Catastrophic antiphospholipid syndrome presented with coronary thrombosis, renal impairment, and suspected diffuse alveolar hemorrhage treated with rituximab biosimilar (CT-P10)

Catastrophic antiphospholipid syndrome (CAPS) is a lethal disease that occurs suddenly and progresses to multi-organ failure. We present a case of CAPS successfully treated with the rituximab biosimilar CT-P10. A 38-year-old man was referred with a sustained fever and unexplained elevated creatinine levels. Cardiac arrest by ventricular fibrillation occurred upon arrival at the hospital. We diagnosed probable CAPS because of coronary thrombus, renal impairment, suspected diffuse alveolar hemorrhage, and positive anticardiolipin antibody immunoglobulin G. We performed percutaneous coronary intervention for the cardiac arrest, and treated him with extracorporeal membrane oxygenation, mechanical ventilation, and continuous renal replacement therapy. When CAPS was diagnosed, we administered CT-P10 after administering high-dose glucocorticoid. Our case suggests that the use of a rituximab biosimilar is economically efficient in the treatment of CAPS, as in other rheumatic diseases. The patient was cured without recurrence at the 2-year follow-up.

Nitric oxide synthase-2 (CCTTT)n polymorphism is associated with local gene expression and clinical manifestations in patients with chronic rhinosinusitis

Introduction Nitric oxide (NO) is synthesized through NO synthase (NOS). The proximal NOS2 gene promoter contains the pentanucleotide CCTTT repeat polymorphism. We examined whether CCTTT repeats are associated with NOS2 expression in the sinonasal tissues and clinical manifestations in patients with chronic rhinosinusitis. Methods Mucosal specimens were obtained from the ethmoid sinus and inferior turbinate of 30 eosinophilic chronic rhinosinusitis (ECRS) and 28 non-ECRS patients. CCTTT repeats were classified into short alleles (S), with less than or equal to 14, and long alleles (L), with more than 14. The subjects were classified into the L/S + L/L and S/S groups. Results In ECRS, the NOS2 mRNA levels of the ethmoid sinus mucosa were significantly higher in the L/S + L/L group than in the S/S group (median, 1.66 and 0.77, respectively). On the ther hand, ECRS patients showed no significant difference in the NOS2 mRNA level of the inferior turbinate between the L/S + L/L group and the S/S group (median, 0.63 and 0.88, respectively). In ECRS, preoperative SNOT-22 were significantly higher in the L/S + L/L group than in the S/S group, whereas the former group showed a lower postoperative recurrence risk. Conclusion CCTTT repeat polymorphism in the NOS2 promotor gene may be a useful indicator to evaluate ECRS severity and prognosis.

Systemic lupus erythematosus after delivery and myasthenia gravis with COL6A1 gene mutation: A case report

The coexistence of systemic lupus erythematosus (SLE) and myasthenia gravis (MG) is rarely reported, especially the appearance of SLE before MG. In addition to the production of autoantibodies after thymectomy, gene mutation may be an important contributing factor to the overlap of SLE and MG. Here, we report a case of a female patient diagnosed with SLE before MG and found to carry the heterozygous variation COL6A1 c. 2608G>A. We propose that this gene variation weakens the function of COL6A1 and indirectly activates STAT1, resulting in the phenotype of these two autoimmune diseases. This report suggests that it is feasible to explore common pathogenic genes in SLE and MG through future large-scale research.

The impacts of oxygen and pentoxifylline in hypoxic condition

Introduction:Among major trauma patients in the emergency department, the leading cause of morbidity and mortality is a hemorrhagic shock. The low oxygen flow with hypovolemia in trauma patients is believed to play a significant role. Hence, oxygen supply is essential in severe trauma patients with massive hemorrhage. This study aimed to investigate the effect of oxygen supply in hypoxic condition and variable treatments such as pentoxifylline (PTX), glycerol, hypertonic saline (HTS), protease inhibitor, and dexamethasone (DEXA) in macrophage and T cells. Method:Nitric oxide synthase (iNOS) and macrophage migration inhibitory factor (MIF) were measured for macrophage. MIF, interleukin (IL)-2, and IL-8 were measured for T cells. T cell viability was measued by MTT assay. Results: Pentoxifylline decreased iNOS expression mostly followed by glycerol under hypoxia. Under the hyperoxia, PTX and other treatments decreased iNOS expressions in macrophage. MIF expression was lowered with PTX under hypoxia. PTX, glycerol, HTS, and protease inhibitor were effective under hyperoxia in macrophage. PTX increased T cell survival under hypoxia. Under the hyperoxia, IL-2 expressions were upregulated with PTX, glycerol, and HTS. PTX and other treatments were effective for IL-8. Our results indicate that the PTX and the other agents tested reversed the effects of stimulation of lipopolysaccharide, PGE2 in hypoxia or hypoxia. Conclusion:Our study demonstrated potential usefulness in improving immune systems during severe inflammatory conditions similar to septic shock possibly caused by massive hemorrhage.

