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991.
Antony Cougnoux Miyad Movassaghi Jaqueline A. Picache James R. Iben Fatemeh Navid Alexander Salman Kyle Martin Nicole Y. Farhat Celine Cluzeau Wei-Chia Tseng Kathryn Burkert Caitlin Sojka Christopher A. Wassif Niamh X. Cawley Richard Bonnet Forbes D. Porter 《Digestive diseases and sciences》2018,63(4):870-880
Background
Niemann–Pick disease, type C (NPC) is a rare lysosomal storage disorder characterized by progressive neurodegeneration, splenomegaly, hepatomegaly, and early death. NPC is caused by mutations in either the NPC1 or NPC2 gene. Impaired NPC function leads to defective intracellular transport of unesterified cholesterol and its accumulation in late endosomes and lysosomes. A high frequency of Crohn disease has been reported in NPC1 patients, suggesting that gastrointestinal tract pathology may become a more prominent clinical issue if effective therapies are developed to slow the neurodegeneration. The Npc1 nih mouse model on a BALB/c background replicates the hepatic and neurological disease observed in NPC1 patients. Thus, we sought to characterize the gastrointestinal tract pathology in this model to determine whether it can serve as a model of Crohn disease in NPC1.Methods
We analyzed the gastrointestinal tract and isolated macrophages of BALB/cJ cNctr-Npc1m1N/J (Npc1?/?) mouse model to determine whether there was any Crohn-like pathology or inflammatory cell activation. We also evaluated temporal changes in the microbiota by 16S rRNA sequencing of fecal samples to determine whether there were changes consistent with Crohn disease.Results
Relative to controls, Npc1 mutant mice demonstrate increased inflammation and crypt abscesses in the gastrointestinal tract; however, the observed pathological changes are significantly less than those observed in other Crohn disease mouse models. Analysis of Npc1 mutant macrophages demonstrated an increased response to lipopolysaccharides and delayed bactericidal activity; both of which are pathological features of Crohn disease. Analysis of the bacterial microbiota does not mimic what is reported in Crohn disease in either human or mouse models. We did observe significant increases in cyanobacteria and epsilon-proteobacteria. The increase in epsilon-proteobacteria may be related to altered cholesterol homeostasis since cholesterol is known to promote growth of this bacterial subgroup.Conclusions
Macrophage dysfunction in the BALB/c Npc1?/? mouse is similar to that observed in other Crohn disease models. However, neither the degree of pathology nor the microbiota changes are typical of Crohn disease. Thus, this mouse model is not a good model system for Crohn disease pathology reported in NPC1 patients.992.
Thomas N. Denny Laura Andrews Mattia Bonsignori Kyle Cavanaugh Michael B. Datto Anastasia Deckard C. Todd DeMarco Nicole DeNaeyer Carol A. Epling Thaddeus Gurley Steven B. Haase Chloe Hallberg John Harer Charles L. Kneifel Mark J. Lee Raul Louzao M. Anthony Moody Zack Moore Christopher R. Polage Jamie Puglin P. Hunter Spotts John A. Vaughn Cameron R. Wolfe 《MMWR. Morbidity and mortality weekly report》2020,69(46):1743
993.
Bryan Perkins Kyle R. Gronbeck Ruixian Alexander Yue Marc A. Tompkins 《Knee surgery, sports traumatology, arthroscopy》2018,26(8):2245-2250
Purpose and hypothesis
Post-operative weight bearing after meniscal repair is a point of debate among physicians. This study sought to evaluate whether patients adhering to an immediate WBAT rehabilitation programme have a higher failure rate compared to those adhering to a more traditional, protected, NWB status following meniscal repair. The null hypothesis was that there would be no difference in failure between the two groups.Methods
A retrospective review of meniscal repair patients greater than 5 years from surgery was performed for patients receiving meniscal repair treatment. Patients were categorized by post-surgical weight-bearing status, either NWB or WBAT, and then analysed for failure of repair. Failure was defined as re-operation on the torn meniscus. The study controlled for variables including age at surgery, sex, height, weight, and BMI, classification of tear type, acuity of the tear, repair location (medial or lateral), repair location within the meniscus, repair technique, and concomitant procedures.Results
Re-operations were performed in 61 of 157 patients [38.9%]. There was no difference between weight-bearing groups for failure of meniscus repair (n.s.). The tears were acute vertical tears located in the posterior horn and body. For the 61 patients with re-operation, the average time to re-operation was 2.2 years with 10 [16%] > 5 years from surgery, 17 [28%] 2–5 years from surgery, and 34 [56%] < 2 years from surgery. In isolated meniscal repair patients (n = 62), there was no difference between weight-bearing groups for rate of re-operation (n.s.).Conclusion
Weight bearing as tolerated after meniscal repair for peripheral, vertical tears does not result in a higher failure rate than traditional, non-weight bearing over a five-year follow-up period. The clinical relevance is that, based on these data, it may be appropriate to allow weight bearing as tolerated following meniscal repair of peripheral, vertical tears.Level of evidence
Retrospective cohort study, Level III.994.
995.
