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  • 1.

    【2hr】MR Volumetry of Lung Nodules: A Pilot Study

    包量

    机译 MR肺结节容积研究：一项初步研究
    摘要：Introduction: Computed tomography (CT) is currently the reference modality for the detection and follow-up of pulmonary nodules. While 2D measurements are commonly used in clinical practice to assess growth, increasingly 3D volume measurements are being recommended. The goal of this pilot study was to evaluate preliminarily the capabilities of 3D MRI using ultra-short echo time for lung nodule volumetry, as it would provide a radiation-free modality for this task.Material and Methods: Artificial nodules were manufactured out of Agar and measured using an ultra-short echo time MRI sequence. CT data were also acquired as a reference. Image segmentation was carried out using an algorithm based on signal intensity thresholding (SIT). For comparison purposes, we also performed manual slice by slice segmentation. Volumes obtained with MRI and CT were compared. Finally, the volumetry of a lung nodule was evaluated in one human subject in comparison with CT.Results: Using the SIT technique, minimal bias was observed between CT and MRI across the entire range of volumes (2%) with limits of agreement below 14%. Comparison of manually segmented MRI and CT resulted in a larger bias (8%) and wider limits of agreement (−23% to 40%). In vivo, nodule volume differed of <16% between modalities with the SIT technique.Conclusion: This pilot study showed very good concordance between CT and UTE-MRI to quantify lung nodule volumes, in both a phantom and human setting. Our results enhance the potential of MRI to quantify pulmonary nodule volume with similar performance to CT.
  • 2.

    【2hr】Diagnostic Value of FDG PET-CT Quantitative Parameters and Deauville-Like 5 Point-Scale in Predicting Malignancy of Focal Thyroid Incidentaloma

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    机译 FDG PET-CT定量参数和Deauville-Like 5点量表在预测局灶性甲状腺偶发瘤恶性程度中的诊断价值
    摘要：Objective: To evaluate the diagnostic value of FDG PET-CT metabolic parameters and Deauville-like 5 point-scale to predict malignancy in a population of patients presenting focal thyroid incidentaloma (fTI).Design: This retrospective study included 41 fTI, classified according to cytological and histological data as benign (BL) or malignant lesion (ML). FDG PET-CT semi-quantitative parameters (SUVmax, SUVmean, SUVpeak, MTV, TLG), tumor to liver SUVmean ratio (TLRmax and TLRmean), tumor to blood-pool SUVmean ratio (TBRmax and TBRmean) were calculated. Each fTI was also classified on a Deauville-like 5-point scale (DS) currently used in lymphoma. Comparison between BL and ML was performed for each parameter and a ROC analysis was conducted.Results: All quantitative PET metabolic parameters (SUV parameters, volume based parameters and SUV ratio) were higher in ML compared with BL, yet no significant difference was reported. fTI (uptake) malignancy rate according to DS grades 2, 3, 4, and 5 was, respectively, 25% (1 of 4), 28.6% (2 of 7), 8.3% (1 of 12), and 33.3% (6 of 18) with no significant difference between ML and BL groups. Results of ROC analysis showed that mean TBR had the highest AUC in our cohort (0.66 95%CI [0.41; 0.91]) with a cut-off value of 2.2. Specificity of MTV and TLG was 100% (cut-off values: MTV 9.6 ml, TLG 22.9 g) and their sensitivity was 30 and 40%, respectively.Conclusion: Our study did not highlight any FDG PET/CT parameter predictor of fTI malignancy.
  • 3.

    【2hr】Genetic Variation of Kallikrein-Kinin System and Related Genes in Patients With Hereditary Angioedema