Clinical characteristics of patients with acquired immunodeficiency syndrome having respiratory symptoms as the initial manifestations: A retrospective study

The aim of the study was to investigate clinical features of patients with AIDS having respiratory symptoms as initial manifestations and help in the early diagnosis. Eighty-eight patients admitted to the Shanghai Pulmonary Hospital were included in the study. General data, clinical manifestations, laboratory tests, chest computed tomography (CT) imaging features, treatments, and prognosis were analyzed. Peripheral leukopenia, lymphopenia, hypoxemia, and reduced percentage of CD4+ T lymphocytes were found in 25.6%, 43.6%, 27.5%, and 94.9% of the patients, respectively. Pneumocystis jirovecii pneumonia (PCP) was the most frequent cause of opportunistic pulmonary infection. Patients with PCP had more bilateral lung involvement and ground-glass shadow in CT manifestations. A follow-up of the 43 patients transferred to the Public Health Center showed improvement in 27 (62.8%), stabilization in 4 (9.3%), worsening in 1 (2.3%), and death in 11 (25.6%) patients. Detailed medical history recording, screening of human immunodeficiency virus antibody, and flow cytometry would improve the diagnostic efficiency of AIDS in patients with diffuse ground-glass shadow in chest CT. Early and empirical treatment could improve the prognosis.

Oxidative stress in common variable immunodeficiency

Common variable immunodeficiency (CVID) is a heterogenous group of immunologic disorders of unknown etiology. Alterations of the normal cellular balance due to an increase in reactive oxygen species and/or decrease in antioxidant defense may lead to increased oxidative stress. We aimed to evaluate the levels of oxidative stress biomarkers in patients with CVID who had different presentations. We investigated the serum catalase (CAT), erythrocyte superoxide dismutase (SOD), erythrocyte reduced glutathione as antioxidants and serum malondialdehyde levels as lipid peroxidation marker in patients with CVID in Uludag University Hospital Department of Pediatric Allergy and Immunology’s outpatient clinics. In the analysis, there were 21 patients and 27 matched healthy controls. The median levels of CAT in patients with CVID was significantly lower than in healthy controls ( p = 0.04). Among the patients with CVID, 19% had autoimmune disease, one had Sjögren’s syndrome, one had autoimmune alopecia, one had juvenile rheumatoid arthritis, and one had chronic inflammatory demyelinating polyneuropathy. Patients with autoimmune complications had significantly lower CAT levels compared to the ones without autoimmune diseases ( p = 0.03). The patients without non-infectious complications (NICs) had lower SOD levels than the patients with NICs ( p = 0.05). The analysis of oxidative stress markers in the patients with CVID suggested a series of abnormalities in the anti-oxidant system. The clinical syndrome associations may be a useful tool for future studies to set prediction markers for the prognosis of patients with CVID.

Creation of a specific and separated pediatric intra-hospital pathway in primary level hospitals during the era of COVID-19

Every new pandemic forces us to start new specific behaviors both in the civil life and within the hospitals trying to contain the spreading of the infection and preserve the more fragile people. In this regard, at the debut of Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-CoV-2) pandemic, our Local Health Agency had drastically modified every clinical and organizational pathways in order to limit the diffusion of the infection as well as to maintain a good quality of care and preserve healthcare workers. We report how we have modified the usual pediatric intra-hospital pathways in our primary level hospital to avoid mixing children with suspected and non-suspected symptoms of SARS-CoV-2 infection. Before every hospitalization, regardless of symptoms, each child and him/her parent/caregiver are undergone to rapid antigenic and molecular swab to rule out a SARS-CoV-2 infection; hence, positive patients are transferred to Pediatric Unit of third level hospital equipped by a Pediatric COVID Intensive Unit. We think the healthcare behaviors described in this manuscript can help to reduce the intra-hospital spreading of SARS-CoV-2, although children seem to have a minimal role in the dissemination, but we cannot let down your guard. Simultaneously we observed that the overall children requiring inpatient pediatric evaluation and hospitalization have dramatically decreased from the beginning of pandemic.

