BACKGROUND There is concern regarding potential long-term cardiotoxicity with systemic distribution of metals in total joint arthroplasty(TJA)patients.AIM To determine the association of commonly used implant metals w...BACKGROUND There is concern regarding potential long-term cardiotoxicity with systemic distribution of metals in total joint arthroplasty(TJA)patients.AIM To determine the association of commonly used implant metals with echocardiographic measures in TJA patients.METHODS The study comprised 110 TJA patients who had a recent history of high chromium,cobalt or titanium concentrations.Patients underwent two-dimensional,three-dimensional,Doppler and speckle-strain transthoracic echocardiography and a blood draw to measure metal concentrations.Age and sex-adjusted linear and logistic regression models were used to examine the association of metal concentrations(exposure)with echocardiographic measures(outcome).RESULTS Higher cobalt concentrations were associated with increased left ventricular end-diastolic volume(estimate 5.09;95%CI:0.02-10.17)as well as left atrial and right ventricular dilation,particularly in men but no changes in cardiac function.Higher titanium concentrations were associated with a reduction in left ventricle global longitudinal strain(estimate 0.38;95%CI:0.70 to 0.06)and cardiac index(estimate 0.08;95%CI,-0.15 to-0.01).CONCLUSION Elevated cobalt and titanium concentrations may be associated with structural and functional cardiac changes in some patients.Longitudinal studies are warranted to better understand the systemic effects of metals in TJA patients.展开更多
BACKGROUND Coronavirus disease 2019(COVID-19)disease can frequently affect the liver.Data on hepatic histopathological findings in COVID-19 is scarce.AIM To characterize hepatic pathological findings in patients with ...BACKGROUND Coronavirus disease 2019(COVID-19)disease can frequently affect the liver.Data on hepatic histopathological findings in COVID-19 is scarce.AIM To characterize hepatic pathological findings in patients with COVID-19.METHODS We conducted a systematic review with meta-analysis registered on PROSPERO(CRD42020192813),following PRISMA guidelines.Eligible trials were those including patients of any age and COVID-19 diagnosis based on a molecular test.Histopathological reports from deceased COVID-19 patients undergoing autopsy or liver biopsy were reviewed.Articles including less than ten patients were excluded.Proportions were pooled using random-effects models.Q statistic and I2 were used to assess heterogeneity and levels of evidence,respectively.RESULTS We identified 18 studies from 7 countries;all were case reports and case series from autopsies.All the patients were over 15 years old,and 67.2%were male.We performed a meta-analysis of 5 studies,including 116 patients.Pooled prevalence estimates of liver histopathological findings were hepatic steatosis 55.1%[95%confidence interval(CI):46.2-63.8],congestion of hepatic sinuses 34.7%(95%CI:7.9-68.4),vascular thrombosis 29.4%(95%CI:0.4-87.2),fibrosis 20.5%(95%CI:0.6-57.9),Kupffer cell hyperplasia 13.5%(95%CI:0.6-54.3),portal inflammation 13.2%(95%CI:0.1-48.8),and lobular inflammation 11.6%(95%CI:0.3-35.7).We also identified the presence of venous outflow obstruction,phlebosclerosis of the portal vein,herniated portal vein,periportal abnormal vessels,hemophagocytosis,and necrosis.CONCLUSION We found a high prevalence of hepatic steatosis and vascular thrombosis as major histological liver features.Other frequent findings included portal and lobular inflammation and Kupffer cell hyperplasia or proliferation.Further studies are needed to establish the mechanisms and implications of these findings.展开更多
AIM: To investigate whether accelerated catabolism of ganglioside and decreased ganglioside content contribute to the etiology of pro-inflammatory intestinal disease. METHODS: Intestinal mucosa from terminal ileum or ...AIM: To investigate whether accelerated catabolism of ganglioside and decreased ganglioside content contribute to the etiology of pro-inflammatory intestinal disease. METHODS: Intestinal mucosa from terminal ileum or colon was obtained from patients with ulcerative colitis or inflammatory Crohn's disease(n = 11) undergoing bowel resection and compared to control samples of normal intestine from patients with benign colon polyps(n = 6) and colorectal cancer(n = 12) in this observational case-control study. Gangliosides and phospholipids of intestinal mucosa were characterized by class and ceramide or fatty acid composition using liquid chromatography triple-quad mass spectrometry. Content and composition of ganglioside classes GM1, GM3, GD3, GD1 a, GT1 and GT3 were compared among subject groups. Content and composition of phospholipid classes phosphatidylcholine(PC) and phosphatidylethanolamine were compared among subject groups. Unsaturation index of individual ganglioside and phospholipid classes was computed and compared among subject groups. Ganglioside catabolism enzymes beta-hexosaminidase A(HEXA) and sialidase-3(NEU3) were measured in intestinal mucosa using western blot and compared among subject groups. RESULTS: Relative GM3 ganglioside content was 2-fold higher(P < 0.05) in intestine from patients with inflammatory bowel disease(IBD) compared to control intestine. The quantity of GM3 and ratio of GM3/GD3 was also higher in IBD intestine than control tissue(P < 0.05). Control intestine exhibited 3-fold higher(P < 0.01) relative GD1 a ganglioside content than IBD intestine. GD3 and GD1 a species of ganglioside containing three unsaturated bonds were present in control intestine, but were not detected in IBD intestine. The relative content of PC containing more than two unsaturated bonds was 30% lower in IBD intestine than control intestine(P < 0.05). The relative content of HEXA in IBD intestine was increased 1.7-fold(P < 0.05) and NEU3 was increased 8.3-fold(P < 0.01) compared to normal intestine. Intestinal mucosa in IBD is characterized by increased GM3 content, decreased GD1 a, and a reduction in polyunsaturated fatty acid constituents in GD3, GD1 a and PC.CONCLUSION: This study suggests a new paradigm by proposing that IBD occurs as a consequence of increased metabolism of specific gangliosides.展开更多