    包量

    机译 遗传性血管性水肿患者激肽释放酶-激肽系统及相关基因的遗传变异
    摘要：Hereditary angioedema (HAE) is an autosomal dominant disease caused by C1-INH deficiency due to mutations in SERPING1 (C1-INH-HAE) in most of the cases, or by specific mutations in factor XII gene, F12 (F12-HAE). Identification of polymorphisms in the genes encoding proteins from key pathways driving HAE can help to understand how genetic diversity contributes to its phenotypic variability. Here, 15 genes related to the Kallikrein-Kinin System (KKS) were analyzed by next generation sequencing in 59 patients with C1-INH-HAE or F12-HAE from Brazil, Denmark and Spain, and 19 healthy relatives in a total of 31 families. We identified 211 variants, from which 23 occurred only in Danish subjects and 79 were found only in Brazilian individuals, resulting in 109/211 variations in common between European and Brazilian population in the HAE families analyzed. BDKRB2 and CPM presented a large number of variants in untranslated regions, 46/49 and 19/24, respectively; whereas ACE (n = 26), SERPING1 (n = 26), CPM (n = 24), and NOS3 (n = 16) genes presented the higher number of variants directly affecting amino acid sequence. Despite the large amount of variants identified, the lack of association between genotype and phenotype indicates that the modulation of HAE symptom requires a more complex regulation, probably involving pathways beyond the KKS, epigenetics and environmental factors. Considering the new HAE types recently described, molecules involved in the regulation of vasculature and in plasminogen activation become promising targets for future genetic studies.
  • 4.

    【2hr】Comparison of Characteristics of Neuropathic and Non-neuropathic Pruritus to Develop a Tool for the Diagnosis of Neuropathic Pruritus: The NP5

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    机译 比较神经性和非神经性瘙痒症的特征，以开发出诊断神经性瘙痒的工具：NP5
    摘要：The diagnosis of neuropathic pruritus (NP) may be difficult. The aim of this study was to compare the characteristics of both neuropathic pruritus and non-neuropathic pruritus (NNP) in order to elaborate a tool to help the diagnosis of NP without clinical examination. One hundred and seven patients were included: Fifty three in the NP group and Fifty four in the NNP group. In multiple regression, presence of twinges, absence of burning, worsening with activity, no worsening with stress, and relief with cold ambient temperature were independent factors that were associated with NP. A score of two criteria out of five was optimal to discriminate NP from NNP with a sensitivity of 76% and a specificity of 77%. Alloknesis, hyperknesis, or the ice cube test were not included because their evaluation is based on clinical examination. Future high-powered studies are needed to confirm the results of the present study.
  • 5.

    【2hr】Chromosomal Heterogeneity of the G-401 Rhabdoid Tumor Cell Line: Unusual Partial 7p Trisomy

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    机译 G-401横纹肌瘤细胞系的染色体异质性：异常部分7p三体性。
    摘要：Rhabdoid tumor is a very aggressive and hardly curable pediatric malignancy. It commonly starts in the kidneys but also can occur in the brain, liver, and other organs. The treatment of this tumor usually involves a combination of surgery, radiation, and chemotherapy. Because this tumor is rare, there is still limited experience with a defined standard of care. Cytogenetic analysis is an important routine method to monitor chromosomal aberrations. We have analyzed metaphases of the G-401 rhabdoid tumor cell line. In these cells we have observed metaphases with derivative chromosome 12 arising from partial trisomy 7p. With increasing passage number the numbers of metaphases having this derivative chromosome 12 were found to be higher. In passage number 2 only one metaphase had this pathological chromosome 12. By passage number 10 and passage number 15 about 25 and 95% of this derivative chromosome 12 were found, respectively. We were able to subclone G-401 cells by limiting dilutions and successfully separated cells having apparently normal karyotypes from cells having derivative chromosome 12. Using the cell proliferation assay we showed that clones possessing the derivative chromosome 12 grew more rapidly than clones with normal chromosomes. The cell cycle analysis confirmed this observation. Overall, in this study we describe for the first time a 7p triplication in a rare rhabdoid tumor of kidney. Both types of clones described in this study could be used as a preclinical model to study the involvement of partial chromosome 7 alterations in the development of rhabdoid tumors.
  • 6.

    【2hr】Cardiogeneticsbank@UZA: A Collection of DNA, Tissues, and Cell Lines as a Translational Tool

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    机译 Cardiogeneticsbank @ UZA：DNA，组织和细胞系的集合作为转化工具
    摘要：Cardiogeneticsbank@UZA is an academic hospital integrated biobank that collects aortic tissue, blood, cell lines (fibroblasts, vascular smooth muscle cells, peripheral blood mononuclear cells, and induced pluripotent stem cells), and DNA from patients with cardiogenetic disorders, for both diagnostic and research purposes. We adhere to a quality management system and have established standard protocols for the sampling and processing of all cardiogenetic patient related materials. Cardiogeneticsbank@UZA is embedded in the Biobanking and Biomolecular Resources Research Infrastructure Belgium (BBMRI.be) and samples from this biobank are available for commercial and academic researchers, through an established access procedure. Currently, the extremely valuable cardiogenetics collection consists of more than 8,700 DNA samples, 380 tissue samples, and 500 cell lines of 7,578 patients, and is linked with extensive clinical data. Some interesting potential research applications are discussed.
  • 7.

