Differences in Clinical Manifestations and Tumor Features Between Metastatic Pheochromocytoma/Paraganglioma Patients With and Without Germline SDHB Mutation

ObjectiveTo compare metastatic pheochromocytoma/paraganglioma (MPP) patients with germline SDHB mutations (SDHB MPP) and without SDHB mutations (non-SDHB MPP) in terms of baseline clinical manifestations, tumor characteristics, and outcomes.MethodsClinical data were retrospectively reviewed in 101 MPP patients, including 34 SDHB MPP patients and 61 non-SDHB MPP patients.ResultsSDHB MPP patients presented at a younger age at onset, diagnosis, or metastasis (25 ± 16 vs 36 ± 14, 28 ± 17 vs 38 ± 15, and 31 ± 17 vs 44 ± 14 years old, respectively, P < .01 for all) than non-SDHB patients. Compared with their non-SDHB counterparts, SDHB patients were more likely to have paragangliomas (83% vs 47%, P < .05), synchronous metastases (44% vs 23%, P < .05), bone metastases (80% vs 48%, P < .01), and a shorter progression-free survival (3 years vs 5 years, P < .01). The Ki-67 index was higher in SDHB tumors (P < .05). The 5- and 10-year survival rates were 79% and 74%, respectively, in all patients. Seventeen patients died from MPP, and the time from metastasis to death in patients who had received systemic therapy was significantly longer than in those who had not (3.1 ± 1.5 vs 1.4 ± 0.7 years, P < .01).ConclusionCompared with MPP patients without SDHB mutations, MPP patients with SDHB mutations were younger at onset, diagnosis, or metastasis; had a higher incidence of synchronous metastases, higher ratio of paraganglioma, and higher Ki-67 index; had a shorter postoperative progression-free survival; and were more likely to develop bone metastasis or sole liver metastasis. Our results suggest that patients with SDHB mutations should be identified early and monitored regularly to achieve optimal clinical outcomes.     

Pathologic Features Associated With Molecular Subtypes of Well-Differentiated Thyroid Cancer

ObjectiveTo determine the association between pathologic features and molecular classes (BRAF-like, RAS-like, and non-BRAF-like non-RAS-like [NBNR]).MethodsRetrospective review of a merged database containing 676 patients, 84% (571/676) were assigned to a molecular class from publicly accessible sequenced data of thyroid neoplasms.ResultsThe merged cohort included 571 neoplasms: 353 (62%) BRAF-like, 172 (30%) RAS-like, and 46 (8.1%) NBNR. Lymph node metastasis (any N1 disease) was present in 166/337 (49%) of BRAF-like, 23/164 (14%) of RAS-like, and 0/46 (0%) of NBNR and are significantly different (P < .001). Gross extra-thyroidal extension was observed in 27 patients, including 24/331 (7%) of BRAF-like, 2/160 (1%) of RAS-like, and 1/46 (2%) of NBNR (P = .01). N1B lymph node metastases or T4 disease was present in 74/333 (22%) of BRAF-like, 10/160 (6%) of RAS-like, and 1/46 (2%) of NBNR (P < .0001). Distant metastasis was present in 4/151 (2.6%) of BRAF-like, 2/50 (4%) of RAS-like and 0/46 for NBNR (P = .627). Angioinvasion was present in 0/81 (0%) of BRAF-like, 3/53 (6%) of RAS-like, and 3/46 (7%) of NBNR (P = .08); and multifocality was present in 27/81 (33%) of BRAF-like, 9/53 (17%) of RAS-like, and 1/46 (2%) for NBNR (P = .0001).ConclusionPathological features of metastasis, gross extra-thyroidal extension, and multifocality were more prevalent in BRAF-like samples compared to RAS-like and NBNR. A trend towards increased frequency of angioinvasion in RAS-like and NBNR cancers compared to BRAF-like samples was observed. Further studies are needed to evaluate if preoperative knowledge of molecular mutations in thyroid tumors aids in decision-making regarding extent of surgery.     

