Comparison of Relapsing Polychondritis Patients with and Without Respiratory Involvement Based on Chest Computed Tomography: A Retrospective Cohort Study

Background Relapsing polychondritis (RP) patients with tracheal cartilage involvement are different from other patients. The objectives of this study were to compare the clinical features and disease patterns between respiratory involvement subgroup and non-respiratory involvement subgroup according to chest computed tomography. Method We performed a retrospective cohort study collected RP patients hospitalized at the Beijing Chao-Yang Hospital between January 2012 - August 2021. Results The incident of costochondritis was more frequent in RP patients with respiratory involvement(p=0.03), the incidence of inflammatory eye disease(p=0.001) and auricular chondritis(p=0.001) was less frequent in RP respiratory involvement patients, compared with those of RP patients without respiratory involvement. Correlation analysis showed that a negative correlation between respiratory involvement and auricular chondritis (r=-0.58, p < 0.01), and between respiratory involvement and inflammatory eye disease (r=-0.45, P < 0.01). Auricular chondritis was positively correlated with inflammatory eye disease (r=0.49, P < 0.01). Compared with non-respiratory involvement subgroup, the incidence of pulmonary infection marginally increased in respiratory involvement subgroup(p=0.06). Inflammatory indexes except for CAR were significantly higher in respiratory involvement subgroup, subgroup analysis found that there was no significant relationship between inflammatory indexes and pulmonary infection. Conclusion RP patients with respiratory involvement was characterized by higher rate of costochondritis and pulmonary infection, fewer inflammatory eye disease and auricular chondritis compared to non-respiratory involvement. Increase inflammatory indexes may suggested that patients with respiratory involvement had a higher disease activity index of RP. The probability of survival was not significant between two subgroups.

Clinical characteristics and disease patterns of patients with relapsing polychondritis: a retrospective cohort

Background Relapsing polychondritis (RP) is a rare autoimmune disease affected various cartilage, Patients with tracheal cartilage involvement are different from other patients. The objectives of this study were to allocated RP patients into two subgroups by chest computed tomography (CT) and compare the clinical features and disease patterns of each group.Methods A retrospective cohort study collected RP patients hospitalized at the Beijing Chao-Yang Hospital between January 2012 - August 2021. Patients were divided into two groups: respiratory involvement group and non-respiratory involvement group according to chest CT.Results In our study, respiratory involvement found in 59.7% (n=43) patients, which had higher rate of costochondritis, fewer rate of Inflammatory eye disease and auricular chondritis than those in non-respiratory involvement. Compared with non-respiratory involvement subgroup, The incidence of pulmonary infection marginally increased and those inflammatory indexes except for CAR were significantly higher in respiratory involvement subgroup, further subgroup analysis found that there was no significant relationship between inflammatory indexes and pulmonary infection. Finally, 5 patients died during the follow-up in this cohort with a median follow-up time of 6 years (range 3-8 years).Conclusion 59.7% of patients had respiratory involvement according to chest CT findings in our cohort, which had a strong inverse relationship between respiratory and auricular, ocular involvement. Increase inflammatory indexes were not correlated with pulmonary infection, suggesting that patients with respiratory involvement had a higher disease activity index of RP. The probability of survival was not found significant in two subgroups.

Impact of SARS-CoV-2 Infection Among Non-Invasive Ventilated ALS Patients

Background: The impact of SARS-CoV-2 infection among neuromuscular diseases with respiratory involvement, including amyotrophic lateral sclerosis (ALS), is still to be elucidated. Objectives: We aim to characterize the clinical outcome of ALS patients non-invasive ventilated (NIV), following SARS-CoV-2 infection. Methods: We analyzed retrospectively our patients followed regularly at our ALS clinic, from the beginning of the COVID-19 pandemic (middle March 2020) to March 2021. We included patients on NIV with a documented SARS-CoV-2 infection. We recorded demographic and clinical data, including from the acute infectious illness. Results: Three men with spinal-onset ALS are described, mean age of onset was 55±9.1 years (45–61), and mean disease duration was 17.5±15.9 months (6.1–41). All of them were wheelchair-bounded, with a mean ALSFRS-R of 15.3±0.6 (15–16). One patient used NIV 15 hours/day, 2 between 4 to 7 hours/day, and all used assisted coughing twice daily. None had coexistent comorbidities. They were managed for SARS-CoV-2 infection as outpatients with fluticasone, bronchodilators, azithromycin and increasing frequency of assisted coughing. Supplemental oxygen (mean of 2 liters per minute) was needed in two patients, and one required NIV also during the daytime. Total recovery from SARS-CoV-2 infection was observed in all, despite being in an advanced stage of their disease, with severe respiratory involvement. Conclusions: Prompt medical treatment is recommended for ALS patients with severe disease infected by SARS-CoV-2.