Diffuse idiopathic skeletal hyperostosis(DISH) is a prevalent noninflammatory spondyloarthropathy characterized by ectopic mineral formation along the anterolateral aspect of the vertebral column, yet little is known ...Diffuse idiopathic skeletal hyperostosis(DISH) is a prevalent noninflammatory spondyloarthropathy characterized by ectopic mineral formation along the anterolateral aspect of the vertebral column, yet little is known about its underlying pathogenesis. Our objective was to evaluate the histopathological features and composition of ectopic mineral within spinal tissues affected by DISH in humans. Thoracic spine segments from six embalmed cadaveric donors(one female and five males;median age 82 years)meeting the radiographic diagnostic criteria for DISH were evaluated using radiological, histological, and physical analyses. Overall,the histological features of ectopic mineralization at individual motion segments were heterogeneous, including regions of heterotopic ossification and dystrophic calcification. Heterotopic ossifications were characterized by woven and lamellar bone,multifocal areas of metaplastic cartilage, and bony bridges along the anterior aspect of the intervertebral disc space. Dystrophic calcifications were characterized by an amorphous appearance, a high content of calcium and phosphorus, an X-ray diffraction pattern matching that of hydroxyapatite, and radiodensities exceeding that of cortical bone. Dystrophic calcifications were found within the anterior longitudinal ligament and annulus fibrosus in motion segments both meeting and not meeting the radiographic criteria for DISH. In summary, our findings indicate that in DISH, ectopic mineral forms along the anterior aspect of the spine by both heterotopic ossification and dystrophic calcification of fibrocartilaginous tissues. Although both types of ectopic mineralization are captured by current radiographic criteria for DISH, dystrophic calcification may reflect a distinct disease process or an early stage in the pathogenesis of DISH.展开更多
BACKGROUND Leukocytes,such as T cells and macrophages,play an important role in tumorigenesis.CC chemokine ligand(CCL)4,which is produced by lymphocytes and macrophages,has been found to be expressed in the mucosa of ...BACKGROUND Leukocytes,such as T cells and macrophages,play an important role in tumorigenesis.CC chemokine ligand(CCL)4,which is produced by lymphocytes and macrophages,has been found to be expressed in the mucosa of the gastrointestinal tract and is a potent chemoattractant for various leukocytes.AIM To examine CCL4 expression and its genetic polymorphism rs10491121 in patients with colorectal cancer(CRC)and evaluate their prognostic significance.METHODS Luminex technology was used to determine CCL4 Levels in CRC tissue(n=98),compared with paired normal tissue,and in plasma from patients with CRC(n=103),compared with healthy controls(n=97).Included patients had undergone surgical resection for primary colorectal adenocarcinomas between 1996 and 2019 at the Department of Surgery,Ryhov County Hospital,Jönköping,Sweden.Reverse transcription quantitative PCR was used to investigate the CCL4 gene expression in CRC tissue(n=101).Paired normal tissue and TaqMan single nucleotide polymorphism assays were used for the CCL4 rs10491121 polymorphism in 610 CRC patients and 409 healthy controls.RESULTS The CCL4 protein and messenger RNA expression levels were higher in CRC tissue than in normal paired tissue(90%,P<0.001 and 45%,P<0.05,respectively).CRC tissue from patients with localized disease had 2.8-fold higher protein expression levels than that from patients with disseminated disease.Low CCL4 protein expression levels in CRC tissue were associated with a 30%lower cancer-specific survival rate in patients(P<0.01).The level of plasma CCL4 was 11%higher in CRC patients than in healthy controls(P<0.05)and was positively correlated(r=0.56,P<0.01)with the CCL4 protein level in CRC tissue.The analysis of CCL4 gene polymorphism rs10491121 showed a difference(P<0.05)between localized disease and disseminated disease in the right colon,with a dominance of allele A in localized disease.Moreover,the rate of the A allele was higher among CRC patients with mucinous cancer than among those with nonmucinous cancer.CONCLUSION The present study indicates that the CRC tissue levels of CCL4 and CCL4 gene polymorphism rs10491121,particularly in the right colon,are associated with clinical outcome in CRC patients.展开更多
AIM: To investigate a classification of endocytoscopy (ECS) images in Barrett’s esophagus (BE) and evaluate its diagnostic performance and interobserver variability.
It was hypothesized that mesenchymal stem cells(MSCs) could provide necessary trophic factors when seeded onto the surfaces of commonly used nerve graft substitutes. We aimed to determine the gene expression of MSCs w...It was hypothesized that mesenchymal stem cells(MSCs) could provide necessary trophic factors when seeded onto the surfaces of commonly used nerve graft substitutes. We aimed to determine the gene expression of MSCs when influenced by Avance■ Nerve Grafts or Neura Gen■ Nerve Guides. Human adipose-derived MSCs were cultured and dynamically seeded onto 30 Avance■ Nerve Grafts and 30 Neura Gen■ Nerve Guides for 12 hours. At six time points after seeding, quantitative polymerase chain reaction analyses were performed for five samples per group. Neurotrophic [nerve growth factor(NGF), glial cell line-derived neurotrophic factor(GDNF), pleiotrophin(PTN), growth associated protein 43(GAP43) and brain-derived neurotrophic factor(BDNF)], myelination [peripheral myelin protein 22(PMP22) and myelin protein zero(MPZ)], angiogenic [platelet endothelial cell adhesion molecule 1(PECAM1/CD31) and vascular endothelial cell growth factor alpha(VEGFA)], extracellular matrix(ECM) [collagen type alpha I(COL1A1), collagen type alpha III(COL3A1), Fibulin 1(FBLN1) and laminin subunit beta 2(LAMB2)] and cell surface marker cluster of differentiation 96(CD96) gene expression was quantified. Unseeded Avance■ Nerve Grafts and Neura Gen■ Nerve Guides were used to evaluate the baseline gene expression, and unseeded MSCs provided the baseline gene expression of MSCs. The interaction of MSCs with the Avance■ Nerve Grafts led to a short-term upregulation of neurotrophic(NGF, GDNF and BDNF), myelination(PMP22 and MPZ) and angiogenic genes(CD31 and VEGFA) and a long-term upregulation of BDNF, VEGFA and COL1A1. The interaction between MSCs and the Neura Gen■ Nerve Guide led to short term upregulation of neurotrophic(NGF, GDNF and BDNF) myelination(PMP22 and MPZ), angiogenic(CD31 and VEGFA), ECM(COL1A1) and cell surface(CD96) genes and long-term upregulation of neurotrophic(GDNF and BDNF), angiogenic(CD31 and VEGFA), ECM genes(COL1A1, COL3A1, and FBLN1) and cell surface(CD96) genes. Analysis demonstrated MSCs seeded onto Neura Gen■ Nerve Guides expressed significantly higher levels of neurotrophic(PTN), angiogenic(VEGFA) and ECM(COL3A1, FBLN1) genes in the long term period compared to MSCs seeded onto Avance■ Nerve Grafts. Overall, the interaction between human MSCs and both nerve graft substitutes resulted in a significant upregulation of the expression of numerous genes important for nerve regeneration over time. The in vitro interaction of MSCs with the Neura Gen■ Nerve Guide was more pronounced, particularly in the long term period(> 14 days after seeding). These results suggest that MSC-seeding has potential to be applied in a clinical setting, which needs to be confirmed in future in vitro and in vivo research.展开更多