Novel Giant Siphovirus from Bacillus anthracis Features Unusual Genome Characteristics

Here we present vB_BanS-Tsamsa, a novel temperate phage isolated from Bacillus anthracis, the agent responsible for anthrax infections in wildlife, livestock and humans. Tsamsa phage is a giant siphovirus (order Caudovirales), featuring a long, flexible and non-contractile tail of 440 nm (not including baseplate structure) and an isometric head of 82 nm in diameter. We induced Tsamsa phage in samples from two different carcass sites in Etosha National Park, Namibia. The Tsamsa phage genome is the largest sequenced Bacillus siphovirus, containing 168,876 bp and 272 ORFs. The genome features an integrase/recombinase enzyme, indicative of a temperate lifestyle. Among bacterial strains tested, the phage infected only certain members of the Bacillus cereus sensu lato group (B. anthracis, B. cereus and B. thuringiensis) and exhibited moderate specificity for B. anthracis. Tsamsa lysed seven out of 25 B. cereus strains, two out of five B. thuringiensis strains and six out of seven B. anthracis strains tested. It did not lyse B. anthracis PAK-1, an atypical strain that is also resistant to both gamma phage and cherry phage. The Tsamsa endolysin features a broader lytic spectrum than the phage host range, indicating possible use of the enzyme in Bacillus biocontrol.     

Impact of Pancreatic Neuroendocrine Tumor on Mortality in Patients With von Hippel-Lindau Disease

ObjectiveThe main causes for morbidity and mortality in von Hippel-Lindau (VHL) disease are central nervous system hemangioblastoma and clear cell renal cell carcinoma, but the effect of VHL-related pancreatic neuroendocrine tumors (PNET) on patient outcome is unclear. We assessed the impact of PNET diagnosis in patients with VHL on all-cause mortality (ACM) risk.MethodsWe used the Surveillance, Epidemiology, and End Results database. Of 16 344 patients, 170 had VHL based on clinical diagnostic criteria, and 510 patients had PNET (91 VHL-related and 419 sporadic).ResultsSurvival analysis demonstrated a lower ACM among patients with VHL-related PNET compared to patients with sporadic PNET (log-rank test, P = .011). Among patients with VHL, ACM risk was higher with vs without PNET (P = .029). The subgroup analysis revealed a higher ACM risk with metastatic PNET (sporadic P = .0031 and VHL-related P = .08) and a similar trend for PNET diameter ≥3 cm (P = .06 and P = 0.1 in sporadic and VHL-related PNET, respectively). In a multivariable analysis of patients with VHL, diagnosis with PNET by itself was associated with a trend of lower risk for ACM, while presence of metastatic PNET was independently associated with increased ACM risk.ConclusionDiagnosis with PNET is not associated with a higher ACM risk in VHL by itself. The independent association of advanced PNET stage with higher mortality risk emphasizes the importance of active surveillance for detecting high-risk PNET at an early stage to allow timely intervention.     

Clinical and Pathologic Features of a Suspected Selenium Deficiency in Captive Plains Zebras

Previous studies have shown that selenium (Se) deficiency is associated with nutritional myopathy, known as white muscle disease (WMD), in horses. However, correlations between Se deficiency and clinical findings, such as hematologic biochemical values and pathological features, have not been evaluated in captive plains zebras. The purpose of the present study was to investigate the clinical and pathologic features that may be caused by a Se deficiency in the captive plains zebra. Clinical findings, feed analyses, hematologic biochemical analyses, response to treatment, and pathologic examination were assessed in six affected plains zebras. The dietary concentration of Se in feed was also tested. Sudden death occurred in two cases during the first day of the onset of symptoms. Two zebras died at 4 days and two zebras survived after treatment. The clinical signs in affected animals were characterized by general weakness, astasia, and abnormal postural positions. The Se concentration in hay from the breeding stable was low, based on the reference value. Glutathione peroxidase (GSH-Px) activity was lower compared with the equine reference value. Multiple areas of subcutaneous steatitis and pale skeletal muscle and myocardium were revealed at gross necropsy. Degeneration and necrosis of myocardial and skeletal muscles, as well as congestion of the liver, lung, and kidney were found via histopathological examination. No suspected bacterial infections were found. Feed analyses, response to treatment, serum GSH-Px activity, and pathological features suggest that Se deficiency may have caused the disease in the six affected captive plains zebra.     

Comparison of Clinical Features and Prognostic Factors of Cryptococcal Meningitis Caused by Cryptococcus neoformans in Patients With and Without Pulmonary Nodules

Mycopathologia - Whether the clinical features of cryptococcal meningitis (CM) patients vary with the coexistence of pulmonary nodules is not clear. This study aimed to compare the clinical...     

