Disseminated Tuberculosis Associated Hemophagocytic Lymphohistiocytosis in a Pregnant Woman With Evans syndrome: A Case Report and Literature Review.

Background: Tuberculosis (TB) is a leading cause of morbidity and mortality in underdeveloped and developing countries. Disseminated TB may induce uncommon and potentially fatal secondary hemophagocytic lymphohistiocytosis (HLH). Timely treatment with anti-tuberculosis therapy (ATT) and downmodulation of the immune response is critical. However, corticosteroid treatment for TB-associated HLH remains controversial. Herein, we report a successful case of disseminated TB-associated HLH in a pregnant woman with Evans syndrome accompanied by a literature review. Case Presentation: A 26-year-old pregnant woman with Evans syndrome was transferred to the Third Affiliated Hospital of Sun Yat-Sen University because of severe pneumonia. She presented with cough, fever, and aggravated dyspnea. Nested polymerase chain reaction for Mycobacterium tuberculosis (M. tuberculosis) complex in sputum was positive. Sputum smear sample for acid-fast bacilli was also positive. Metagenome next-generation sequencing (mNGS) of the bronchoalveolar lavage fluid identified 926 DNA sequence reads and 195 RNA sequence reads corresponding to M. tuberculosis complex, respectively. mNGS of blood identified 48 DNA sequence reads corresponding to M. tuberculosis. There was no sequence read corresponding to other potential pathogens. She was initially administered standard ATT together with a low dose of methylprednisolone (40 mg/day). However, her condition deteriorated rapidly with high fever, acute respiratory distress syndrome, pancytopenia, and hyperferritinemia. Bone marrow smears showed hemophagocytosis. And caseating tuberculous granulomas were found in the placenta. A diagnosis of disseminated TB-associated HLH was made. Along with the continuation of four drug ATT regimen, therapy with a higher dose of methylprednisolone (160 mg/day) combined with immunoglobulin and plasma exchange was managed. The patient's condition improved, and she was discharged on day 19. Her condition was good at follow-up with the continuation of the ATT. Conclusions: Clinicians encountering patients with suspected TB accompanied by unexplainable inflammation not responding to ATT should consider complications with HLH. Timely administration of ATT combined with corticosteroids may result in a favorable outcome.

Successful treatment of mycobacterial infection associated hemophagocytic lymphohistiocytosis with etoposide and anti-tuberculous therapy: a case report.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially life-threatening disorder characterized by an exacerbated but ineffective inflammatory response, which can be classified as primary and secondary HLH. HLH associated with Mycobacterium tuberculosis is uncommon. This case report accounted an immunocompetent patient who was confirmed to be Mycobacterium infection, or rather, highly suspected tuberculosis (TB) associated HLH, with a favorable outcome. CASE PRESENTATION: A 36-year-old man presented with persistent fever, pancytopenia, and hyperferritinemia. A bone marrow smear demonstrated hemophagocytosis, and pathological examination of lung biopsy was positive for acid-fast bacilli, which established the diagnosis of Mycobacterium infection and HLH. Then the patient treated successfully with anti-TB therapy, along with 8 weeks of etoposide. CONCLUSION: This case emphasizes that HLH should be kept in mind when clinicians encounter a patient with severe infection presenting with pancytopenia and hyperferritinemia. Given the high mortality, early diagnosis and appropriate therapy can provide patients with a favorable prognosis.

Therapeutic plasma exchange and continuous renal replacement therapy for severe hyperthyroidism and multi-organ failure: A case report.

BACKGROUND: Severe hyperthyroidism is a life-threatening exacerbation of thyrotoxicosis, characterized by high fever and multiorgan failure. The most common medical treatments are administration of antithyroid drugs and radioactive iodine, and thyroidectomy. In some patients, antithyroid therapy is limited due to serious adverse effects or failure to control disease progression. In some extreme cases, such as thyroid storm, conventional therapy alone does not yield effective and rapid improvement before the development of multiorgan failure. CASE SUMMARY: This report describes a Chinese patient with severe hyperthyroidism accompanied by multiorgan failure, who was transferred to the medical intensive care unit of our hospital. The patient presented with palpitations, vomiting, diarrhea, and shortness of breath for a week. Laboratory tests showed elevation of thyroid hormones. Hepatic failure occurred with high aminotransferase levels and jaundice. Given her abnormal liver function and medication history, we could not exclude diagnosis of propylthiouracil-induced hepatic failure. Moreover, she also suffered from heart failure. Therapeutic plasma exchange (commonly known as TPE) and continuous renal replacement therapy (commonly known as CRRT) were used as life-saving therapy, which resulted in notable improvement of clinical symptoms and laboratory tests. CONCLUSION: Combined TPE and CRRT are safe and effective for patients with hyperthyroidism and multiorgan failure.