    【2hr】In silico Analysis of Gamma-Secretase-Complex Mutations in Hidradenitis Suppurativa Demonstrates Disease-Specific Substrate Recognition and Cleavage Alterations

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    机译 在化脓性汗腺炎中γ分泌酶复合突变的计算机分析表明特定疾病的基质识别和分裂改变。
    摘要：Background: Familial Hidradenitis Suppurativa and Familial Alzheimer's Disease are both associated with Gamma-Secretase Complex mutations; however, the two diseases are not epidemiologically associated. Understanding the molecular differences between the two diseases may aid in the development of hypotheses for differing pathogenesis and ultimately, targets for detection.Aims: To characterize the in silico structural and functional alterations to the Gamma Secretase Complex in documented mutations in Familial Hidradenitis Suppurativa, along with comparison of downstream substrate recognition and cleavage.Methods: In silico analysis of publicly available genomic data, assessment of protein structure and binding affinity using Swiss-model and Dynamut was undertaken. Differential Expression was expressed using Log Fold Change using the general framework for linear models in R. Differentially expressed genes (DEGs) were defined by FCH ≥1.5 or ≤−1.5 and false discovery rate (FDR ≤ 0.05).Results: Twenty three of 39 mutations in HS are degraded via nonsense mediated decay with altered substrate and binding affinity of substrates identified in the remaining mutations. Significant differential expression of ErbB4, SCNB1, and Tie1 in lesional skin was specific to Hidradenitis Suppurativa and EphB2, EPHB4, KCNE1, LRP6, MUSK, SDC3, Sortilin1 in blood specific to Familial Alzheimer's Disease.Discussion and Conclusions: We present the first in silico evidence as to the impact of documented mutations in Familial Hidradenitis Suppurativa. We also demonstrate unique substrate recognition and cleavage between Hidradenitis Suppurativa and Familial Alzheimer's Disease, providing a potential explanation as to why the two diseases do not occur within the same pedigree. These proteomic signatures may be a first step in identifying reliable biomarkers for Familial Hidradenitis Suppurativa.
  • 8.

    【2hr】Continued Chemotherapy After Concurrent Chemoradiotherapy Improves Treatment Outcomes for Unresectable Cutaneous Squamous Cell Carcinoma: An Analysis of 13 Cases

    包量

    机译 同期放化疗后继续化疗改善了不可切除的皮肤鳞状细胞癌的治疗效果：13例分析
    摘要：Background: There is no standard systemic therapy for unresectable cutaneous squamous cell carcinoma (ucSCC), although various chemotherapy regimens have been reported. In our department, concurrent chemoradiotherapy (CCRT) for ucSCC resulted in a 1-year survival rate similar to that of resectable cutaneous squamous cell carcinoma (cSCC). Treatment involves continued chemotherapy after CCRT. Here, we report the importance of continued chemotherapy after CCRT, based on treatment outcomes.Patients and Methods: We retrospectively evaluated 13 patients with ucSCC, assessing the overall survival, overall response rate (ORR), and disease control rate (DCR).Results: CCRT with continued chemotherapy resulted in an ORR of 84.6%, DCR of 92.3%, and 1-year survival rate of 75%. Of the 13 patients treated with CCRT with continued chemotherapy, 6 had no metastasis. The remaining 7 patients developed metastasis to other organs or lymph nodes beyond the regional lymph nodes, although most sites of metastasis were outside the irradiation area.Conclusion: We conclude that CCRT with continued chemotherapy was effective in treating the irradiation site (primary lesion and regional lymph nodes) and any organ metastasis, although, it is unclear for how long the treatment remains effective.
  • 9.