Prominent Respiratory Involvement Featured in High-Risk Screening for Late-Onset Pompe Disease in China

Backgroud: Pompe disease is a rare metabolic disorder with available enzymatic replacement therapy. Contrasting with the classic infantile form, the others subtypes have a heterogeneous presentation that makes an early and accurate diagnosis difficulty. A multicenter observational study was aimed to assess the prevalence of late-onset Pompe disease (LOPD) in high-risk population, using dried blood spot (DBS) as a main screening tool.Methods: 20 Chinese neuromuscular centers were involved in the early LOPD screening study. Inclusion criteria were: (1) age ≥1 years, (2) either one of a) persistent hyperCKemia; or b) muscle weakness of axial and/or limb-girdle muscles; or c) unexplained restrictive respiratory insufficiency. Enzymatic activity of acid α-glucosidase (GAA) was measured on DBS by tandem mass spectrometry (MS/MS) assay. For the final diagnosis genotype was assessed by next-generation sequencing.Result: In a 9-month period, we studied 492 cases: 26 positive samples (5.3%) were detected by DBS screening. Molecular studies finally confirmed LOPD diagnosis in 8 cases (1.6%). The GAA activities in individuals bearing pseudodeficiency alleles were well separated from those in LOPD patients by MS/MS assay. The median interval from the onset of symptoms to diagnosis was 5 years. Besides axial/proximal muscle weakness, all patients showed respiratory insufficiency with a mean forced vital capacity of predicted of 48%. The level of creatine kinase ranged from normal to no more than 5-fold of upper normal limit. LOPD with isolated hyperCKemia was not identified.Conclusions: This study confirms that DBS test is a reliable method for screening for LOPD. Respiratory insufficiency is earlier and more severe among Chinese LOPD patients. LOPD presented with paucisymptomatic hyperCKemia. Therefore, a prompt diagnosis is critical to prognosis.

Bilateral basal ganglia ischemia associated with COVID-19: a case report and review of the literature

Background Coronavirus disease 2019, caused by the severe acute respiratory syndrome coronavirus 2, has a broad clinical spectrum, from asymptomatic to multi-organ dysfunction. Acute cerebrovascular events associated with coronavirus disease 2019 are mainly due to the severe acute respiratory syndrome coronavirus 2-induced prothrombotic state. Bilateral basal ganglia ischemia is rarely reported. Case presentation We report the case of a 64-year-old Asian (Pakistani) gentleman who presented initially with fever, cough, and shortness of breath, likely due to respiratory involvement by severe acute respiratory syndrome coronavirus 2. Later, he developed bilateral lower limb pain, followed by confusion and decreased level of consciousness. Accentuated large hypodense opacities were seen in the left and right basal ganglia, with mass effects on the left frontal horn. Conclusion This case demonstrates the importance of neuroimaging in the effective management of patients with neurological signs associated with coronavirus disease 2019.

Multisystem inflammatory syndrome in adults (MIS-A) associated with SARS-CoV-2 infection with delayed-onset myocarditis: case report

Background During the Coronavirus disease 2019 (COVID-19) pandemic, reports have emerged of a multisystem inflammatory syndrome in adults (MIS-A). Multisystem inflammatory syndrome in adults can affect various organ systems, including cardiovascular, gastrointestinal, and neurologic systems without significant respiratory involvement. Case summary A previously healthy 43-year-old man presented with fevers and abdominal pain then rapidly deteriorated into cardiogenic shock. His constellation of symptoms along with elevated inflammatory markers in the setting of a recent SARS-CoV-2 infection was consistent with the diagnosis of MIS-A. He also had a comprehensive infectious workup that was unremarkable, ruling out other potential infectious aetiologies for his presentation. He subsequently improved through supportive measures and after administration of intravenous immunoglobulin (IVIG). He later demonstrated recovery of cardiac function and cardiac magnetic resonance imaging (MRI) showed signs consistent with myocarditis. Discussion As the COVID-19 pandemic continues to be an ongoing issue, it is important to recognize MIS-A, a rare and potentially deadly clinical syndrome that can lead to profound cardiovascular complications. Non-invasive imaging modalities such as cardiac MRI can play a role in the identification of myocarditis. In addition to supportive management, adjunctive therapies such as IVIG may be efficacious in MIS-A and should be further investigated.