Single Femoral Venous Drainage Versus Both Vena Cava Drainage in Isolated Repeat Tricuspid Valve Surgery.

To assess the potential advantages of minimally invasive surgery using a single femoral venous drainage method versus femoral venous and superior vena cava or jugular venous drainage method during repeat tricuspid valve surgery.From January 2010 to December 2016, 50 repeat tricuspid valve procedures were performed using a minimally invasive approach without aortic cross-clamping at our institution. The arterial cannula was inserted into the femoral artery, and at the same time, the venous cannula was placed in the femoral vein in 28 patients (FV group) during cardiopulmonary bypass (CPB). The venous cannula was inserted into the femoral vein and the superior vena cava or jugular vein in 22 patients (FSV group).Overall, 36 patients underwent tricuspid valve replacement (TVR) and 14 patients underwent tricuspid valvuloplasty (TVP). The CPB time and operation time, respectively, were 72.96 ± 25.90 minutes versus 78.59 ± 31.95 minutes (P = 0.495) and 170.75 ± 73.31 minutes versus 228.87 ± 61.45 minutes (P = 0.004) in the FV group versus the FVS group. There were no significant differences in the ventilator-assisted time, the first-day LVEF, and the intensive care unit (ICU) stay between the FV group and the FSV group.Both types of drainage were effective and could ensure safety during the operative procedure. The vacuum-assisted single femoral venous drainage method simplified the minimally invasive isolated repeat tricuspid valve surgical process more significantly and is the more appropriate choice.

Superior vena cava reconstruction under the left internal jugular vein to left femoral vein bypass support.

The complete surgical resection of malignant thymoma is recommended. We present a rare case of tumor resection and superior vena cava (SVC) reconstruction under veno-venous bypass support from the left internal jugular vein to the left femoral vein. The full amount of systemic heparinization (3 mg/kg) was avoided. The surgical pathology revealed thymic squamous cell carcinoma. No complications such as fatal extensive bleeding, coagulopathy, thromboembolism or transfusion reaction were found postoperatively. The patient was discharged home uneventfully. The support of this veno-venous bypass allows a safe and feasible thymic tumor resection and SVC reconstruction.

A New Venous Drainage Technique in Minimally Invasive Redo Tricuspid Surgery: Vacuum-Assist Venous Drainage via a Single Femoral Venous Cannula.

OBJECTIVE: To summarise the experiences of applying vacuum-assist with a single femoral venous cannula drainage technique in minimally invasive isolated redo tricuspid surgery. METHODS: Eight consecutive patients underwent minimally invasive redo tricuspid surgery through a right thoracotomy at our institute. All of the patients had isolated significant tricuspid regurgitation after previous cardiac surgeries, and received minimally invasive redo tricuspid surgery. The arterial cannula was inserted into the femoral artery, and at the same time, the venous cannula was placed into the femoral vein. The venous cannula was guided by transoesophageal echocardiography and reached the superior vena cava (SVC). The caval veins did not need to be snared with the heart beating during the operation, but applying the vacuum-assisted venous drainage (VAVD) controller was necessary. RESULTS: This cannulation makes it possible to achieve adequate drainage (3.48±0.44L/min) and accomplishes complete arterial perfusion. Most importantly, it guarantees a good visual field without blood and allows safe surgery. The average time of cardiopulmonary bypass (CPB) was 68.25±13.84min. The length of ICU and hospital stays were 4.13 ±3.52 days and 8.14±4.98 days, respectively. In eight patients, there was no early death in the hospital. One patient experienced acute renal dysfunction. CONCLUSION: Vacuum-assist venous drainage via a single femoral venous cannula in isolated redo tricuspid surgery is safe, effective, reliable, and significantly simplifies the procedure.

Regulatory effects of miR-155 and miR-146a on repolarization and inflammatory cytokine secretion in human alveolar macrophages in vitro.