    【2hr】IgG Anti-high-Density Lipoproteins Antibodies Discriminate Between Arterial and Venous Events in Thrombotic Antiphospholipid Syndrome Patients

    包量

    机译 IgG抗高密度脂蛋白抗体可区分血栓性抗磷脂综合征患者的动脉和静脉事件
    摘要：Introduction: Recurrent thrombotic events are a hallmark of Antiphospholipid Syndrome (APS). However, biomarkers to identify if a patient with antiphospholipid antibodies (aPL) is at higher risk to develop an arterial or a venous event are lacking. Recently, the pathogenic role of anti-high-density lipoproteins antibodies (anti-HDL) in the occurrence of cardiovascular disease (CVD) in autoimmunity has emerged. The aim of the present study was to evaluate the presence of IgG anti-HDL antibodies in a cohort of thrombotic APS patients and to investigate their association with clinical outcomes.Methods: Serum levels of IgG anti-HDL antibodies, total IgG, and complete aPL profile were assessed in 60 APS patients and 80 healthy donors (HDs) by immunoassays.Results: Higher levels of IgG anti-HDL were found in APS patients compared to HDs (p < 0.001), even after correcting for total IgG levels (p < 0.001). No associations with treatments or traditional cardiovascular risk factors, except for smoking habit (p < 0.0001), were found. Patients who experienced at least one arterial event (n = 30) had significantly higher levels of anti-HDL antibodies when compared to patients with venous thrombosis (n = 30, p = 0.046), this difference being stronger when adjusting for total IgG (p = 0.007). Additionally, patients tested positive for antiphosphatidylserine/prothrombin (IgG/IgM) antibodies had significantly higher levels of anti-HDL antibodies (p = 0.045).Conclusions: Increased levels of IgG anti-HDL antibodies can be found in APS, mainly in patients with arterial thrombosis, independently of aPL antibodies and traditional risk factors. These findings point to a role of anti-HDL antibodies in APS and support their use as a potential biomarker for arterial thrombotic events.
  • 10.

    【2hr】Severe Refractory Paraneoplastic Mucous Membrane Pemphigoid Successfully Treated With Rituximab

    包量

    机译 利妥昔单抗成功治疗严重难治性副肿瘤黏膜膜天疱疮
    摘要：Mucous membrane pemphigoid (MMP) is a rare autoimmune bullous disease of the mucous membranes, which can cause irreversible scarring and is discussed to be associated with cancer, if laminin-332-autoantibodies are present. MMP with severe ocular and laryngeal involvement is difficult to treat and can be treatment-refractory to conventional immunosuppressant therapy. A 67-year-old man with a history of prostate cancer presented to our clinic with sore throat, intraoral bullae, odynophagia, dysphonia, exertional dyspnea, and erosions of the glans penis. Clinical examination confirmed a laryngo-pharyngitis with involvement of the epiglottis and bilateral symblepharon. Diagnostics comprising multiple biopsies, direct and indirect immunofluorescence, serology analysis, and immunoblotting confirmed the diagnosis of a paraneoplastic MMP by showing a subepithelial split in histology and the presence of anti-laminin-332-antibodies. Despite combined systemic treatment with prednisolone and either dapsone or azathioprine, a progress of the disease occurred leading to severe ocular and laryngeal complications. Two month after rituximab treatment, complete disease control was achieved. This case report shows a severe ocular and life threatening laryngeal involvement of therapy-refractory paraneoplastic MMP highlighting the importance of interdisciplinary management and difficulty of diagnosing MMP despite repeated diagnostic testing.
  • 11.

    【2hr】A Novel Homozygous Truncating Mutation in LAMB2 Gene in a Chinese Uyghur Patient With Severe Phenotype Pierson Syndrome

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    机译 中国维吾尔族严重表型皮尔森综合征患者LAMB2基因的新型纯合截断突变。
    摘要：Objective: Pierson syndrome (OMIM 609049) is a rare autosomal recessive disorder characterized by congenital nephrotic syndrome and complex ocular abnormalities. Severe renal symptoms had be associated with truncating mutations. Few Chinese patients from diverse ethnic background had been evaluated and reported with this syndrome. Here we report the first Uyghur patient with typical Pierson syndrome phenotypes and a novel pathogenic homozygous variant in LAMB2 gene.Method: A thirty-nine-day old Uyghur girl was born to consanguineous parents, the girl presented with general edema, severe hypotonia and bilateral microcoria. Laboratory tests revealed severe proteinuria, microscopic haematuria, hypoalbuminaemia. By the age of 74 days, she died of renal failure and respiratory infection. We detected on mutations of LAMB2 gene by the sanger sequencing.Result:Sanger sequencing detected a homozygous 2-bp deletion (c.2044_2045insTT/p.Cys682Phefs*13) in the exon 16 of LAMB2 gene. Both parents are heterozygous carriers.Conclusion: We reported the first Uyghur case of LAMB2 gene homozygous mutation leading to severe phenotype Pierson syndrome. The clinical presentation of the patient and the novel pathogenic variant detected in this patient added to the overall knowledge of this rare condition.
  • 12.

