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Coronavirus disease 2019 (COVID-19) is a novel and highly contagious disease caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Older adults and patients with comorbidities and immunosuppressive conditions may experience severe signs and symptoms that can lead to death. This case series assesses the clinical course, imaging features, and outcomes for 12 patients with COVID-19 and a history of kidney transplantation. Patients were evaluated for symptoms, laboratory data, imaging findings, and outcomes from February 2020 to April 2020. Fever, cough, and dyspnea were the most common clinical symptoms, noted in 75% (nine/12), 75% (nine/12), and 41.7% (five/12) of the patients, respectively. Most of the patients had a normal white blood cell count, while 33.3% (four/12) had leukopenia and 8.3% (one/12) had leukocytosis. A combination of consolidation and ground glass opacity was the most predominant (75%) pattern of lung involvement on computed tomography (CT). Eight patients died of severe COVID-19 pneumonia and acute respiratory distress syndrome and four were discharged. All recovered cases had a unilateral peripheral pattern of involvement limited to only one zone on initial chest CT. It seems that CT imaging has an important role in predicting COVID-19 outcomes for solid organ transplant recipients. Future studies with long-term follow up and more cases are needed to elucidate COVID-19 diagnosis, outcome, and management strategies for these patients.

Giant axonal neuropathy (GAN) is a very rare autosomal recessive disorder characterized by abnormally large and dysfunctional neuronal axons. Mutations in the GAN gene have been identified as the cause of this disorder. In this report, we performed a detailed phenotypic assessment of a Chinese patient with GAN. An array-based exon capture test and targeted next-generation sequencing were used to detect the suspected mutation sites. Compound heterozygous mutations of p.S79L (c.236C > T) in the BTB domain and p.T489S (c.1466C > G) in the kelch domain were identified in the proband’s genome. S79L was a known mutation, and T489S was reported for the first time. The p.S79L and p.T489S were confirmed in the proband’s mother and father, respectively. Both mutations were located in highly conserved regions and affected the predicted protein crystal structures. The proband’s sural biopsy revealed the classical GAN phenotype of swollen axons filled with closely packed neurofilaments. The combined application of the next-generation sequencing platform and bioinformatics analyses was an effective method for diagnosing GAN. The novel compound mutations of S79L and T489S in the GAN gene were likely the cause of the patient’s GAN symptoms. Our findings enrich the spectrum of mutations associated with this rare type of axonopathy.

Objective: Hashimoto’s thyroiditis (HT) is a common autoimmune thyroid disorder that frequently evolves from asymptomatic, T-cell mediated chronic inflammation toward overt hypothyroidism. Previously, we have demonstrated a role for T-bet, a T helper 1/CD8+ T cell transcription factor (TF), and FoxP3, a regulatory T cell TF, in disease progression and severity, but the basis behind their altered mRNA expression remains unknown. In this study, we aimed to leverage the role for microRNAs, representing negative transcriptional regulators, across the spectrum of HT clinical presentations using the same, well-characterized RNA sample cohort. Method: Ten hypothyroid, untreated patients (hypoHT), 10 hypothyroid cases rendered euthyroid by l-thyroxine therapy (substHT), 11 spontaneously euthyroid HT subjects (euHT), and 10 healthy controls (ctrl) were probed for three candidate immunoregulatory miRNA (miR-9-5p, miR- 29a-3p, and miR-210-3p) using quantitative real- time PCR measurements. Data were normalized to U6snRNA and fold difference in expression calculated by the efficiency corrected 2−ΔΔCt model. Results: Compared to healthy controls, peripheral blood (PB) T cells of HT patients exhibited significantly diminished miR-29a-3p expression levels [median expression levels (IQR), HT vs CTRL, 0.62 (0.44–1.01) vs 1.373 (0.63–2.7), P = 0.046], and a similar, but not significant decline in miR-210-3p abundance [HT vs CTRL, 0.64 (0.39–1.31) vs 1.2 (0.5–2.56), P = 0.24, Wilcoxon test]. A significant inverse correlation was observed between the two differentially expressed transcripts, T-bet mRNA and miR-29a-3p. Moreover, altered miR-29a-3p/T-bet expression in T cells of untreated HT patients was related to low serum FT4, high serum thyrotropin, and decreased thyroid volumes. Of note, miR-210-3p expression was positively correlated to HIF1α, and inversely to FoxP3 mRNA levels, but no evidence of differential expression for any of these miRNA–mRNA pairs was observed. Finally, miR-9-5p expression levels were no different in HT vs control comparisons, or related to clinicopathological features. Conclusion: T cell miR-29a-3p is downregulated in HT patients and associated with clinical and biochemical parameters of progressive thyroid injury, plausibly subsequent to altered control of T-bet expression in PB T cells. As such miR- 29a-3p/T-bet axis should be further explored as a biomarker or as a plausible target for therapeutic interventions in HT.