Objective: To describe the demographics and outcome of patients with candidal vertebral osteomyelitis (CVO). CVO is a rare and frequently misdiagnosed condition. It may lead to destruction of the vertebral bodies, spi...Objective: To describe the demographics and outcome of patients with candidal vertebral osteomyelitis (CVO). CVO is a rare and frequently misdiagnosed condition. It may lead to destruction of the vertebral bodies, spinal cord compression and neurological deficits. Methods: The medical records of all patients diagnosed with CVO at our institution between 01/01/1990-12/31/2009 were reviewed. The cumulative probability of treatment success was assessed by the Kaplan-Meier survival method. Patients were followed until death, failure, or loss of follow-up. Results: Nine patients developed CVO during the 20 year study period. The cervical spine was involved in 5 cases. Seven patients presented with mechanical-type pain, while 2 patients had an elevated temperature at diagnosis. A contiguous infection between the upper airways and the cervical spine was present in 4 patients. One patient presented with concomitant candidemia. Candida albicans, Candida parapsilosis, and Candida glabrata were cultured in 3 of 9 cases respectively. Eight of 9 were treated with azole-based therapy. Patients were followed for an average of 20 months (range 1 - 75 months). The cumulative incidence of success was 66% ± 19% at 1 year and 55% ± 20% at 2 years of follow-up. Conclusions: CVO presents insidiously and is associated with a long duration of symptoms. It most frequently affects the cervical spine and is associated with a poor outcome.展开更多
ALK-negative anaplastic large cell lymphoma (ALCL, ALK-) is a CD30+ T-cell neoplasm composed of large lymphoid cells with abundant cytoplasm and pleomorphic nuclei that lacks expression of ALK protein. We describe a c...ALK-negative anaplastic large cell lymphoma (ALCL, ALK-) is a CD30+ T-cell neoplasm composed of large lymphoid cells with abundant cytoplasm and pleomorphic nuclei that lacks expression of ALK protein. We describe a case of ALCL, ALK-with primary involvement of the rectum in a 37 year old man, where the original diagnosis was established based on a colonoscopic biopsy. T-cell lymphomas are rare in the colorectal area and besides ALCL, their differential diagnosis includes enteropathic T-cell lymphoma, peripheral T-cell lymphoma, not otherwise specified, NK/T cell lymphoma, or NK-cell enteropathy. In addition, syncytial variant of classical Hodgkin lymphoma or a pleomorphic CD30-positive diffuse large B-cell lymphoma should also be ruled out. We discuss pitfalls of the differential diagnosis and review the literature of anaplastic large cell lymphoma in the gastrointestinal tract. Correct diagnosis of ALCL in the colon is important to avoid a colorectal surgery for an assumed adenocarcinoma, and to open the possibility for lymphoma-directed chemotherapy.展开更多
BACKGROUND Chronic hepatitis B virus(HBV)and hepatitis C virus(HCV)infections are known risk factors for liver disease,cirrhosis and hepatocellular carcinoma(HCC).There is substantial global variation in HBV and HCV p...BACKGROUND Chronic hepatitis B virus(HBV)and hepatitis C virus(HCV)infections are known risk factors for liver disease,cirrhosis and hepatocellular carcinoma(HCC).There is substantial global variation in HBV and HCV prevalence resulting in variations in cirrhosis and HCC.We previously reported high prevalence of HBV and HCV infections in Somali immigrants seen at an academic medical center in Minnesota.AIM To determine the prevalence of chronic viral hepatitis in Somali immigrants in Minnesota through a community-based screening program.METHODS We conducted a prospective community-based participatory research study in the Somali community in Minnesota in partnership with community advisory boards,community clinics and local mosques between November 2010 and December 2015(data was analyzed in 2020).Serum was tested for hepatitis B surface antigen,hepatitis B core antibody,hepatitis B surface antibody and anti-HCV antibody.RESULTS Of 779 participants,15.4%tested positive for chronic HBV infection,50.2%for prior exposure to HBV and 7.6%for chronic HCV infection.Calculated age-adjusted frequencies in males and females for chronic HBV were 12.5%and 11.6%;for prior exposure to HBV were 44.8%and 41.3%;and for chronic HCV were 6.7%and 5.7%,respectively.Seven participants developed incident HCC during follow up.CONCLUSION Chronic HBV and HCV are major risk factors for liver disease and HCC among Somali immigrants,with prevalence of both infections substantially higher than in the general United States population.Community-based screening is essential for identifying and providing health education and linkage to care for diagnosed patients.展开更多
<span style="font-family:""><span style="font-family:Verdana;">Primary cardiac lymphoma (PCL) is a rare entity that comprises only 1% - 2% of all cardiac tumors. Due to their scarc...<span style="font-family:""><span style="font-family:Verdana;">Primary cardiac lymphoma (PCL) is a rare entity that comprises only 1% - 2% of all cardiac tumors. Due to their scarcity and variable clinical presentation, early diagnosis is challenging. In this series, three cases of PCL from a single institution are described, which highlight the spectrum of presenting features and emphasize common principles. In the first case, a 73-year-old male who presented with dyspnea was found to have a 12.1 cm mass in the right ventricle. Biopsy via cardiac catheterization revealed diffuse large B cell ly</span><span style="font-family:Verdana;">mphoma (DLBCL). He was treated with chemoimmunotherapy and s</span><span style="font-family:Verdana;">urvived for two months. The second case describes a 55-year-old female who presented with chest pain. Imaging revealed a 3.1 cm right atrial mass and bilateral pleural effusions, with cytology from the latter demonstrating DLBCL. She was lost to follow up after three cycles of chemoimmunotherapy. In the last case, an 80-year-old female presented with weakness. A 4.0 cm mass was discovered in the right atrium and the patient expired shortly after admission. Autopsy confirmed the diagnosis of DLBCL. These case summaries are follo</span><span style="font-family:Verdana;">wed by a review of the clinical presentation, diagnostic approach, an</span><span style="font-family:Verdana;">d treatment outcomes of PCL.展开更多
The association between type 2 diabetes mellitus(DM)and colorectal cancer(CRC)has been thoroughly investigated and reports have demonstrated that the risk of CRC is increased in DM patients.The association between DM ...The association between type 2 diabetes mellitus(DM)and colorectal cancer(CRC)has been thoroughly investigated and reports have demonstrated that the risk of CRC is increased in DM patients.The association between DM and the survival of patients with CRC is controversial.Evidence suggests that metformin with its anti-inflammatory effects is a protective factor against the development of CRC among DM patients and that metformin therapy is associated with a better prognosis in patients with DM.In our cohort,we did not find any associations between the presence of DM or metformin and cancer specific survival or any relation to plasma levels of a panel of 40 inflammatory factors and irisin.On the other hand,we identified that the insulin-like growth factor binding protein 7 single nucleotide polymorphism rs2041437 was associated with DM in CRC patients.The dominance of the T bearing genotypes in patients with DM was statistically significant(P=0.038),with an odds ratio of 1.66(95%confidence interval:1.03-2.69).展开更多