    【2hr】Acute Respiratory Distress Syndrome Associated With Clopidogrel in a Young Male Patient

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    机译 一名年轻男性患者的氯吡格雷相关的急性呼吸窘迫综合征
    摘要：Background: Clopidogrel is a commonly prescribed antiplatelet drug in patients with stents and histories of arterial vascular disease. It generally has a favorable side effect profile with increasing bleeding risk as the main concern as an adverse event.Case Presentation: A 19-year-old previously healthy male presented to the neurological intensive care unit with a subarachnoid hemorrhage requiring a flow diverting stent to secure the aneurysm. The patient was stable for 2 weeks and had no changes to management or medication within 48 h of antiplatelet therapy. Within hours of first-time dosing of clopidogrel, the patient experienced a syncopal episode and dyspnea. He was difficult to arouse and using accessory muscles to breath with an otherwise benign exam. He was hypoxic with bibasilar crackles requiring bilevel positive airway pressure (BiPap). Imaging showed bilateral pulmonary edema and he was diagnosed with moderate acute respiratory distress syndrome (ARDS). Infectious, cardiogenic, and contrast-induced ARDS were ruled out. Upon cessation of clopidogrel, his pulmonary function and mental status improved.Conclusions: This is the first reported case of a young and immunocompetent patient's severe pulmonary edema leading to acute respiratory distress syndrome in association with first- time dosing of clopidogrel.
  • 13.

    【2hr】Extracorporeal Membrane Oxygenation in Severe Acute Eosinophilic Pneumonia

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    机译 严重急性嗜酸性粒细胞性肺炎的体外膜氧合
    摘要：Acute Eosinophilic Pneumonia (AEP) is a potentially fatal cause of hypoxemic respiratory failure characterized by fever, diffuse bilateral pulmonary infiltrates, and pulmonary eosinophilia. Shown to be associated with a number of environmental exposures and lifestyle choices, AEP has a good prognosis when diagnosed early and treated with corticosteroids. In this clinical case report, we detail the presentation, evaluation, diagnosis, and management of a 40-year old male who presented to the emergency department with dyspnea, chills, and diaphoresis. He had a history of pulmonary embolism 8 years prior but was otherwise healthy, though he had re-started smoking cigarettes a week prior to presentation. Initial chest CT scan revealed widespread mixed groundglass and solid airspace opacities; over the next 12 hours, he rapidly decompensated and after not responding to other invasive mechanical ventilation, was emergently cannulated for veno-venous extracorporeal membrane oxygenation (V-V ECMO). Bronchoalveolar lavage later revealed pulmonary eosinophilia, and after an infectious workup was negative, a diagnosis of AEP was reached and the patient was started on corticosteroids. To our knowledge, this is one of few published cases of AEP requiring V-V ECMO for clinical stabilization, highlighting the utility of this treatment modality in severe disease.
  • 14.

    【2hr】Hereditary Angioedema-Associated Acute Pancreatitis in C1-Inhibitor Deficient and Normal C1-Inhibitor Patients: Case Reports and Literature Review