К аутоиммунным заболеваниям печени относят аутоиммунный гепатит (АИГ), первичный билиарный цирроз/холангит (ПБХ), первичный склерозирующий холангит (ПСХ) и аутоиммунные холангиопатии. Они являются редкими, недостаточно изученными, поэтому сложными для понимания и ведения даже узкопрофильными специалистами.Цель работы – предоставить современное представление об аутоиммунных заболеваниях печени и их особенностях.Важно четко различать АИГ, ПБХ, ПСХ. Эпидемиологические данные свидетельствуют об их низкой распространенности, но отмечается ее рост. Поражают лиц молодого и среднего возраста, АИГ и ПБХ диагностируют чаще женщин, ПХ – у мужчин. Этиологические факторы остаются неизвестными, рассматривается роль вирусно-бактериальных, токсических, медикаментозных агентов, которые изменяют иммунную систему с формированием аутоантител. Имеют значение генетические факторы.Диагностика основывается на характерных признаках. АИГ может протекать как острый или хронический гепатит, цирроз или фульминантная печеночно-клеточная недостаточность, длительно может быть бессимптомным. Для ПБХ и ПСХ характерна клиника холестаза – кожный зуд, желтуха, изменения кожи. На поздних стадиях разворачивается картина цирроза печени. В печеночных пробах при АИГ преобладает цитолиз, достигающий высоких значений, при ПБХ и ПСХ – холестаз с высокими щелочной фосфатазой и ГГТП.Диагностика по маркерам имеет решающее значение в нашей стране. В пользу АИГ свидетельствуют обнаружение ANA, SMA, анти-LKM, анти-SLA, анти-LP анти-LC1, ASGP-R, повышение IgG. Высокоспецифичным маркером ПБХ является АМА-М2, при ПСХ могут определяться p-ANCA.Среди визуализирующих методов гепатобилиарной системы выделены МРХПГ как точный метод оценки протоковой системы при ПСХ и эластограмму печени для установления степени фиброза при ее различных заболеваниях.Лечение аутоиммунных заболеваний печени, согласно последним рекомендациям EASL, включает иммуносупрессивную терапию гормонами, азатиоприном, другими цитостатиками, УДХК. Поскольку данные доказательной медицины лимитированы, считается, что в лечении таких больных перевешивает мнение врача-эксперта. Приведены клинические примеры, демонстрирующие особенности ведения этих больных.Выводы. Диагностика и лечение аутоиммунных заболеваний печени – сложный процесс. В этом значительно помогают современные рекомендации, вместе с тем имеют значение клинический опыт врача и индивидуальные данные больного., Autoimmune hepatitis (AIH), primary biliary cirrhosis/cholangitis (PBC), primary sclerosing cholangitis (PSC) and autoimmune cholangiopaties are the autoimmune liver diseases. These diseases are rare and remain under-explored, therefore difficult for understanding and conducting even by specialists. Aim. To provide a comprehensively modern view of autoimmune liver diseases and their features. It is important to clearly distinguish AIG, PBH, and PSC between each other. Epidemiological data indicate low prevalence of these diseases, but its growth is noted. Most of the patients are young and middle age, prevalence of the AIH and PBC is higher in women, for PSC - in men. Etiologic factors remain unknown; the role of viral-bacterial, toxic, drugs that change the immune system with forming of autoantibodies is examined. Genetic factors also may play role in pathogenesis of these diseases. Diagnostics of autoimmune liver diseases are based on specific signs. AIH can proceed as acute or chronic hepatitis, cirrhosis or fulminant hepatic-cellular insufficiency, but also can be asymptomatic for a long time. For PBC and PSC, the clinic of cholestasis is characterized by skin itch, jaundice, skin changes. In later stages, a picture of cirrhosis develops. Hepatic tests in