The androgen receptor(AR)is a member of the steroid receptor family of transcription factors.These ligandregulated transcription factors have C-terminal ligand binding domains with low nanomolar affinities for their c...The androgen receptor(AR)is a member of the steroid receptor family of transcription factors.These ligandregulated transcription factors have C-terminal ligand binding domains with low nanomolar affinities for their cognate steroid ligands.The steroid ligands for AR are the androgens testosterone and dihydrotestosterone(DHT),which are the most abundant sex hormones in the circulation of males.展开更多
In the 21st century,the determination of alert thresholds remains the most challenging and controversial issue in clinical pediatrics.Pre-analytical,analytical,and postanalytical matters will consolidate or undermine ...In the 21st century,the determination of alert thresholds remains the most challenging and controversial issue in clinical pediatrics.Pre-analytical,analytical,and postanalytical matters will consolidate or undermine the fate of any laboratory process.Pre-analytical issues need to be cleared off before the laboratory physician can dispatch the result to the pediatrician in charge.Once it is cleared off,the classification of essential laboratory results is paramount.It is more than an academic exercise and may be subdivided in the order of priority we handle it to inform promptly and safely the primary physicians.Currently,we are applying new modes of making sure relevant information is transmitted without interrupting the standard workflow of the primary physicians in charge for the child,who eventually need a fast line of action for results that may be lifethreatening.展开更多
BACKGROUND Glomerulopathy with fibrillary deposits is not uncommon in routine nephropathology practice,with amyloidosis and fibrillary glomerulonephritis being the two most frequently encountered entities.Renal amyloi...BACKGROUND Glomerulopathy with fibrillary deposits is not uncommon in routine nephropathology practice,with amyloidosis and fibrillary glomerulonephritis being the two most frequently encountered entities.Renal amyloid heavy and light chain(AHL)is relatively uncommon and its biopsy diagnosis is usually limited to cases that show strong equivalent staining for a single immunoglobulin(Ig)heavy chain and a single light chain,further supported by mass spectrometry(MS)and serum studies for monoclonal protein.But polyclonal light chain staining can pose a challenge.CASE SUMMARY Herein we present a challenging case of renal AHL with polyclonal and polytypic Ig gamma(IgG)staining pattern by immunofluorescence.The patient is a 62-yearold Caucasian male who presented to an outside institution with a serum creatinine of up to 8.1 mg/dL and nephrotic range proteinuria.Despite the finding of a polyclonal and polytypic staining pattern on immunofluorescence,ultrastructural study of the renal biopsy demonstrated the presence of fibrils with a mean diameter of 10 nm.Congo red was positive while DNAJB9 was negative.MS suggested a diagnosis of amyloid AHL type with IgG and lambda,but kappa light chains were also present supporting the immunofluorescence staining results.Serum immunofixation studies demonstrated IgG lambda monoclonal spike.The patient was started on chemotherapy.The chronic renal injury however was quite advanced and he ended up needing dialysis shortly after.CONCLUSION Tissue diagnosis of AHL amyloid can be tricky.Thorough confirmation using other available diagnostic techniques is recommended in such cases.展开更多
In today's healthcare,clinical laboratory medicine stands as a cornerstone of patient care,providing vital diagnostic insights that inform decisions in disease management.Yet,within this crucial field,a dichotomy ...In today's healthcare,clinical laboratory medicine stands as a cornerstone of patient care,providing vital diagnostic insights that inform decisions in disease management.Yet,within this crucial field,a dichotomy persists between two predominant models of laboratory testing to support clinical practice:point-of-care testing(PoCT)and central laboratory testing[1].This schism,while born of practical necessity and evolving technology,presents both opportunities and challenges that warrant closer examination.展开更多
AIM: To explore the contribution of AXIN1, AXIN2 and beta-catenin, components of Wnt signaling pathway, to the carcinogenesis of gastric cancer (GC), we examined AXIN1, AXIN2 exon7 and CTNNB1 (encoding beta- catenin) ...AIM: To explore the contribution of AXIN1, AXIN2 and beta-catenin, components of Wnt signaling pathway, to the carcinogenesis of gastric cancer (GC), we examined AXIN1, AXIN2 exon7 and CTNNB1 (encoding beta- catenin) exon3 mutations in 70 GCs. METHODS: The presence of mutations was identified by polymerase chain reaction (PCR)-based denaturing high-performance liquid chromatography and direct DNA sequencing. Beta-catenin expression was detected by immunohistochemical analysis. RESULTS: Among the 70 GCs, 5 (7.1%) had mutations in one or two of these three components. A frameshift mutation (1 bp deletion) in exon7 of AXIN2 was found in one case. Four cases, including the case with a mutation in AXIN2, had frameshift mutations and missense mutations in AXIN1. Five single nucleotide polymorphisms (SNPs), 334 C>T, 874 C>T, 1396 G>A, 1690 C>T and 1942 T>G, were identified in AXIN1. A frameshift mutation (27 bp deletion) spanning exon3 of CTNNB1 was observed in one case. All four cases with mutations in AXIN1 and AXIN2 showed nuclear beta- catenin expression. CONCLUSION: These data indicate that the mutationsin AXIN1 and AXIN2 may contribute to gastric carcino- genesis.展开更多
AIM To assess the performance of BALAD, BALAD-2 and their component biomarkers in predicting outcome of hepatocellular carcinoma(HCC) patients after liver transplant.METHODS BALAD score and BALAD-2 class are derived f...AIM To assess the performance of BALAD, BALAD-2 and their component biomarkers in predicting outcome of hepatocellular carcinoma(HCC) patients after liver transplant.METHODS BALAD score and BALAD-2 class are derived from bilirubin, albumin, alpha-fetoprotein(AFP), Lens culinaris agglutinin-reactive AFP(AFP-L3), and des-gammacarboxyprothrombin(DCP). Pre-transplant AFP, AFP-L3 and DCP were measured in 113 patients transplanted for HCC from 2000 to 2008. Hazard ratios(HR) for recurrence and death were calculated. Univariate and multivariate regression analyses were conducted. C-statistics were used to compare biomarker-based to predictive models. RESULTS During a median follow-up of 12.2 years, 38 patients recurred and 87 died. The HRs for recurrence in patients with elevated AFP, AFP-L3, and DCP defined by BALAD cut-off values were 2.42(1.18-5.00), 1.86(0.98-3.52), and 2.83(1.42-5.61), respectively. For BALAD, the HRs for recurrence and death per unit increased score were 1.48(1.15-1.91) and 1.59(1.28-1.97). For BALAD-2, the HRs for recurrence and death per unit increased class were 1.45(1.06-1.98) and 1.38(1.09-1.76). For recurrence prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs. 0.64, 0.61, 0.53, and 0.53 for BALAD, BALAD-2, Milan, and UCSF, respectively. Similarly, for death prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs 0.65,0.61, 0.52, and 0.50 for BALAD, BALAD-2, Milan, and UCSF. A new model combining biomarkers with tumor size at the time of transplant(S-LAD) demonstrated the highest predictive capability with c-statistics of 0.71 and 0.69 for recurrence and death. CONCLUSION BALAD and BALAD-2 are valid in transplant HCC patients, but less predictive than the three biomarkers in combination or the three biomarkers in combination with maximal tumor diameter(S-LAD).展开更多