Cardioprotective effects of Ginsenoside compound-Mc1 and Dendrobium Nobile Lindl against myocardial infarction in an aged rat model: Involvement of TLR4/NF-κB signaling pathway

Aging is the crucial co-morbidity that prevents the full cardioprotection against myocardial ischemia/reperfusion (I/R) injury. Combination therapy as a promising strategy may overcome this clinical problem. This study aimed to investigate the cardioprotective effects of Ginsenoside compound-Mc1 (GMc1) and Dendrobium Nobile Lindl (DNL) in myocardial I/R injury and explore the involvement of the TLR4/NF-κB signaling pathway in aged rats. In vivo I/R injury and myocardial infarction was established by temporary coronary ligation in 22–24 months’ old Sprague Dawley male rats. GMc1 (10 mg/kg) and DNL (80 mg/kg) were administered intraperitoneally for 4 weeks and orally for 14 days, respectively, before I/R injury. Infarct size was measured through triphenyl-tetrazolium-chloride staining. ELISA assay was conducted to quantify the levels of cardiotroponin, and myocardial content of TNF-α and glutathione. Western blotting was employed to detect the expression of TLR4/MyD88/NF-κB proteins. GMc1 and DNL significantly reduced the infarct size to a similar extent ( p < 0.05) but their combined effect was greater than individual ones ( p < 0.01). Combination therapy significantly restored the left ventricular end-diastolic and developed pressures at the end of reperfusion as compared with the untreated group ( p < 0.01). Although the GMc1 and DNL reduced the levels of inflammatory cytokine TNF-α and increased the contents of antioxidant glutathione significantly, their individual effects on the reduction of protein expression of TLR4/MyD88/NF-κB pathway were not consistent. However, their combination could significantly reduce all parameters of this inflammatory pathway as compared to untreated I/R rats ( p < 0.001). Therefore, the combined treatment with GMc1 and DNL increased the potency of each intervention in protecting the aged hearts against I/R injury. Reduction in the activity of the TLR4/MyD88/NF-κB signaling pathway and subsequent modulation of the activity of inflammatory cytokines and endogenous antioxidants play an important role in this cardioprotection.

Hepatoprotective effect of galangin on carbon tetrachloride-induced hepatotoxicity via the LKB1/AMPK pathway

To investigate the protective effects of galangin on liver toxicity induced by carbon tetrachloride (CCl4) in mice. Mouse hepatotoxicity model was established by intraperitoneal injection (i.p.) of 10 ml/kg body weight CCl4 that diluted with corn oil to a proportion of 1:500 on Kunming mice. The mice were randomly divided into five groups named control group, model group, and 1, 5, and 10 mg/kg galangin group. The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed by ELISA. Liver histopathological examination was observed via optical microscopy. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), and glutathion (GSSG) were analyzed to assess oxidative stress. Finally, western blot assay was carried out to analyse the expression levels of total AMP-activated protein kinase (AMPK), phospho-AMPK (p-AMPK), total liver kinase B1 (LKB1), and phospho-LKB1 (p-LKB1). Compared with the control group, in the model group, the levels of AST, ALT, MDA, and GSSG increased significantly ( p < 0.01); the activity of SOD and GSH decreased significantly ( p < 0.01); and the histopathological examination revealed liver necrosis. However, treatment with galangin (5 and 10 mg/kg) significantly reversed these CCl4-induced liver damage indicators. Furthermore, treatment with galangin (10 mg/kg) significantly increased the p-AMPK and p-LKB1 expression levels ( p < 0.01). This study supports the hepatoprotective effect of galangin against hepatotoxicity, perhaps occurring mainly through the LKB1/AMPK-mediated pathway.

Tim-3 associated with apoptotic NK cells and disease activity in SLE

T cell immunoglobulin and mucin domain-containing molecule-3 (Tim-3) has been found to play important roles in systemic lupus erythematosus (SLE), however, whether Tim-3 is involved in apoptosis of NK cells in SLE remains unknown. The proportion of CD3−CD56+ NK cells and the percentage of AnnexinV+ NK cells were analyzed by flow cytometry in SLE patients and healthy controls. Tim-3 expression on NK cells was also evaluated by flow cytometry. We firstly observed a decreased proportion of NK cells and an increased proportion of apoptotic NK cells in SLE patients. The proportion of apoptotic NK cells was positively correlated with anti-dsDNA and SLEDAI. Tim-3 expression on NK cells was up-regulated in SLE patients. Further analysis showed that Tim-3 expression on NK cells was negatively correlated with the proportion of apoptotic NK cells, anti-dsDNA and SLEDAI, while positively correlated with the proportion of NK cells. The present results suggest that Tim-3 might play roles in SLE by regulating the apoptosis of NK cells and Tim-3 might serve as a potential target for the treatment of SLE.