The Clinical Profiles of Individuals With and Without Root Surface Caries1

As part of a collaborative multidisciplinary investigation of root surface caries (RSC), 273 subjects (median age = 57) were clinically evaluated for coronal caries, debris, calculus, gingivitis, periodontal pocketing, recession, abrasion, as well as RSC. The entire study group was divided into three subgroups: (1) subjects whose exposed root surface were without lesions or restorations (non-diseased individuals, n= 43); (2) subjects whose exposed root surfaces had one or more lesions and may or may not have had restorations (diseased individuals, n= 110); (3) subjects with one or more restorations but no lesions, since it was not known whether these restorations were preceded by RSC or abrasion the disease status of these individuals was unclear (n= 120). A comparison of Subgroup 1 (unequivocally non-diseased) and Subgroup 2 (unequivocally diseased) revealed that subjects without RSC had more teeth, less coronal caries, less recession, less debris, less calculus, less gingivitis, and more abrasion. We infer that the common factor underlying most if not all of the subgroup differences is oral hygiene which must therefore be a major disease determinant.     

Molecular-Genetic Features of Pancreatic Neuroendocrine Tumors

Russian Journal of Genetics - Neuroendocrine tumors (NETs) account for less than 3% of primary neoplasias of the pancreas. Despite success of the classification, the discovery of new methods of...     

Comparative Characteristics of Immunological,Clinical and Morphological Features of Human Lymphoid Tumors in Respect with Tumor Genesis and Progression

We describe three lymphoid tumors with the same immunophenotype characteristic for chronic lymphoid leukemia (CD19⁺/CD5⁺, clonality of the light immunoglobulin chains, CD23⁺ and CD10^–). However, clinical picture and morphology of neoplastic cells dictate different clinical forms of these cases: chronic lymphoid leukemia, large cell transformation of chronic lymphoid leukemia and diffuse large B-cell lymphoma. Taking into account that immunophenotype reflects the origin of tumor, while clinical outcome and morphological features of cells reflect the stage of tumor progression and/or pathway of tumor formation, we discuss the approach to natural classification of lymphoid tumors based on the process of their evolution.     

局部刮除肿瘤联合放疗治疗骨巨细胞瘤的临床研究

目的：探讨局部刮除肿瘤联合术中适形固定施源器模型插植放疗和术后外照射治疗骨巨细胞瘤（GCTB）的临床疗效和毒副反应。方法：将2006年2月．2008年2月在湖南省肿瘤医院初次治疗的长骨GCTB患者30例随机分为单纯局部刮除手术组和局部刮除手术联合放疗组,两组患者均行局部肿瘤刮除术,局部刮除手术联合放疗组在此基础上给予术中适形固定施源器模型插植放疗和术后外照射,治疗后比较两组的临床疗效和毒副反应。结果：局部刮除手术联合放疗组1、3、5年均未复发,而单纯局部刮除手术组的1、3、5年复发率分别为9．1％、27．3％、45．5％,3年和5年复发率均显著高于局部刮除手术联合放疗组（P〈0．05）。局部刮除手术联合放疗组中未见严重相关性毒性和死亡,术后两组的关节功能评分比较无明显差剐（P〉0．05）。结论：局部手术刮除病灶结合术中和术后放疗治疗骨巨细胞瘤可显著降低患者的复发率,且不影响关节功能,是一种较为安全的治疗方法。     

Ultrastructural Characteristics of Adult Rat Adrenocortical Cells Maintained in vitro With and Without ACTH

Bhattacharyya, T. K., Butler, D. G., Price, C. S. 1980. Ultrastructural characteristics of adult rat adrenocortical cells maintained in vitro with and without ACTH. (Ramsay Wright Zoological Laboratories, Department of Zoology, University of Toronto, and Division of Endocrinology, Toronto Western Hospital, and Department of Medicine, University of Toronto, Canada.) — Acta zool. (Stockh.) 61(1): 9–21. The ultrastructural morphology of adrenocortical cells of adult rats maintained in culture for four days with and without corticotropin (ACTH) was studied in comparison to freshly dissociated cells. Identification of cells belonging to zona glomerulosa, zona fasciculata, and zona reticularis was made on the characteristics of the mitochondria and smooth endoplasmic reticulum (SER), and was confirmed by comparison with cellular layers from intact adrenals. Without ACTH, glomerulosa and fasciculata cells showed disappearance of SER, atrophied Golgi apparatus (GA), and a striking proliferation of granular reticulum. Fascicular cells had a loss in mitochondrial matrix density and the mitochondrial cristae showed a tendency to convert to lamellar glomerulosa-type cristae. Zona reticularis cells were not strikingly altered. Maintenance with ACTH led to increased cell size and islet formation of cortical cells. Glomerulosa cells had normal appearance and fasciculata cells manifested a pronounced development of GA and SER, and a normal configuration of mitochondria. The effects of ACTH on glomerulosa cells suggest a trophic influence of ACTH on these cells in vitro. The alterations observed in fascicular cell mitochondria and SER can be explained in terms of known concepts of steroid biosynthesis and basically agree with the patterns of steroid synthesis observed in these cells previously (Price et al. 1975).     

