Genomic Analysis Reveals Distinct Subtypes in Two Rare Cases of Primary Ovarian Lymphoma

Primary (localized) non-Hodgkin lymphoma (NHL) of the ovary is extremely rare; only a few cases have been reported in the literature. We report two cases of primary ovarian lymphoma (POL), one involving bilateral ovaries in a 15-year-old girl and other involving one ovary in a 5-year-old girl. This report describes detailed clinical, histopathological, and imaging findings, along with the review of literature of primary diffuse large B-cell lymphoma (DLBCL) arising from an ovary. In addition, we describe findings of targeted capture panel sequencing on both tumors and identify the major genetic mutations that are recurrently mutated in pan-cancers. Compared to the genomic mutation features of major subtypes of DLBCL, we distinguish that each POL belongs to distinctive subtypes, GCB (germinal center B-cell subtype) DLBCL and ABC (activated B-cell subtype) DLBCL, respectively. The findings from the genomic analysis may help to understand the pathogenesis of POL and to guide potential targeted therapy in the future.     

Inflammatory features of melasma lesions in Asian skin

Melasma is triggered by various factors including ultraviolet radiation and estrogen; however, its pathogenesis is unclear. To investigate the inflammatory features of melasma lesions as triggers for this disorder, 197 women with melasma who attended Asan Medical Center and Kangskin Clinic, Seoul, from June 2011 to October 2011 completed a questionnaire concerning triggering or aggravating factors. These cases were divided into “non‐inflammatory” and “inflammatory” groups. Skin biopsies and immunostaining for CD68, CD117, and leukocyte common antigen (LCA) were performed in the lesional and peri‐lesional skin of ten cases in the non‐inflammatory group and nine cases in the inflammatory group. Among the 197 subjects (mean age, 41.5 years; mean age of melasma onset, 33.8 years), 50 patients (25.4%) were categorized into the inflammatory group. This group comprised cases that had inflammatory symptoms and events that triggered the melasma lesions. The lesional dermis contained more CD68⁺ melanophages, CD117⁺ mast cells, and LCA⁺ leukocytes in the inflammatory group than in the non‐inflammatory group. Inflammatory clinical features and an increased number of inflammatory cells in the lesion may be involved in the development of melasma in Asian skin.     

急性非心源性缺血性脑卒中的病因分型与Essen卒中风险评分

目的Essen卒中风险评估（ESRS）体系可准确评估非心源性缺血性脑卒中（IS）复发的风险。而TOAST（Trial of Org 10172 in acute stroke treatment）分型则是目前应用最广泛的病因分型。本研究着眼于传统与改良的TOAST分型与ESRS的关系，从而间接了解非心源性IS的病因分型与复发风险的关系。方法①对连续纳入的非心源性IS患者行ESRS评估，将其分为低风险组（ESRS〈3分）和高风险组（ESRS≥3分）；②改良TOAST分型：动脉粥样硬化血栓形成（AT），小动脉病变（SAD），其他原因所致的缺血性脑卒中（SOD）及不明原因的缺血性脑卒中（SUD）。比较不同ESRS分值组之间TOAST分型的构成。结果纳入的316例非心源性IS患者中低风险组93例（29．4％），高风险组223例（70．6％），动脉粥样硬化性脑梗死患（以下简称AT）161例（50．9％），SAD68例（21．5％），SOD22例（7％），SUD65（20．6％）。不同ESRS分值组中不同病因分型的构成存在一定差异（P〈0．0001）。低风险组中AT较少（18／93VS161／316，P〈0．0001），SOD较多（18／93 vs 22／316，P=0．003），而高风险组中SOD相对少（4／225 vs 22／316，P=0．012）。高风险组中大动脉粥样硬化的比例并无明显高于低风险组的趋势（P〉0．05），小血管病变的比例也不明显低于低风险组（P〉0．05）。结论本研究提示①ESRS分值愈大则出现罕见病因IS的概率可能愈小，而尚不可认为出现动脉粥样硬化性IS的几率就愈大；②ESRS评分系统所包含的危险因素对于大小血管病变的影响可能是等同。     

Evolutionary trajectories of two distinct avian influenza epidemics: Parallelisms and divergences