Macrophages play an important role in inflammatory responses; however, miRNA-mediated repolarization of macrophages is essential for fulfilling this function. To clarify a series of changes at the RNA level in alveolar macrophages under normal and inflammatory conditions, bronchial alveolar lavage liquid (BALF) was collected from healthy volunteers or patients with pneumonia. This approach, which differs from that used in previously, provides more accurate information about the states of macrophages in different lung microenvironments. In this study, the density plots of macrophage subtypes (M1 and M2) in the BALF of healthy volunteers differed from that of the patients with pneumonia. The M2 subtype dominated in healthy volunteers and was rapidly repolarized to M1 in response to miRNA-mediated gene regulation. Differential miRNA expression in the two macrophage subtypes revealed lower expression of miR-155 and MIR-146a in patients with pneumonia compared with healthy volunteers; this may be related to inflammation and the use of anti-inflammatory drugs. We also found increased TNF-α and IL-6 expression at the RNA level, while macrophage galactose-type C-type lectin 1 (MGL-1) expression decreased with downregulation of miR-155 and miR-146a expression. These results indicate that the gene regulation mediated by miR-155 and miR-146a contributes to human alveolar macrophage phenotype repolarization, thus leading to an early switch from pro-inflammatory to anti-inflammatory cytokine production.

Intravitreal anti-VEGF injections for treating wet age-related macular degeneration: a systematic review and meta-analysis.

AIMS: Age-related macular degeneration (AMD) is the main cause of blindness. Anti-vascular endothelial growth factor is used to prevent further neovascularization due to wet AMD. The purpose of this systematic review was to investigate the effect and protocol of anti-vascular endothelial growth factor treatment on wet AMD. METHODS: A comprehensive literature search was performed in PubMed, Embase, the Cochrane Library, CNKI, and reference lists. Meta-analysis was performed using Stata12.0 software, best corrected visual acuity (BCVA), retinal thickness, and lesion size were evaluated. RESULTS: Twelve randomized controlled trials spanning from 2010 to 2014 and involving 5,225 patients were included. A significant difference was observed between the intravitreal ranibizumab (IVR) group and the intravitreal bevacizumab group (standard mean difference = -0.14, 95% confidence interval [CI] = -0.23 to -0.05). No significant differences were observed in best corrected VA, retinal thickness, or lesion size between IVR and the intravitreal aflibercept group. Compared to monthly injection, IVR as-needed injections (PRN) can raise VA by 1.97 letters (weighted mean difference = 1.97, 95% CI = 0.14-3.794). Combination therapy of IVR and photodynamic therapy can significantly raise VA by 2.74 letters when combined with IVR monotherapy (weighted mean difference = 2.74, 95% CI = 0.26-5.21). CONCLUSION: The superiority remains unclear between IVR and intravitreal bevacizumab in the treatment of neovascular AMD. Intravitreal aflibercept dosed every 2 months required fewer injection times, but produced similar efficacy as monthly IVR. IVR PRN could significantly increase VA. Combined with photodynamic therapy, IVR therapy could also increase VA effectively.

Vitreous proteomic analysis of idiopathic epiretinal membranes.

To understand the molecular mechanisms of idiopathic epiretinal membranes (iERMs), the vitreous proteomes of patients with iERMs were investigated. The vitreous proteome in patients with iERMs (n = 8) and donor samples (n = 8) was analysed using reversed phase high-performance liquid chromatography (RP-HPLC) coupled with electrospray ionization tandem mass spectrometry (ESI-MS/MS) and GeneGo Metacore™. This research followed the tenets of the Declaration of Helsinki for the use of human subjects. In this current study, 226 significant changes in protein abundance (abundance ratio >2, p < 0.01) were identified in the vitreous proteome of iERM patients compared to normal control vitreous, including 122 proteins that were present at lower levels and 104 proteins that were present at higher levels. In the iERM vitreous samples, complement components, inflammation-related proteins and matrix metalloproteinase were present at higher levels, while normal cytoskeleton proteins were present at lower levels. The top GeneGo pathway was "immune response", the top process network was "inflammation", and the top KEGG pathway was "coagulation cascades". The essential 2-node proteins of the network were estrogen receptor 1 (ESR1) and p300. Among those found at higher levels, ubiquitin-conjugating enzyme E2O (UBE2O) and complement C4A (C4A) were the most abundant proteins, and could be detected in each of the iERM vitreous samples. It can be concluded that iERMs are a complicated pathological process involving inflammation, immune response, and cytoskeleton remolding. UBE2O and C4A may be candidate biomarkers for iERMs.