Clinical and Pathologic Features of Cynomolgus Macaques (Macaca fascicularis) Infected with Aerosolized Yersinia pestis

Since the anthrax attacks of 2001, the emphasis on developing animal models of aerosolized select agent pathogens has increased. Many scientists believe that nonhuman primate models are the most appropriate to evaluate pulmonary response to, vaccines for, and treatments for select agents such as Yersinia pestis (Y. pestis), the causative agent of plague. A recent symposium concluded that the cynomolgus macaque (Macaca fascicularis) plague model should be characterized more fully. To date, a well-characterized cynomolgus macaque model of pneumonic plague using reproducible bioaerosols of viable Y. pestis has not been published. In the current study, methods for creating reproducible bioaerosols of viable Y. pestis strain CO92 (YpCO92) and pneumonic plague models were evaluated in 22 Indonesian-origin cynomolgus macaques. Five macaques exposed to doses lower than 250 CFU remained free of any indication of plague infection. Fifteen macaques developed fever, lethargy, and anorexia indicative of clinical plague. The 2 remaining macaques died without overt clinical signs but were plague-positive on culture and demonstrated pathology consistent with plague. The lethal dose of plague in humans is reputedly less than 100 organisms; in this study, 66 CFU was the dose at which half of the macaques developed fever and clinical signs (ED₅₀), The Indonesian cynomolgus macaque reproduces many aspects of human pneumonic plague and likely will provide an excellent model for studies that require a macaque model.Yersinia pestis is the causative agent of plague. Likely more people worldwide have died from Y. pestis infections than from any other single infectious disease.^26,27 Bubonic plague, the most common form of the disease, results when the bacterium is inoculated into the skin, typically by means of flea bites. The resulting cutaneous infection spreads to local lymph nodes; the swollen lymph nodes are known as bubos and often serve as a source of systemic infection. Although less common, the bacterium also can spread by aerosol, causing pneumonic plague. Pneumonic plague can result from pulmonary spread of systemic infection or from deliberate dissemination and is associated with nearly 100% human mortality if left untreated. Y. pestis is susceptible to commonly available antibiotics if treatment begins soon after infection. However, depending on the route of infection, the time at which infection is confirmed is often too late for antibiotics to prevent significant morbidity or mortality.¹⁰ Because pneumonic plague is the form most likely to be seen in bioterrorism events,¹⁶ interest in animal models has arisen to support development of vaccines and improved therapeutics.Potential vaccines and therapeutic agents for plague must protect against the pneumonic disease, but contemporary published data regarding disease pathogenesis using aerosolized Y. pestis pathogenesis in nonhuman primates are scant.^4,9,21,23,24 In the United States, when vaccine or antibiotic efficacy cannot be evaluated in humans, an animal species that is reasonably expected to recapitulate human disease must be used.⁹ For many biothreat agents such as plague, a nonhuman primate model often is required. Although some laboratories have examined the cynomolgus macaque model of aerosolized plague briefly,¹ no published reports fully characterize this model. Published studies have examined plague in the African green monkey or vervet (Chlorocebus spp., formerly Cercopithecus aethiops) and rhesus macaque (Macaca mulatta).¹ Vervets reportedly are more sensitive to plague than are macaques,^4,24 such that some vervets are susceptible to infection with vaccine strains, casting some doubt on applicability of this species for plague studies.¹ The disease in rhesus macaques differs from that in humans in that rhesus macaques frequently develop disseminated intravascular coagulation (DIC) and chronic pneumonia as a result of pneumonic plague while humans usually develop acute pneumonia without DIC.^1,7Many participants at a recent symposium sponsored by the Food and Drug Administration and National Institute of Allergy and Infectious Disease endorsed the development of a cynomolgus macaque pneumonic plague model to support plague therapeutic and vaccine studies.⁸ The current study was undertaken to evaluate the Indonesian cynomolgus macaque as a model of aerosolized Y. pestis Colorado 92 (YpCO92) for subsequent vaccine and therapeutic trials. We also sought to determine whether fever development could be used to determine a humane endpoint to the study, as an alternative to LD₅₀ methods.     