Delayed Respiratory Insufficiency and Extramuscular Abnormalities in Selenoprotein N-Related Myopathies

Background: Selenoprotein N-related myopathies (SEPN1-RMs) are a subset of congenital myopathies caused by mutations of Selenoprotein N gene (SELENON or SEPN1). Clinical phenotype is considered as highly consistent and little attention has been given to the extramuscular abnormalities.Methods: We reported clinical, histopathological, and genetic features of four Chinese patients with SEPN1-RM and performed literature review on delayed respiratory insufficiency and extramuscular involvement.Results: A total of four patients exhibited both the typical and atypical clinical features of SEPN1-RM. The classical manifestations included axial and limb girdle weakness, spinal rigidity, scoliosis, respiratory insufficiency, and multiminicore morphological lesions. However, high interindividual variability was noticed on disease severity, especially the onset of respiratory involvement. Two adult patients postponed respiratory insufficiency to the third decade of life, while two juvenile patients manifested early hypoventilation with puberty exacerbation. As atypical features, extramuscular involvement of weight gain, subcutaneous adipose tissue accumulation, intellectual disability, and mild cardiac changes were observed. Molecular findings revealed three novel mutations of SELENON such as c.1286_1288 del CCT, c.1078_1086dupGGCTACATA, and c.785 G&gt;C. Ten cases with delayed respiratory insufficiency were identified from previous publications. A total of 18 studies described extramuscular abnormalities including joint contractures, alterations of body mass index (BMI), mild cardiac changes, and insulin resistance. Intellectual impairment was extremely rare.Conclusion: SEPN1-RM should be considered as a differential diagnosis in adult patients with delayed respiratory involvement. Extramuscular involvement such as body composition alterations deserves more clinical attention. The novel mutations of SELENON widened the genetic spectrum of patients with SEPN1-RM.

Positive aspects, negative aspects and challenges associated with stem cell therapy for COVID - 19: A Mini-Review

: Like any other pandemic, the Covid-19 scenario has also demanded effective treatment options. The circumstances demand to utilize all the possible weapons in the armamentarium. There have been many issues regarding the short-term and long-term safety and efficacy of these options. Some options are like uncharted seas and these need a detailed and critical review with respect to safety, efficacy, feasibility and financial constraints. Mesenchymal stem cells (MSCs) therapy has been studied for many years for its potential role in diseases with complex pathogenesis. Its efficacy in controlling cytokine imbalance and immuno-modulatory properties is well proven. These effects are being extensively studied for potential extension of the benefits for an effective option for management of COVID-19 patients with severe respiratory involvement. In this mini-review, an attempt has been made to review positive aspects, negative aspects, and challenges influencing MSCs therapy in the management of COVID-19 disease. The results of various studies and literature reviews show that MSCs therapy can be considered as one of the potential options.

Elevated cytokines and chemokines in peripheral blood of patients with SARS-CoV-2 pneumonia treated with high-titer convalescent plasma

The global SARS-CoV-2 coronavirus pandemic continues to be devastating in many areas. Treatment options have been limited and convalescent donor plasma has been used by many centers to transfer passive neutralizing antibodies to patients with respiratory involvement. The results often vary by institution and are complicated by the nature and quality of the donor plasma itself, the timing of administration and the clinical aspects of the recipients. SARS-CoV-2 infection is known to be associated with an increase in the blood concentrations of several inflammatory cytokines/chemokines, as part of the overall immune response to the virus and consequential to mediated lung pathology. Some of these correlates contribute to the cytokine storm syndrome and acute respiratory distress syndrome, often resulting in fatality. A Phase IIa clinical trial at our institution using high neutralizing titer convalescent plasma transfer gave us the unique opportunity to study the elevations of correlates in the first 10 days after infusion. Plasma recipients were divided into hospitalized COVID-19 pneumonia patients who did not (Track 2) or did (Track 3) require mechanical ventilation. Several cytokines were elevated in the patients of each Track and some continued to rise through Day 10, while others initially increased and then subsided. Furthermore, elevations in MIP-1α, MIP-1β and CRP correlated with disease progression of Track 2 recipients. Overall, our observations serve as a foundation for further study of these correlates and the identification of potential biomarkers to improve upon convalescent plasma therapy and to drive more successful patient outcomes.