Alzheimer＇s disease, a progressive neurodegenerative illness, is the most common torm or dementia. So far, there is neither an effective prevention nor a cure for AIzheimer＇s disease. In recent decades, stem cell th...Alzheimer＇s disease, a progressive neurodegenerative illness, is the most common torm or dementia. So far, there is neither an effective prevention nor a cure for AIzheimer＇s disease. In recent decades, stem cell therapy has been one of the most promising treatments for Alzheimer＇s disease patients. This article aims to summarize the current progress in the stem cell treatments for Alzheimer＇s disease from an experiment to a clinical research.展开更多
AIMTo determine the effect of overexpression of fibrinogen-like protein 2 (FGL2) on regulatory T cell (Treg) and effector T (Teff) cell function on T cell-induced colitis in Rag1<sup>-/-</sup> mice.METHODS...AIMTo determine the effect of overexpression of fibrinogen-like protein 2 (FGL2) on regulatory T cell (Treg) and effector T (Teff) cell function on T cell-induced colitis in Rag1<sup>-/-</sup> mice.METHODSTreg and Teff cells from fgl2<sup>-/-</sup>, fgl2<sup>+/+</sup>, and fgl2<sup>Tg</sup> mice were purified by FACS. They were studied in vitro for immunosuppressive activity and cell proliferation and in vivo for their effects on the development and prevention of T cell-induced colitis in Rag1<sup>-/-</sup> mice.RESULTSIn vitro, fgl2<sup>Tg</sup> Treg had enhanced immunosuppressive activity, and fgl2<sup>Tg</sup> Teff had reduced proliferation to alloantigen stimulation. Transfer of Teff from C57Bl/6J mice (fgl2<sup>+/+</sup>) into Rag1<sup>-/-</sup> mice produced both clinical and histologic colitis with dense infiltrates of CD3<sup>+</sup> T cells, crypt abscesses and loss of goblet cells. Fgl2<sup>Tg</sup> Treg prevented the development of T cell-induced colitis, whereas fgl2<sup>+/+</sup> and fgl2<sup>-/-</sup> Treg were only partially protective. In mice that received fgl2<sup>Tg</sup> Treg, the ratio of Foxp3<sup>+</sup> to CD3<sup>+</sup> cells was increased both in the colon and in mesenteric lymph nodes, and Teff cell proliferation as determined by staining with Ki67 was reduced. Teff cells from fgl2<sup>Tg</sup> mice did not produce colitis.CONCLUSIONHere we show that fgl2<sup>Tg</sup> Teff are hypoproliferative and do not induce colitis. We further demonstrate that fgl2<sup>Tg</sup> Treg prevent colitis in contrast to fgl2<sup>+/+</sup> Treg, which were only partially protective. These studies collectively provide a rationale for exploring the use of FGL2 or Treg expressing high levels of FGL2 in the treatment of inflammatory bowel disease.展开更多
基金Supported by The National Institutes of Health,No.R01HL147155 and No.R01AG060920.
文摘BACKGROUND There is concern regarding potential long-term cardiotoxicity with systemic distribution of metals in total joint arthroplasty(TJA)patients.AIM To determine the association of commonly used implant metals with echocardiographic measures in TJA patients.METHODS The study comprised 110 TJA patients who had a recent history of high chromium,cobalt or titanium concentrations.Patients underwent two-dimensional,three-dimensional,Doppler and speckle-strain transthoracic echocardiography and a blood draw to measure metal concentrations.Age and sex-adjusted linear and logistic regression models were used to examine the association of metal concentrations(exposure)with echocardiographic measures(outcome).RESULTS Higher cobalt concentrations were associated with increased left ventricular end-diastolic volume(estimate 5.09;95%CI:0.02-10.17)as well as left atrial and right ventricular dilation,particularly in men but no changes in cardiac function.Higher titanium concentrations were associated with a reduction in left ventricle global longitudinal strain(estimate 0.38;95%CI:0.70 to 0.06)and cardiac index(estimate 0.08;95%CI,-0.15 to-0.01).CONCLUSION Elevated cobalt and titanium concentrations may be associated with structural and functional cardiac changes in some patients.Longitudinal studies are warranted to better understand the systemic effects of metals in TJA patients.
基金Supported by Chilean Government Through the Fondo Nacional de Desarrollo Científico y Tecnológico,No.1200227,No.1191183 and No.1191145Comisión Nacional de Investigación Científica y Tecnológica (CONICYT,CARE Chile UC),No.AFB170005European Union’s Horizon 2020 Research,No.825510
文摘BACKGROUND Coronavirus disease 2019(COVID-19)disease can frequently affect the liver.Data on hepatic histopathological findings in COVID-19 is scarce.AIM To characterize hepatic pathological findings in patients with COVID-19.METHODS We conducted a systematic review with meta-analysis registered on PROSPERO(CRD42020192813),following PRISMA guidelines.Eligible trials were those including patients of any age and COVID-19 diagnosis based on a molecular test.Histopathological reports from deceased COVID-19 patients undergoing autopsy or liver biopsy were reviewed.Articles including less than ten patients were excluded.Proportions were pooled using random-effects models.Q statistic and I2 were used to assess heterogeneity and levels of evidence,respectively.RESULTS We identified 18 studies from 7 countries;all were case reports and case series from autopsies.All the patients were over 15 years old,and 67.2%were male.We performed a meta-analysis of 5 studies,including 116 patients.Pooled prevalence estimates of liver histopathological findings were hepatic steatosis 55.1%[95%confidence interval(CI):46.2-63.8],congestion of hepatic sinuses 34.7%(95%CI:7.9-68.4),vascular thrombosis 29.4%(95%CI:0.4-87.2),fibrosis 20.5%(95%CI:0.6-57.9),Kupffer cell hyperplasia 13.5%(95%CI:0.6-54.3),portal inflammation 13.2%(95%CI:0.1-48.8),and lobular inflammation 11.6%(95%CI:0.3-35.7).We also identified the presence of venous outflow obstruction,phlebosclerosis of the portal vein,herniated portal vein,periportal abnormal vessels,hemophagocytosis,and necrosis.CONCLUSION We found a high prevalence of hepatic steatosis and vascular thrombosis as major histological liver features.Other frequent findings included portal and lobular inflammation and Kupffer cell hyperplasia or proliferation.Further studies are needed to establish the mechanisms and implications of these findings.