帕金森病单纯淡漠的临床特征及发生机制

帕金森病(Parkinson disease,PD)是常见的神经变性疾病,除静止性震颤、运动迟缓、肌强直、步态和姿势障碍等运动症状外,近年研究发现其还存在神经精神、睡眠、感觉及自主神经障碍等多种非运动症状。PD单纯淡漠是不伴痴呆和抑郁的淡漠,其与运动症状及多种非运动症状相关,严重影响患者的日常生活能力及生活质量。PD单纯淡漠的发生涉及神经解剖、神经病理、神经生化及神经免疫炎症等机制。本文将对PD单纯淡漠的临床特征及发生机制进行阐述。     

33例普通型新型冠状病毒肺炎的临床特征分析

摘要 目的：总结33例普通型新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)患者的临床特征,为临床治疗提供指导。方法：回顾性分析我院收治的33例COVID-19患者的临床资料,对其特征进行分析。结果：31例患者有流行病学接触史,其中16例有家庭聚集情况。最常见的临床症状为发热、咳嗽等上呼吸道感染症状,少见可出现腹泻、上腹部不适,罕见头痛、视神经脊髓炎。患者治疗后实验室大部分指标均改善明显,但淋巴细胞以及心肌损伤标记物高敏心肌肌钙蛋白T(high sensitive cardiac troponin,hs-cTnT)改善稍晚。97.0 %的患者胸部CT中以磨玻璃影为主,但这与普通病毒性肺炎无明显区别,老年患者可合并胸腔积液。结论：在西安地区收治的COVID-19患者多数有明确的流行病学史,临床表现主要为发热咳嗽,但也可累及消化系统及神经系统出现症状。患者经治疗后实验室指标大部分改善明显,肺部影像学以磨玻璃样改变居多,也可出现胸腔积液。普通型患者经治疗后预后良好。     

常见消化道黏膜下肿物的临床特点及治疗方法

目的:探讨常见消化道黏膜下肿物(submucosal tumors,SMTs)的临床特点、治疗方式及安全性。方法:选择2014年5月至2016年3月在哈医大一院经内镜切除的并经病理及免疫组化明确诊断的消化道粘膜下肿物的患者共49例。所有患者术后3个月、6个月及12个月后随诊复查胃镜。统计每种肿物的患者临床症状,各种黏膜下肿物的性别分布、大小,及在消化道的分布。计算超声内镜的诊断率,总结病理结果。结果:49例患者中,间质瘤25例,类癌9例,平滑肌瘤8例,异位胰腺4例,脂肪瘤2例,颗粒细胞瘤1例。间质瘤分布以胃底、胃体多见。类癌以直肠最多见,胃内也可见。平滑肌瘤多分布于食管,也可见于胃。异位胰腺多分布于胃窦。通过内镜黏膜下挖除术(Endoscopic submucosal excavation,ESE)切除42例,粘膜下隧道切除术(Submucosal tunneling endoscopic resection,STER)切除4例,还有3例行内镜下黏膜切除(Endoscopic Mucosal Resection,EMR)。所有患者术后均无迟发性出血、严重感染及死亡病例发生。随访3-22个月,所有患者均无复发。结论:黏膜下肿物在内镜及超声内镜各有特点。超声内镜对黏膜下肿物的诊断与治疗具有重要的指导意义。双镜联合使SMTs的内镜下各种治疗方式(EMR、ESE、STER)更有安全保障,使患者受益最大。     

中华蟾蜍蝌蚪对高渗溶液的耐受性

为了解中华蟾蜍蝌蚪对高渗溶液的耐受性,采用常规静态实验,用蔗糖调节溶液渗透压对蟾蜍蝌蚪进行渗透耐受实验;采用方差分析统计溶液渗透压对蟾蜍蝌蚪的存活率、体积变化和活动性的影响。结果显示,蟾蜍蝌蚪能够忍受溶液渗透压在一定范围内的变化,对渗透压较低的溶液其适应对策为调节,而对渗透压较高的溶液则为协变。蝌蚪对水溶液的耐受渗透压为1485．24mOsm,其存活率随渗透压增高而降低;同一渗透压下,蝌蚪存活率随在溶液中暴露时间的延长而降低。蟾蜍蝌蚪体内水分在不同浓度溶液中丧失的程度存在显著差异,即使在同一浓度的溶液中,体积会随时间的增加而不断缩小,并且溶液浓度越高,体积减小的速率越大。身体失水对蝌蚪的行为性会产生一定的影响,蝌蚪的活泼性随时间的延长而降低。