patients with AIH are characterized by predominance of cytolysis that can reach high values, and for PBC and PSC – cholestasis with high alkaline phosphatase and GGTP.Diagnostics with specific markers of autoimmune liver diseases are crucial for our country. AIH is characterized by detection of ANA, SMA, anti-LKM, anti-SLA, anti-LP anti-LC1, ASGP-R, and increased level of IgG. A highly specific PBC marker is AMA-M2, while p-ANCA can be determined in PSC.Among the visualizing methods of the hepatobiliary system, MRCP was identified as an accurate method for evaluating the duct system in PSC and liver elastography for evaluating the degree of fibrosis.Treatment of autoimmune liver diseases, according to the latest EASL recommendations, includes immunosuppressive therapy with hormones, azathioprine, other cytostatics, UDCA. Since the data of evidence-based medicine are limited, it is believed that an expert opinion can be crucial for the treatment of such patients. Clinical examples showing the features of management of autoimmune liver diseases are given in this article.Conclusions. Diagnosis and treatment of autoimmune liver diseases are a complex process. In this case, the latest modern recommendations can considerably help, at the same time, the clinical experience of the doctor and the patient’s individual data still matter., До аутоімунних захворювань печінки належать аутоімунний гепатит (АІГ), первинний біліарний цироз/холангіт (ПБХ), первинний склерозуючий холангіт (ПСХ) та аутоімунні холангіопатії. Вони є рідкими, недостатньо вивченими, а отже складними для розуміння та ведення навіть вузькопрофільними спеціалістами.Мета роботи – надати сучасне уявлення про аутоімунні захворювання печінки та їхні особливості.Важливо розрізняти АІГ, ПБХ, ПСХ. Епідеміологічні дані свідчать про їхню низьку поширеність, але спостерігають її збільшення. Уражають осіб молодого та середнього віку, АІГ і ПБХ діагностують частіше в жінок, ПСХ – у чоловіків. Етіологічні чинники залишаються невідомими, розглядається роль вірусно-бактеріальних, токсичних, медикаментозних агентів, що змінюють імунну систему з формуванням аутоантитіл. Мають значення генетичні фактори.Діагностика базується на характерних ознаках. АІГ може перебігати як гострий чи хронічний гепатит, цироз або фульмінантна печінково-клітинна недостатність, тривало може бути безсимптомним. Для ПБХ і ПСХ характерна клініка холестазу – шкірний свербіж, жовтяниця, зміни шкіри. На пізніх стадіях розгортається картина цирозу печінки. У печінкових пробах при АІГ переважає цитоліз, який сягає великих значень, при ПБХ та ПСХ – холестаз із високими лужною фосфатазою та ГГТП.Діагностика за маркерами має провідне значення в нашій країні. На користь АІГ свідчить визначення ANA, SMA, анти-LKM, анти-SLA, анти-LP анти-LC1, ASGP-R, підвищення IgG. Високоспецифічним маркером ПБХ є АМА-М2, при ПСХ можуть виявлятись p-ANCA.Серед візуалізуючих методів гепатобіліарної системи виділено МРХПГ як точний метод оцінювання протокової системи при ПСХ та еластограму печінки для визначення ступеня фіброзу при її різних захворюваннях.Лікування аутоімунних захворювань печінки, згідно з останніми рекомендаціями EASL, включає імуносупресивну терапію гормонами, азатіоприном, іншими цитостатиками, УДХК. Оскільки дані доказової медицини лімітовані, вважається, що в лікуванні таких хворих має перевагу думка лікаря-експерта. Наведено клінічні приклади, що наочно демонструють особливості ведення цих хворих.Висновки. Діагностика та лікування аутоімунних захворювань печінки є складним процесом. У цьому значно допомагають сучасні рекомендації, поряд з тим мають значення клінічний досвід лікаря та індивідуальні дані конкретного хворого.