基金Supported by The Natural Sciences and Engineering Research Council of Canada,the Broad Foundation,the Canadian Institutes of Health Research and The Alberta Livestock and Meat Agency
文摘AIM: To investigate whether accelerated catabolism of ganglioside and decreased ganglioside content contribute to the etiology of pro-inflammatory intestinal disease. METHODS: Intestinal mucosa from terminal ileum or colon was obtained from patients with ulcerative colitis or inflammatory Crohn's disease(n = 11) undergoing bowel resection and compared to control samples of normal intestine from patients with benign colon polyps(n = 6) and colorectal cancer(n = 12) in this observational case-control study. Gangliosides and phospholipids of intestinal mucosa were characterized by class and ceramide or fatty acid composition using liquid chromatography triple-quad mass spectrometry. Content and composition of ganglioside classes GM1, GM3, GD3, GD1 a, GT1 and GT3 were compared among subject groups. Content and composition of phospholipid classes phosphatidylcholine(PC) and phosphatidylethanolamine were compared among subject groups. Unsaturation index of individual ganglioside and phospholipid classes was computed and compared among subject groups. Ganglioside catabolism enzymes beta-hexosaminidase A(HEXA) and sialidase-3(NEU3) were measured in intestinal mucosa using western blot and compared among subject groups. RESULTS: Relative GM3 ganglioside content was 2-fold higher(P < 0.05) in intestine from patients with inflammatory bowel disease(IBD) compared to control intestine. The quantity of GM3 and ratio of GM3/GD3 was also higher in IBD intestine than control tissue(P < 0.05). Control intestine exhibited 3-fold higher(P < 0.01) relative GD1 a ganglioside content than IBD intestine. GD3 and GD1 a species of ganglioside containing three unsaturated bonds were present in control intestine, but were not detected in IBD intestine. The relative content of PC containing more than two unsaturated bonds was 30% lower in IBD intestine than control intestine(P < 0.05). The relative content of HEXA in IBD intestine was increased 1.7-fold(P < 0.05) and NEU3 was increased 8.3-fold(P < 0.01) compared to normal intestine. Intestinal mucosa in IBD is characterized by increased GM3 content, decreased GD1 a, and a reduction in polyunsaturated fatty acid constituents in GD3, GD1 a and PC.CONCLUSION: This study suggests a new paradigm by proposing that IBD occurs as a consequence of increased metabolism of specific gangliosides.
基金supported by the Canadian Institutes of Health Research (grant number 115068)。
文摘Diffuse idiopathic skeletal hyperostosis(DISH) is a prevalent noninflammatory spondyloarthropathy characterized by ectopic mineral formation along the anterolateral aspect of the vertebral column, yet little is known about its underlying pathogenesis. Our objective was to evaluate the histopathological features and composition of ectopic mineral within spinal tissues affected by DISH in humans. Thoracic spine segments from six embalmed cadaveric donors(one female and five males;median age 82 years)meeting the radiographic diagnostic criteria for DISH were evaluated using radiological, histological, and physical analyses. Overall,the histological features of ectopic mineralization at individual motion segments were heterogeneous, including regions of heterotopic ossification and dystrophic calcification. Heterotopic ossifications were characterized by woven and lamellar bone,multifocal areas of metaplastic cartilage, and bony bridges along the anterior aspect of the intervertebral disc space. Dystrophic calcifications were characterized by an amorphous appearance, a high content of calcium and phosphorus, an X-ray diffraction pattern matching that of hydroxyapatite, and radiodensities exceeding that of cortical bone. Dystrophic calcifications were found within the anterior longitudinal ligament and annulus fibrosus in motion segments both meeting and not meeting the radiographic criteria for DISH. In summary, our findings indicate that in DISH, ectopic mineral forms along the anterior aspect of the spine by both heterotopic ossification and dystrophic calcification of fibrocartilaginous tissues. Although both types of ectopic mineralization are captured by current radiographic criteria for DISH, dystrophic calcification may reflect a distinct disease process or an early stage in the pathogenesis of DISH.
基金Medical Research Council of Southeast Sweden(FORSS)and Division of Medical Diagnostics(Futurum),Region Jönköping County,Sweden.
文摘BACKGROUND Leukocytes,such as T cells and macrophages,play an important role in tumorigenesis.CC chemokine ligand(CCL)4,which is produced by lymphocytes and macrophages,has been found to be expressed in the mucosa of the gastrointestinal tract and is a potent chemoattractant for various leukocytes.AIM To examine CCL4 expression and its genetic polymorphism rs10491121 in patients with colorectal cancer(CRC)and evaluate their prognostic significance.METHODS Luminex technology was used to determine CCL4 Levels in CRC tissue(n=98),compared with paired normal tissue,and in plasma from patients with CRC(n=103),compared with healthy controls(n=97).Included patients had undergone surgical resection for primary colorectal adenocarcinomas between 1996 and 2019 at the Department of Surgery,Ryhov County Hospital,Jönköping,Sweden.Reverse transcription quantitative PCR was used to investigate the CCL4 gene expression in CRC tissue(n=101).Paired normal tissue and TaqMan single nucleotide polymorphism assays were used for the CCL4 rs10491121 polymorphism in 610 CRC patients and 409 healthy controls.RESULTS The CCL4 protein and messenger RNA expression levels were higher in CRC tissue than in normal paired tissue(90%,P<0.001 and 45%,P<0.05,respectively).CRC tissue from patients with localized disease had 2.8-fold higher protein expression levels than that from patients with disseminated disease.Low CCL4 protein expression levels in CRC tissue were associated with a 30%lower cancer-specific survival rate in patients(P<0.01).The level of plasma CCL4 was 11%higher in CRC patients than in healthy controls(P<0.05)and was positively correlated(r=0.56,P<0.01)with the CCL4 protein level in CRC tissue.The analysis of CCL4 gene polymorphism rs10491121 showed a difference(P<0.05)between localized disease and disseminated disease in the right colon,with a dominance of allele A in localized disease.Moreover,the rate of the A allele was higher among CRC patients with mucinous cancer than among those with nonmucinous cancer.CONCLUSION The present study indicates that the CRC tissue levels of CCL4 and CCL4 gene polymorphism rs10491121,particularly in the right colon,are associated with clinical outcome in CRC patients.
文摘AIM: To investigate a classification of endocytoscopy (ECS) images in Barrett’s esophagus (BE) and evaluate its diagnostic performance and interobserver variability.