Expression of IGFBP­6 in proliferative vitreoretinopathy rat models and its effects on retinal pigment epithelial­J cells.

Proliferative vitreoretinopathy (PVR) is one of the most common causes for failed retinal detachment surgeries. The aim of the present study was to investigate the role of insulin­like growth factor­binding protein­6 (IGFBP­6) in PVR using rat models and its effects on retinal pigment epithelial­J (RPE­J) cells. PVR Wistar rat models were administered intravitreal injection of RPE­J cells (1x106/5 µl) combined with platelet­rich plasma (1x107/5 µl). The concentration of IGFBP­6 in the vitreous and serum of rats was tested by an enzyme­linked immunosorbent assay and the expression of IGFBP­6 mRNA in the liver and retina of rats was determined by quantitative polymerase chain reaction (qPCR). The expression of IGFBP­6 mRNA in the RPE­J cells stimulated by vitreous or serum from PVR patients or normal volunteers was also determined by qPCR. The proliferation of RPE­J cells was evaluated by the 3­(4,5­dimethylthiazol­2­yl)­5­(3­carboxymethoxyphenyl)­2­(4­sulfophenyl)­2H­tetrazolium, inner salt (MTS) method. The success rate of PVR rat model induction at the 8th week was 89.5% (34/38). The concentration of IGFBP­6 in the vitreous and serum of PVR rats was significantly higher than that of the control group (P<0.05). The expression of IGFBP­6 mRNA in the retina of PVR rats was also significantly higher compared with the control group (P<0.05). The vitreous from PVR patients and donors significantly stimulated the expression of IGFBP­6 mRNA in the RPE­J cells (P<0.05). IGFBP­6 only inhibited IGF­II­stimulated proliferation but not the basal level of proliferation or the PDGF/VEGF­stimulated RPE­J cell proliferation. Thus, the trends and effects of IGFBP­6 provide the possibility of PVR therapeutic targets, with the vitreous representing a significant environmental factor in the progression of PVR.

Kininogen 1 and insulin-like growth factor binding protein 6: candidate serum biomarkers of proliferative vitreoretinopathy.

BACKGROUND: The aim was to validate whether kininogen 1 (KNG1) or insulin-like growth factor binding protein 6 (IGFBP-6) are serum biomarkers of proliferative vitreoretinopathy (PVR). METHODS: Samples from vitreous and corresponding serum samples were collected from patients with PVR. The donor vitreous samples and serum samples from healthy volunteers and volunteers who had undergone vitrectomies for other conditions were used as controls. The samples were subsequently analysed using Western blotting (WB) and enzyme-linked immunosorbent assay. RESULTS: The Western blotting outcomes indicated both IGFBP-6 and KNG1 could be specifically detected in the vitreous and serum samples of patients with PVR. The concentrations of KNG1 and IGFBP-6 were significantly higher in both vitreous and serum samples from patients with severe PVR than in the samples from patients with moderate PVR. The serum concentrations of KNG1 or IGFBP-6 had decreased by the post-vitrectomy examinations. The receiver operating characteristic (ROC) analyses when the concentrations of IGFBP-6 or KNG1 were greater than 181.4 pg/ml or 441.75 ng/ml, respectively, predicted severe PVR with both a sensitivity and specificity of over 70 per cent. When the concentrations of IGFBP-6 or KNG1 were greater than 98.5 pg/ml or 88.5 ng/ml, respectively, they predicted the PVR prognosis with both a sensitivity and specificity of 80 per cent. CONCLUSIONS: KNG1 and IGFBP-6 may be candidate serum biomarkers of PVR.

Inhibitory effects of simvastatin on staphylococcus aureus lipoteichoic acid-induced inflammation in human alveolar macrophages.