Giles W Robinson Vasilisa A Rudneva Ivo Buchhalter Catherine A Billups Sebastian M Waszak Kyle S Smith Daniel C Bowers Anne Bendel Paul G Fisher Sonia Partap John R Crawford Tim Hassall Daniel J Indelicato Frederick Boop Paul Klimo Noah D Sabin Zoltan Patay Thomas E Merchant Paul A Northcott 《The lancet oncology》2018,19(6):768-784
996.
997.
Linda M. Youngwirth Kyle Freischlag Daniel P. Nussbaum Ehsan Benrashid Dan G. Blazer 《Surgical oncology》2018,27(4):676-680
Introduction
Primary sarcomas of the pancreas are rare, and the limited data regarding their presentation, oncologic profile, and survival have been derived from small case series.Methods
The National Cancer Data Base (1998–2012) was queried for patients with primary sarcomas of the pancreas. Demographic and clinical features at the time of diagnosis were evaluated for all patients. Subjects who underwent surgical resection were identified, and logistic regression was used to identify variables associated with resection. A Cox proportional hazards model was developed to identify factors associated with survival.Results
In total, 253 patients were identified. The mean age at diagnosis was 63 years, with tumors occurring more frequently in women (57.3%) and those of white race (79.8%). Tumors in the head of the pancreas were most common (63.3%). The mean size was 7.5?cm. Only 100 patients (39.5%) underwent resection, with younger age (OR?=?0.763, p?=?0.04) and smaller tumor size (OR?=?0.978, p?<?0.01) associated with resection. Chemotherapy and radiation therapy use were similar in patients who underwent resection and those who did not. Patients who underwent resection had a median survival of 17 months, compared to 6 months for patients who were not resected (p?<?0.01). Following adjustment, only older age (HR 1.257, p?=?0.03) and higher tumor grade (HR 1.997, p?=?0.01) were associated with an increased risk of death in resected patients.Conclusions
Primary pancreatic sarcomas are rare and the majority of patients do not undergo resection; thus, little is known about their oncologic profile or outcomes following pancreatectomy. Patients who undergo resection have markedly improved survival; older age and higher tumor grade are associated with decreased survival. 相似文献998.
Long-term preservation of antigenicity on tissue microarrays 总被引:8,自引:0,他引:8
DiVito KA Charette LA Rimm DL Camp RL 《Laboratory investigation; a journal of technical methods and pathology》2004,84(8):1071-1078
Tissue microarrays have facilitated the evaluation of large cohort studies; however, there is little data on the best method for preserving sections once they are cut. We assessed three methods of storing precut breast cancer microarray slides: paraffin coating and storage in a nitrogen desiccator, either alone or in combination. We tested the durability of three antigens, cytokeratin, estrogen receptor, and Ki-67 on microarrays stored under these conditions for 3 months at room temperature. Staining was assessed with both manual scoring using traditional brown stain (0-3+) as well as automated scoring using fluorescently stained sections. Staining intensity was compared to that obtained from freshly cut slides. Slides stored under ambient conditions (room temperature and air) for 3 months exhibited marked degradation of all target antigens, in some cases resulting in slides that were virtually unreadable. We found that combined paraffin coating and nitrogen storage resulted in the best preservation of antigenicity, with retention of 72-99% of the antigenicity of a freshly cut slide, depending upon the marker and detection system used. The use of either paraffin coating or nitrogen storage alone protected slides to a lesser degree. 相似文献
999.
Jaiswal VR Baird J Fleming J Miller DS Sharma S Molberg K 《Archives of pathology & laboratory medicine》2003,127(7):879-882
Lymphangioleiomyomatosis (lymphangiomyomatosis [LAM]), a rare disease of unknown etiology that is seen only in women usually in the reproductive period, generally presents with features of pulmonary involvement. Extrapulmonary involvement, such as angiomyolipomas and retroperitoneal adenopathy, can occur in up to 75% of cases. It is very rare, however, for patients to present with features of extrapulmonary LAM. We present an unusual, localized case of LAM presenting with neurologic symptoms related to a retroperitoneal mass in a 51-year-old woman. Magnetic resonance imaging showed that the mass involved retroperitoneal lymph nodes, and a clinical diagnosis of atypical sarcoma (possibly from a uterine primary) was made. The mass was resected, and a total abdominal hysterectomy was performed. On pathologic examination, the mass showed classic histologic features of LAM with spread along lymphatic channels in the lymph nodes. Intralymphatic projections simulated lymphatic metastasis; however, the cytologic features were benign. Immunostains revealed the tumor to be positive for smooth muscle actin and desmin, but negative for HMB-45. The uterus was unremarkable, except for a subserosal leiomyoma. Although intratumoral variability for HMB-45 has recently been described, to the best of our knowledge, this is the first documented case of HMB-45-negative, histologically classic LAM. Because of the presence of several atypical features in this case, such as age, location, compressive neurologic presentation, radiologic impression of atypical sarcoma, and HMB-45 negativity, we feel that this case may represent a distinct, as yet uncharacterized variant of LAM. 相似文献
1000.