基金supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health (No. R01NS102360)。
文摘It was hypothesized that mesenchymal stem cells(MSCs) could provide necessary trophic factors when seeded onto the surfaces of commonly used nerve graft substitutes. We aimed to determine the gene expression of MSCs when influenced by Avance■ Nerve Grafts or Neura Gen■ Nerve Guides. Human adipose-derived MSCs were cultured and dynamically seeded onto 30 Avance■ Nerve Grafts and 30 Neura Gen■ Nerve Guides for 12 hours. At six time points after seeding, quantitative polymerase chain reaction analyses were performed for five samples per group. Neurotrophic [nerve growth factor(NGF), glial cell line-derived neurotrophic factor(GDNF), pleiotrophin(PTN), growth associated protein 43(GAP43) and brain-derived neurotrophic factor(BDNF)], myelination [peripheral myelin protein 22(PMP22) and myelin protein zero(MPZ)], angiogenic [platelet endothelial cell adhesion molecule 1(PECAM1/CD31) and vascular endothelial cell growth factor alpha(VEGFA)], extracellular matrix(ECM) [collagen type alpha I(COL1A1), collagen type alpha III(COL3A1), Fibulin 1(FBLN1) and laminin subunit beta 2(LAMB2)] and cell surface marker cluster of differentiation 96(CD96) gene expression was quantified. Unseeded Avance■ Nerve Grafts and Neura Gen■ Nerve Guides were used to evaluate the baseline gene expression, and unseeded MSCs provided the baseline gene expression of MSCs. The interaction of MSCs with the Avance■ Nerve Grafts led to a short-term upregulation of neurotrophic(NGF, GDNF and BDNF), myelination(PMP22 and MPZ) and angiogenic genes(CD31 and VEGFA) and a long-term upregulation of BDNF, VEGFA and COL1A1. The interaction between MSCs and the Neura Gen■ Nerve Guide led to short term upregulation of neurotrophic(NGF, GDNF and BDNF) myelination(PMP22 and MPZ), angiogenic(CD31 and VEGFA), ECM(COL1A1) and cell surface(CD96) genes and long-term upregulation of neurotrophic(GDNF and BDNF), angiogenic(CD31 and VEGFA), ECM genes(COL1A1, COL3A1, and FBLN1) and cell surface(CD96) genes. Analysis demonstrated MSCs seeded onto Neura Gen■ Nerve Guides expressed significantly higher levels of neurotrophic(PTN), angiogenic(VEGFA) and ECM(COL3A1, FBLN1) genes in the long term period compared to MSCs seeded onto Avance■ Nerve Grafts. Overall, the interaction between human MSCs and both nerve graft substitutes resulted in a significant upregulation of the expression of numerous genes important for nerve regeneration over time. The in vitro interaction of MSCs with the Neura Gen■ Nerve Guide was more pronounced, particularly in the long term period(> 14 days after seeding). These results suggest that MSC-seeding has potential to be applied in a clinical setting, which needs to be confirmed in future in vitro and in vivo research.
文摘Objective: To describe the demographics and outcome of patients with candidal vertebral osteomyelitis (CVO). CVO is a rare and frequently misdiagnosed condition. It may lead to destruction of the vertebral bodies, spinal cord compression and neurological deficits. Methods: The medical records of all patients diagnosed with CVO at our institution between 01/01/1990-12/31/2009 were reviewed. The cumulative probability of treatment success was assessed by the Kaplan-Meier survival method. Patients were followed until death, failure, or loss of follow-up. Results: Nine patients developed CVO during the 20 year study period. The cervical spine was involved in 5 cases. Seven patients presented with mechanical-type pain, while 2 patients had an elevated temperature at diagnosis. A contiguous infection between the upper airways and the cervical spine was present in 4 patients. One patient presented with concomitant candidemia. Candida albicans, Candida parapsilosis, and Candida glabrata were cultured in 3 of 9 cases respectively. Eight of 9 were treated with azole-based therapy. Patients were followed for an average of 20 months (range 1 - 75 months). The cumulative incidence of success was 66% ± 19% at 1 year and 55% ± 20% at 2 years of follow-up. Conclusions: CVO presents insidiously and is associated with a long duration of symptoms. It most frequently affects the cervical spine and is associated with a poor outcome.
文摘ALK-negative anaplastic large cell lymphoma (ALCL, ALK-) is a CD30+ T-cell neoplasm composed of large lymphoid cells with abundant cytoplasm and pleomorphic nuclei that lacks expression of ALK protein. We describe a case of ALCL, ALK-with primary involvement of the rectum in a 37 year old man, where the original diagnosis was established based on a colonoscopic biopsy. T-cell lymphomas are rare in the colorectal area and besides ALCL, their differential diagnosis includes enteropathic T-cell lymphoma, peripheral T-cell lymphoma, not otherwise specified, NK/T cell lymphoma, or NK-cell enteropathy. In addition, syncytial variant of classical Hodgkin lymphoma or a pleomorphic CD30-positive diffuse large B-cell lymphoma should also be ruled out. We discuss pitfalls of the differential diagnosis and review the literature of anaplastic large cell lymphoma in the gastrointestinal tract. Correct diagnosis of ALCL in the colon is important to avoid a colorectal surgery for an assumed adenocarcinoma, and to open the possibility for lymphoma-directed chemotherapy.
基金Supported by the Mayo Clinic Center for Clinical and Translational Science from the National Center for Advancing Translational Sciences (5UL1TR000135-10)the Mayo Clinic Hepatobiliary SPORE from the National Cancer Institute (5P50CA210964-04)+1 种基金the Mayo Clinic Center for Cell Signaling in Gastroenterology (5P30DK084567-14)Gilead Sciences,Inc.(IN-US-174-0230)
文摘BACKGROUND Chronic hepatitis B virus(HBV)and hepatitis C virus(HCV)infections are known risk factors for liver disease,cirrhosis and hepatocellular carcinoma(HCC).There is substantial global variation in HBV and HCV prevalence resulting in variations in cirrhosis and HCC.We previously reported high prevalence of HBV and HCV infections in Somali immigrants seen at an academic medical center in Minnesota.AIM To determine the prevalence of chronic viral hepatitis in Somali immigrants in Minnesota through a community-based screening program.METHODS We conducted a prospective community-based participatory research study in the Somali community in Minnesota in partnership with community advisory boards,community clinics and local mosques between November 2010 and December 2015(data was analyzed in 2020).Serum was tested for hepatitis B surface antigen,hepatitis B core antibody,hepatitis B surface antibody and anti-HCV antibody.RESULTS Of 779 participants,15.4%tested positive for chronic HBV infection,50.2%for prior exposure to HBV and 7.6%for chronic HCV infection.Calculated age-adjusted frequencies in males and females for chronic HBV were 12.5%and 11.6%;for prior exposure to HBV were 44.8%and 41.3%;and for chronic HCV were 6.7%and 5.7%,respectively.Seven participants developed incident HCC during follow up.CONCLUSION Chronic HBV and HCV are major risk factors for liver disease and HCC among Somali immigrants,with prevalence of both infections substantially higher than in the general United States population.Community-based screening is essential for identifying and providing health education and linkage to care for diagnosed patients.