    包量

    机译 C1抑制剂缺乏和正常C1抑制剂患者的遗传性血管性水肿相关性急性胰腺炎：病例报告和文献复习
    摘要：Abdominal pain due to intestinal swellings is one of the most common manifestations in hereditary angioedema (HAE). Bowel swellings can cause severe abdominal pain, nausea, vomiting, and diarrhea, which may lead to misdiagnosis of gastrointestinal disorders. In rare cases, HAE abdominal attacks can be accompanied by acute pancreatitis. Here, we report 3 patients with HAE and acute pancreatitis and present a literature review of similar cases. Patients with confirmed diagnosis of HAE secondary to C1-inhibitor (C1-INH) deficiency (n = 2) and HAE with normal C1-INH and F12 mutation (F12-HAE) (n = 1) were included. Pancreatitis was diagnosed based on clinical symptoms and high lipase and amylase levels. Three HAE patients were diagnosed with acute pancreatitis based on increased amylase levels during severe abdominal swelling episodes. Two were previously diagnosed with HAE type I and one with F12-HAE. Pancreatitis was efficiently treated in two patients using Icatibant, with pain relief within hours. When conservatively treated, pancreatitis pain took longer time to resolve. Eighteen pancreatitis cases in HAE with C1-INH deficiency were previously reported and none in F12-HAE. Most patients (12/18) underwent invasive procedures and/or diagnostic methods. Although rare, severe abdominal HAE attacks could cause pancreatitis; HAE-specific treatments may be efficient for HAE-associated pancreatitis. HAE should be considered as a differential diagnosis of acute idiopathic pancreatitis. To our knowledge, this is the first report of HAE-associated pancreatitis in a F12-HAE patient treated with Icatibant.
  • 15.

    【2hr】Lazarus Effect of High Dose Corticosteroids in a Patient With West Nile Virus Encephalitis: A Coincidence or a Clue?

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    机译 高剂量皮质类固醇对西尼罗河病毒性脑炎患者的拉撒效应：是巧合还是线索？
    摘要：West Nile virus (WNV) causes severe neuroinvasive disease in humans characterized by meningitis, encephalitis, and acute flaccid paralysis (poliomyelitis variant). In neuroinvasive disease, WNV infection of neurons resulting in neuronal loss is generally presumed to be the anatomical substrate for the high morbidity and mortality. However, on a molecular level, WNV infection also results in a significant upregulation of important proinflammatory molecules that have been reported to promote neuroinflammation and cytotoxicity. Currently, there is no specific treatment for the neurological complications of WNV infection. We present a 71-year-old woman who developed WNV infection that rapidly progressed to severe generalized weakness and encephalitis manifesting with bulbar signs (dysphagia, dysarthria) and persistent delirium and stupor. Consciousness remained impaired for 9 days and then she received a 5-day course of high-dose intravenous methylprednisolone (1,000 mg daily). After the first day, voluntary movement and spontaneous eye-opening increased and by the end of the second day, she was awake and responding to commands. Thereafter, she remained awake and responsive. Although the rapid improvement from stupor to wakefulness following treatment with an anti-inflammatory immunosuppressant could merely be coincidence, since these observations are of one patient, it may also provide a clue that in some cases of WNV neuroinvasive disease a post-infectious pro-inflammatory state, rather than neuronal loss, may also contribute to morbidity. Further clinical trials are warranted to determine if high dose corticosteroids and other drugs that can alter this neuro-inflammatory cascade may be potentially beneficial in the treatment of WNV neuroinvasive disease.
  • 16.

    【2hr】Multiple Dermal Abscesses by Trichophyton rubrum in an Immunocompromised Patient

    包量

    机译 免疫受损患者的毛癣菌多发性皮肤脓肿
    摘要：We report the case of a 52-year-old man who presented with a 10 year history of multiple nodules with purulent drainage on the upper extremities. Several attempts of treatment with oral antibiotics had been unsuccessful. A skin biopsy specimen showed a dermal abscess with branched septate hyphae. A mycological culture of pus and of the biopsy specimen revealed Trichophyton rubrum. Deeper dermatophytosis presenting as dermal abscesses is a rare disease which occurs normally in immunocompromised conditions. Our patient was on immunosuppressive therapy with methylprednisolone and azathioprine because of inflammatory demyelinating polyneuropathy and presented with extensive abscesses. In cases of dermal abscesses it is important to not only consider bacterial but also fungal infections as underlying cause.
  • 17.

    【2hr】Successful Treatment of Unresectable Advanced Melanoma by Administration of Nivolumab With Ipilimumab Before Primary Tumor Resection

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    机译 在原发性肿瘤切除术前给予依普利单抗联合Nivolumab成功治疗无法切除的晚期黑色素瘤
    摘要：Ipilimumab, in combination with nivolumab, is one of the promising drugs that enhance the anti-tumor immune response of patients with advanced melanoma. Since the co-administration of nivolumab with ipilimumab in the neoadjuvant setting expands melanoma-reactive T cells at the primary site of melanoma and has a high rate of histological complete response, the pre-surgical administration of this combination could be the optimal therapy for unresectable advanced melanoma. In this report, a case of unresectable advanced melanoma treated successfully with administration of nivolumab with ipilimumab before primary tumor resection is presented. In addition, CD8+ T cells increased among the tumor-infiltrating lymphocytes that were surrounding melanoma cells and caspase 3+ cells. The present case suggests that pre-surgical administration of nivolumab with ipilimumab could be the optimal therapy for the treatment of unresectable advanced melanoma.
  • 18.

