biomarkers that can be used to stratify disease severity, monitor disease activity, and inform treatment decisions. Here we review many emerging NMOSD biomarkers including markers of cellular damage, neutrophil-to-lymphocyte ratio, complement, and cytokines, with a focus on how each biomarker can potentially be used for initial diagnosis, relapse surveillance, disability prediction, and treatment monitoring.