目的 探讨母细胞性浆细胞样树突细胞肿瘤（BPDCN）的临床特征、治疗和预后。 方法 回顾性分析2008年1月至2016年5月北京协和医院确诊的6例BPDCN患者的临床资料。 结果 6例患者起病时均有皮肤受累，常见表现包括骨髓受累（5例）、淋巴结肿大（4例）、脾大（4例）和肝大（3例）。皮肤外的结外器官受累包括乳腺、上颌窦、椎体和中枢神经系统各1例。肿瘤细胞特征性的免疫表型CD4、CD56、CD123均为阳性。治疗均采用急性淋巴细胞白血病样方案，4例达到完全缓解。中位随访9.5（7~37）个月，中位无进展生存期7个月，中位总生存期9个月。死亡3例，均在诊断后1年内死于原发病复发或进展。 结论 BPDCN侵袭性强，常以皮肤受累为首发症状，骨髓受累、淋巴结和肝脾大较为常见；特征性免疫标志包括CD4、CD56和CD123；目前缺乏有效、标准的治疗方案，预后不良。

目的 分析高嗜酸粒细胞综合征(HES)的临床特征和长期疗效。 方法 回顾性分析接受糖皮质激素单药治疗的60例初诊HES患者的临床资料，通过随访获得患者生存情况及死亡原因。 结果 全部60例HES患者中，男45例，女15例，中位年龄38(11~80)岁。常见受累器官依次为皮肤(55.0%)、胃肠道(40.0%)、肺(35.0%)、心脏(13.3%)、血管(10.0%)和神经肌肉(10.0%)。单器官受累27例(45.0%)，2个器官受累22例(36.7%)，2个以上器官受累11例(18.3%)。糖皮质激素中位诱导治疗剂量相当于泼尼松30(15~60)mg/d，治疗总有效率[完全缓解(CR)+部分缓解(PR)]为88.3%(53/60)。联合或更换其他药物后总有效率提升至93.3%(56/60)。38例治疗有效患者至随访截止时仍接受糖皮质激素单药(33例)或联合(5例)维持治疗，糖皮质激素的中位治疗时间为51(5~92)个月，中位维持剂量相当于泼尼松5(1.25~40)mg/d。20例患者因疾病缓解后依从性差或治疗无效停用糖皮质激素。HES患者5年总体生存率为(90.0±4.3)%，主要死亡原因为心脏功能异常。 结论 HES对糖皮质激素治疗敏感，多数疗效欠佳的患者可以通过联合用药改善疗效。心脏功能异常是患者的主要死亡原因。

To investigate the morbidity, treatment outcomes and prognosis of 35 therapy-related hematological neoplasms patients.A total of 35 cases of therapy-related hematological neoplasms were examined genetically and immunologically using flow cytometry, karyotype analysis and FISH, and their clinical data were retrospective analyzed and literatures were reviewed.Among 35 patients, there were 20 cases of therapy-related acute myeloid leukemia (t-AML), 4 cases of therapy-related acute lymphoblastic leukemia (t-ALL), 1 case of acute mixed leukemia, therapy-related non-hodgkin' s lymphoma (t-NHL) in 8 cases and myelodysplastic syndrome (t-MDS) in 2 cases. The median onset of t-HN was 29(16-90) months, the median OS of t-HN was 14(1-60) months, and 3 years of OS was 17.1%. Among therapy-related acute leukemia (t-AL) patients, 40% (10/25) patients had combined complex karyotype, 36% (9/25) patients with MLL gene rearrangement, 12% (3/25) patients with combined AML/ETO fusion gene, 1 case with NPM1 point mutation and 1 case with P16 gene deletion.Therapy-related hematological neoplasms had a worse prognosis.

Peptidomics involves the comprehensive analysis of the peptide content of a certain cell, organ, body fluid, or organism. Per E. Andren and colleagues at Uppsala University and the Karolinska Institutet (both in Sweden) describe neuropeptidomics approaches in brain lysates and tissue sections to study peptide expression in disease models and to identify potentially biologically active neuropeptides.

To analyze the clinical features and prognosis of acute leukemia patients with the mixed lineage leukemia（MLL）gene rearrangements AF10 positive.6 cases with MLL-AF10 positive were analyzed retrospectively, related literatures were reviewed to clarify MLL-AF10 patients'clinical features and prognosis.The median age of 6 cases was 19.5 years old, 5 patients with fever onset, the onset white blood cells of 4 patients were less than 10×10⁹/L. 5 cases were as M₅ and 1 case M₄ according to FAB classification, the level of fusion gene（RQ-PCR）was 0.23%-22.60% when diagnosed, 4 cases had concomitant WT1 gene mutation, flow cytometry disclosed myeloid phenotype. Of 5 evaluated patients achieved the first complete remission after conventional chemotherapy, 2 cases of complex karyotype died, one case died of sepsis in induction, another died from failing of transplantation. 4 out of 5 transplant recipients gained long term survival.The MLL-AF10 positive patients were mostly young men, the majority FAB classification was M5 or M4, often onset with fever, low white blood cells and low level of fusion gene, usually associated with WT1 mutation. Conventional chemotherapy produced a high response rate, but easy to relapse, while the complex karyotype had a poor prognosis, allo-HSCT may have the potential to improve the prognosis of MLL-AF10 positive patients.