    【2hr】Variations in Vaginal, Penile, and Oral Microbiota After Sexual Intercourse: A Case Report

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    机译 性交后阴道，阴茎和口腔菌群的变化：病例报告
    摘要：Background: Bacterial vaginosis is the most common infection in women and it has been proved that dysbiosis of vaginal microbiota can promote the infectious status. This case report shows the effect of oral and vaginal sex over the microbiota of a heterosexual couple who reported repeated problems of vaginal and oral infections after sexual intercourse.Case Presentation: A woman (32) reported to have vaginal infections and gingivitis after she had started a relationship with a man (34) and associated them with unprotected sex. No treatments successfully removed the problem and it repeated every time they had sexual encounters. Vaginal, penile and oral swabs were collected before and after sexual encounters in order to analyze changes in the respective microbiotas. DNA was extracted from all samples and the bacterial 16S rRNA gene was sequenced using Illumina MiSeq.Conclusions: Lactobacillus occupied the great majority of the vaginal microbiota in all scenarios except after unprotected sex, which caused a bacterial dysbiosis that lasted at least for a week. Similarly, the penile microbiota changed significantly after unprotected sexual relationships. Interestingly, both oral and vaginal sex increased the abundance of Lactobacillus in the male oral and penile microbiota, respectively. In conclusion, unprotected sexual intercourse influenced the genital microbiota in the couple studied and future studies with larger sample sizes should study if sex may be a factor promoting vaginal infection through dysbiosis and hampered protection by the resident microbiota.
  • 19.

    【2hr】Next-Generation Sequencing for the Diagnosis of Challenging Culture-Negative Endocarditis

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    机译 具有挑战性的培养阴性心内膜炎的下一代测序
    摘要：Diagnosis of culture-negative infective endocarditis usually implies indirect pathogen identification by serologic or molecular techniques. Clinical metagenomics, relying on next-generation sequencing (NGS) is an emerging approach that allows pathogen identification in challenging situations, as evidenced by a clinical case. We sequenced the DNA extracted from the surgically-removed frozen valve tissue from a patient with suspected infective endocarditis with negative blood and valve cultures. Mapping of the sequence reads against reference genomic sequences, a 16S rRNA gene database and clade-specific marker genes suggested an infection caused by Cardiobacterium hominis.
  • 20.

    【2hr】Rheopheresis for Digital Ulcers and Raynaud's Phenomenon in Systemic Sclerosis Refractory to Conventional Treatments

    包量

    机译 常规疗法难治的系统性硬化症中数字溃疡和雷诺现象的流变疗法
    摘要：Raynaud's phenomenon (RP) is almost universally present in patients with Systemic Sclerosis (SSc). RP represents a generalized vasculopathy and potentially lead to digital ulcers (DU), which may be complicated by superinfection, tissue necrosis, and limb loss. We report the analysis of an extracorporeal procedure in a 36-year-old female patient with diffuse SSc with refractory RP and DU despite treatment with diltiazem, candesartan, sildenafil, and intravenous iloprost. We performed rheopheresis (RheoP), a variant of double-filtration plasmapheresis, as a potential new treatment option for refractory patients despite optimal medical therapy. We performed two RheoP per week every 4 weeks for a total of 3 months. Clinical improvement in DU healing occurred with no adverse events directly related to the treatment. While there was no reduction in the number of Raynaud attacks with RheoP, a significant reduction of the duration of attacks from a median of 15 (5–45, 95% CI 10–15) to 7 (3–30, 95% CI 6–10) minutes with an improvement of the Raynaud Condition Score (RCS) improved from 4 to 2. In conclusion, RheoP is a feasible and potentially beneficial treatment modality in patients with refractory RP and DU. We propose that RheoP should be investigated in a larger number of patients in a clinical trial setting.
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