Influenza A virus can quickly acquire genetic mutations that may be associated with increased virulence, host switching or antigenic changes. To provide new insights into the evolutionary dynamics and the adaptive strategies of distinct avian influenza lineages in response to environmental and host factors, we compared two distinct avian influenza epidemics caused by the H7N1 and H7N3 subtypes that circulated under similar epidemiological conditions, including the same domestic species reared in the same densely populated poultry area for similar periods of time.The two strains appear to have experienced largely divergent evolution: the H7N1 viruses evolved into a highly pathogenic form, while the H7N3 did not. However, a more detailed molecular and evolutionary analysis revealed several common features: (i) the independent acquisition of 32 identical mutations throughout the entire genome; (ii) the evolution and persistence of two sole genetic groups with similar genetic characteristics; (iii) a comparable pattern of amino acid variability of the HA proteins during the low pathogenic epidemics; and (iv) similar rates of nucleotide substitutions. These findings suggest that the evolutionary trajectories of viruses with the same virulence level circulating in analogous epidemiological conditions may be similar. In addition, our deep sequencing analysis of 15 samples revealed that 17 of the 32 parallel mutations were already present at the beginning of the two epidemics, suggesting that fixation of these mutations may occur with different mechanisms, which may depend on the fitness gain provided by each mutation. This highlighted the difficulties in predicting the acquisition of mutations that can be correlated to viral adaptation to specific epidemiological conditions or to changes in virus virulence.     

Review of Budd-Chiari Syndrome

This study aims to report the Budd-Chiari syndrome clinical research status and progress that has occurred in over nearly 30 years in China, and emphasize the value of imaging in facilitating the diagnosis of Budd-Chiari syndrome based on more than 2500 cases. Findings on ultrasonography, computed tomography, magnetic resonance imaging, and digital subtraction angiography images are used to propose new Budd-Chiari syndrome types and subtypes. The new subtype classification presented here has important value for guiding interventional treatment. This study also proposes a new concept of anatomical and functional obstruction of hepatic vein that stresses the compensatory value of accessory hepatic vein and azygos vein and describes the risk of manipulation of the communication branch of inferior vena cava obstruction in interventional therapy.     

Expression of hepatitis B surface antigen subtypes in liver of patients with hepatocellular carcinoma; comparison of subtypes in serum and liver

ABSTRACT— To clarify the discrepancy in hepatitis B surface antigen (HBsAg) subtypes present in the serum and liver, as well as among hepatocytes, liver specimens which were resected from 37 HBsAg-positive patients with hepatocellular carcinoma (HCC) were examined. We evaluated HBsAg and the subtypic determinants of HBsAg and hepatitis B core antigen (HBcAg) using the peroxidase-antiperoxidase (PAP) staining method. Hepatitis B antigens were more frequently detected in small tumors (HBsAg in 67%, HBcAg in 40%) than in large ones (HBsAg in 36%, HBcAg in 14%). The prevalence of each subtypic determinant in the HBsAg positive non-tumorous vs. tumorous areas was 100% vs. 67% in a, 100% vs. 57% in d, 100% vs. not tested in y, 100% vs. 53% in r and 25% vs. 0% in w (a, d, y, r and w represent subtypic determinants). There was virtually no difference in a set of subtypic determinants between the serum and liver. However, there were some variations in a set of subtypic determinants among the hepatocytes. On the other hand, liver tissue of compound subtype adyr in serum contained both cells with a,d,r and with a,y,r as well as a few cells with a,d,y,r. These findings suggest that HBV genomes in hepatocytes of type B chronic liver disease may differ genetically among cells even in the same liver tissue.     

Sustained Viral Response Is Rarely Achieved in Patients with High Viral Load of HCV RNA by Excessive Interferon Therapy

Adequate dosing of interferon (IFN) and its cost-effectiveness for sustained virological response were evaluated in relation to viral load and subtype. Prospective analysis of IFN therapy on 326 patients with chronic hepatitis C free from cirrhosis was performed using 9 or 6 million unit (MU) of IFN for six months daily and/or three times a week. Sustained virological response was achieved in 50–94% of patients with 2 × 10⁴ copies/ml (competitive RT-PCR) or <100 × 10³ copies/ml (Amplicor monitor) of HCV RNA by 468–1206 MU of IFN, but response was only 0–25% of the patients with 2 × 10^5.5 copies/ml (competitive RT-PCR) or >200 × 10³ copies/ml (Amplicor monitor), even with 468–1206 MU of IFN. A high sustained rate was demonstrated in patients with 100–200 × 10³ copies/ml of HCV RNA by 901–1206 MU of IFN, in comparison to that with 900 MU of IFN. Multivariate analysis showed that IFN dose had a significant value for the efficacy of IFN therapy in patients presenting 100–200 × 10³ copies/ml of HCV RNA. Cost efficacy analysis indicated that it cost approximately $10,000, $26,000, and $50,000–227,000 for one person-viral eradication in the patients with <100, 100–200, and >200 × 10³ copies/ml, respectively. High-dose IFN is only cost effective in patients with intermediate viral loads, and IFN therapy could be recommended in patients with <200 × 10³ copies/ml of HCV RNA.