To report an acute promyelocytic leukaemia (APL) case with translocation of rob (13;21) t(15;17) (q22;q21) and review its clinical and laboratory characteristics.Based on routine karyotype analysis and bone marrow morphology, we further used double color double fluorescent in situ hybridization (DCDF-FISH) and reverse transcriptase PCR (RT-PCR) to examine the patient's abnormities on cytogenetic and molecular biology, and reveal the clinical characteristics of this rare translocation also from the related literatures.The clinical manifestation and bone marrow morphology examination of this patient were in accordance with pathologic feature of APL. On first visit, immunophenotyping analysis showed positive myeloid markers. Through R-banding, the patient's karyotype was confirmed as 45, XX, rob(13;21) t(15;17) (q22;q21) [6]/45, XX, rob(13;21) [14]. FISH results showed that 68.9% cells were typical t(15;17) pattern. The positive rates of fusion gene of PML-RARα detected by RT-PCR was 25.8%. Patient was treated by induction and consolidation therapy, the karyotype was 45, XX, rob(13;21 )[20] after complete remission. The positive rate of fusion gene of PML-RARα by FISH and its level were 2.5% and 0.003% respectively.APL with rob (13;21) t(15;17) (q22;q21) was very rare, which was accorded with clinical and laboratory characteristics of APL. The value of chromosome abnormality as a prognostic marker in APL needs to be further observed..

To explore the clinical and survival significance of CD20 positive adult patients with B-lineage acute lymphoblastic leukemia (B-ALL).The clinical features and survival of 168 adult patients with B-ALL diagnosed and treated in our department from May 2007 to July 2011 were analyzed retrospectively, 58 expressed CD20 and 110 not.The sex, distribution of age, anemia, thrombocytopenia, infiltration of liver, spleen and lymph nodes, the expression of myeloid lineage marker, incidence of Ph chromosome, complete remission within 4 weeks showed no significant differences in CD20 positive and negative groups (P0.05); median white blood cell count at diagnosis and the rate of patients with high white blood cell count in CD20 positive group were 19.2×10⁹/L and 37.9% respectively, which were significantly higher than those of 6.93 × 10⁹/L and 20.9% in CD20 negative group (P0.05); cumulative incidence of relapse between two groups showed significant difference (P0.05); multivariable analysis for overall survival and progress-free survival identified CD20 positivity as independent predictor.The expression of CD20 in adult patients with B-ALL appeared to be associated with high white blood cell count and poor prognosis.

OBJECTIVES The aim of this study was to assess the quality of life (QoL) of patients with multiple sclerosis (MS), and to investigate the effects of characteristics of MS such as disease course, severity, and relapses on patients’ QoL. METHODS This was a cross-sectional study, in which 171 patients were enrolled. Health-related QoL was assessed using the Persian version of the Multiple Sclerosis Quality of Life-54 questionnaire. To measure patients’ disability status, we used the Expanded Disability Status Scale. Other variables included in the study were disease course and relapses of the disease. RESULTS The average scores for patients’ physical and mental QoL were 60.9±22.3 and 59.5±21.4, respectively. In a bivariate analysis, disease course, severity of the disease, and relapses were significantly associated with the physical and mental health composite scores. In a hierarchal regression analysis, disease course, severity of the disease, and relapses were responsible for 38 and 16% of the variance in physical and mental QoL, respectively. It was also observed that relapses were a strong predictor of both physical and mental QoL. CONCLUSIONS Our results showed that disease characteristics significantly affected both dimensions of QoL. It is therefore suggested that health care providers should be aware of these characteristics of MS to more successfully improve MS patients’ QoL.

SUMMARY Ventilator-associated pneumonia (VAP) is the second most common hospital-acquired infection among pediatric intensive care unit (ICU) patients. Empiric therapy for VAP accounts for approximately 50% of antibiotic use in pediatric ICUs. VAP is associated with an excess of 3 days of mechanical ventilation among pediatric cardiothoracic surgery patients. The attributable mortality and excess length of ICU stay for patients with VAP have not been defined in matched case control studies. VAP is associated with an estimated $30,000 in attributable cost. Surveillance for VAP is complex and usually performed using clinical definitions established by the CDC. Invasive testing via bronchoalveolar lavage increases the sensitivity and specificity of the diagnosis. The pathogenesis in children is poorly understood, but several prospective cohort studies suggest that aspiration and immunodeficiency are risk factors. Educational interventions and efforts to improve adherence to hand hygiene for children have been associated with decreased VAP rates. Studies of antibiotic cycling in pediatric patients have not consistently shown this measure to prevent colonization with multidrug-resistant gram-negative rods. More consistent and precise approaches to the diagnosis of pediatric VAP are needed to better define the attributable morbidity and mortality, pathophysiology, and appropriate interventions to prevent this disease.

Disease shows its dual nature: it carries suffering and pain, but also means trespassing the sluggish limits of healthy life. This trespassing confirms the distance separating man from nature and, at the same time, confirms man's spirituality. Nietzsche's disease and work support this interpretation, so precisely expressed by Thomas Mann in his novel Doctor Faustus: disease contains the diabolus of human biology and human spirituality.