Staphylococcus aureus (S. aureus) is the most common bacterium in sepsis and pneumonia involving gram-positive bacteria. Lipoteichoic acid (LTA) is a cell wall component of gram-positive bacteria. It is a potent inducer of inflammatory mediators in human dendritic cells, human pulmonary epithelial cells, and murine macrophages. However, the effect of LTA on human alveolar macrophages (AMs) which are the major effector cells in host defense against respiratory tract infections has hardly been studied. Statins have anti-inflammatory, immunomodulatory, antioxidative, anticoagulant, and antibacterial activities. These effects may be contributed to reduce the markers of systemic inflammation. Emerging retrospective studies have demonstrated that statin use decreased the mortality of pneumonia. However, the precise mechanisms responsible for these effects are unclear. The purpose of this study is to define the role of S. aureus LTA in human AMs and the effects of simvastatin (SV) on LTA-stimulated human AMs. The results showed that LTA induced tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1ß), IL-8 mRNA expression, and suppressed IL-10 mRNA expression in human AMs. Simultaneously, LTA induced human AMs apoptosis. These effects were parallel with the up-regulation of the expression of NF-κB-P65 protein in the LTA-stimulated human AMs. The above effects of LTA on human AMs were inhibited significantly by SV. These data indicate that S. aureus LTA induces potent pro-inflammatory and pro-apoptotic effects on human AMs and statins exert anti-inflammatory effects by mediating inhibition of NF-κB activation and cytokine mRNA expression in human AMs. These results may explain, in part, the mechanisms responsible for favorable effects of statins on pneumonia.

Elucidation of the pathogenic mechanism of rhegmatogenous retinal detachment with proliferative vitreoretinopathy by proteomic analysis.

PURPOSE: To understand the molecular mechanisms of rhegmatogenous retinal detachment (RRD) with proliferative vitreoretinopathy (PVR), the vitreous proteome in RRD patients with severe PVR (grade C or D) was investigated. METHODS: The analysis of the vitreous proteome in RRD patients with PVR (n = 24) and donor samples (n = 8) was analyzed by one-dimensional (1D) SDS-PAGE and reverse-phase liquid chromatography tandem mass spectrometry (RP-LC-MS/MS). The data were analyzed using GeneGO MetaCore software. The research followed the tenets of the Declaration of Helsinki for the use of human subjects. RESULTS: In total, 516 and 364 proteins were identified in the vitreous of RRD patients with PVR and donor samples, including 48 overlapping proteins. In the PVR vitreous samples, the levels of extracellular (EC) proteins were increased and the levels of cytoskeleton proteins were decreased. In the pathologic process of PVR, inflammation was identified as an important GeneGo network. Furthermore, the complement and coagulation cascade was the essential pathway. Among the interaction network, the key node proteins in this network were p53 and transcription factor E2F1, respectively. CONCLUSIONS: 1D-SDS-PAGE coupled with RP-LC-MS/MS is a valuable resource to aid in the characterization of the proteome of RRD patients with PVR. Inflammation is the important pathologic process of PVR, while complement and coagulation cascade was the crucial pathway. p53 and E2F1 may be the new targets for successful treatment of RRD with PVR.

Indocyanine green-assisted internal limiting membrane peeling in macular hole surgery: a meta-analysis.

BACKGROUND: The opinion of application of indocyanine green (ICG) in the macular hole surgery was contradictory. Here we conducted a meta-analysis to evaluate the effect of in internal limiting membrane (ILM) peeling for macular hole surgery. METHODS AND FINDINGS: We searched electronic databases for comparative studies published before July 2012 of ILM peeling with and without ICG. Twenty-two studies including 1585 eyes were included. Visual acuity (VA) improvement, including the postoperative rate of ≥20/40 VA gained (OR, 0.65; 95% CI, 0.43 to 0.97; P = 0.033) and increased LogMAR (WMD, -0.09; 95% CI, -0.16 to -0.02; P = 0.011), was less in the ICG group. The risk of visual field defects was greater in the ICG group than in the non-ICG group. There was no significant difference in the rate of anatomical outcomes between ILM peeling procedures performed with and without ICG. RPE changes and other postoperative complications were not significantly different between the ICG and non-ICG groups. An additional analysis showed that the VA improvement of the ICG group was less than the non-ICG group only within the first year of follow up. A subgroup analysis showed that the rate of VA improvement was lower in the ICG group than in other adjuncts group. A higher rate of secondary closure and less VA improvement were observed in a high proportion (>0.1%) of the ICG group. A sensitivity analysis after the randomized-controlled trials were excluded from the meta-analysis demonstrated no differences compared with the overall results. CONCLUSIONS: This meta-analysis demonstrated that there is no evidence of clinical superiority in outcomes for ICG-assisted ILM peeling procedure over the non-ICG one. The toxicity of ICG should be considered when choosing the various staining methods.