文摘<span style="font-family:""><span style="font-family:Verdana;">Primary cardiac lymphoma (PCL) is a rare entity that comprises only 1% - 2% of all cardiac tumors. Due to their scarcity and variable clinical presentation, early diagnosis is challenging. In this series, three cases of PCL from a single institution are described, which highlight the spectrum of presenting features and emphasize common principles. In the first case, a 73-year-old male who presented with dyspnea was found to have a 12.1 cm mass in the right ventricle. Biopsy via cardiac catheterization revealed diffuse large B cell ly</span><span style="font-family:Verdana;">mphoma (DLBCL). He was treated with chemoimmunotherapy and s</span><span style="font-family:Verdana;">urvived for two months. The second case describes a 55-year-old female who presented with chest pain. Imaging revealed a 3.1 cm right atrial mass and bilateral pleural effusions, with cytology from the latter demonstrating DLBCL. She was lost to follow up after three cycles of chemoimmunotherapy. In the last case, an 80-year-old female presented with weakness. A 4.0 cm mass was discovered in the right atrium and the patient expired shortly after admission. Autopsy confirmed the diagnosis of DLBCL. These case summaries are follo</span><span style="font-family:Verdana;">wed by a review of the clinical presentation, diagnostic approach, an</span><span style="font-family:Verdana;">d treatment outcomes of PCL.
基金Supported by the Medical Research Council of Southeast Sweden,No.FORSS-931897the Division of Medical Diagnostics of Region Jönköping County,No.Futurum-970572.
文摘The association between type 2 diabetes mellitus(DM)and colorectal cancer(CRC)has been thoroughly investigated and reports have demonstrated that the risk of CRC is increased in DM patients.The association between DM and the survival of patients with CRC is controversial.Evidence suggests that metformin with its anti-inflammatory effects is a protective factor against the development of CRC among DM patients and that metformin therapy is associated with a better prognosis in patients with DM.In our cohort,we did not find any associations between the presence of DM or metformin and cancer specific survival or any relation to plasma levels of a panel of 40 inflammatory factors and irisin.On the other hand,we identified that the insulin-like growth factor binding protein 7 single nucleotide polymorphism rs2041437 was associated with DM in CRC patients.The dominance of the T bearing genotypes in patients with DM was statistically significant(P=0.038),with an odds ratio of 1.66(95%confidence interval:1.03-2.69).
文摘The androgen receptor(AR)is a member of the steroid receptor family of transcription factors.These ligandregulated transcription factors have C-terminal ligand binding domains with low nanomolar affinities for their cognate steroid ligands.The steroid ligands for AR are the androgens testosterone and dihydrotestosterone(DHT),which are the most abundant sex hormones in the circulation of males.
文摘In the 21st century,the determination of alert thresholds remains the most challenging and controversial issue in clinical pediatrics.Pre-analytical,analytical,and postanalytical matters will consolidate or undermine the fate of any laboratory process.Pre-analytical issues need to be cleared off before the laboratory physician can dispatch the result to the pediatrician in charge.Once it is cleared off,the classification of essential laboratory results is paramount.It is more than an academic exercise and may be subdivided in the order of priority we handle it to inform promptly and safely the primary physicians.Currently,we are applying new modes of making sure relevant information is transmitted without interrupting the standard workflow of the primary physicians in charge for the child,who eventually need a fast line of action for results that may be lifethreatening.
文摘BACKGROUND Glomerulopathy with fibrillary deposits is not uncommon in routine nephropathology practice,with amyloidosis and fibrillary glomerulonephritis being the two most frequently encountered entities.Renal amyloid heavy and light chain(AHL)is relatively uncommon and its biopsy diagnosis is usually limited to cases that show strong equivalent staining for a single immunoglobulin(Ig)heavy chain and a single light chain,further supported by mass spectrometry(MS)and serum studies for monoclonal protein.But polyclonal light chain staining can pose a challenge.CASE SUMMARY Herein we present a challenging case of renal AHL with polyclonal and polytypic Ig gamma(IgG)staining pattern by immunofluorescence.The patient is a 62-yearold Caucasian male who presented to an outside institution with a serum creatinine of up to 8.1 mg/dL and nephrotic range proteinuria.Despite the finding of a polyclonal and polytypic staining pattern on immunofluorescence,ultrastructural study of the renal biopsy demonstrated the presence of fibrils with a mean diameter of 10 nm.Congo red was positive while DNAJB9 was negative.MS suggested a diagnosis of amyloid AHL type with IgG and lambda,but kappa light chains were also present supporting the immunofluorescence staining results.Serum immunofixation studies demonstrated IgG lambda monoclonal spike.The patient was started on chemotherapy.The chronic renal injury however was quite advanced and he ended up needing dialysis shortly after.CONCLUSION Tissue diagnosis of AHL amyloid can be tricky.Thorough confirmation using other available diagnostic techniques is recommended in such cases.
文摘In today's healthcare,clinical laboratory medicine stands as a cornerstone of patient care,providing vital diagnostic insights that inform decisions in disease management.Yet,within this crucial field,a dichotomy persists between two predominant models of laboratory testing to support clinical practice:point-of-care testing(PoCT)and central laboratory testing[1].This schism,while born of practical necessity and evolving technology,presents both opportunities and challenges that warrant closer examination.
文摘AIM: To explore the contribution of AXIN1, AXIN2 and beta-catenin, components of Wnt signaling pathway, to the carcinogenesis of gastric cancer (GC), we examined AXIN1, AXIN2 exon7 and CTNNB1 (encoding beta- catenin) exon3 mutations in 70 GCs. METHODS: The presence of mutations was identified by polymerase chain reaction (PCR)-based denaturing high-performance liquid chromatography and direct DNA sequencing. Beta-catenin expression was detected by immunohistochemical analysis. RESULTS: Among the 70 GCs, 5 (7.1%) had mutations in one or two of these three components. A frameshift mutation (1 bp deletion) in exon7 of AXIN2 was found in one case. Four cases, including the case with a mutation in AXIN2, had frameshift mutations and missense mutations in AXIN1. Five single nucleotide polymorphisms (SNPs), 334 C>T, 874 C>T, 1396 G>A, 1690 C>T and 1942 T>G, were identified in AXIN1. A frameshift mutation (27 bp deletion) spanning exon3 of CTNNB1 was observed in one case. All four cases with mutations in AXIN1 and AXIN2 showed nuclear beta- catenin expression. CONCLUSION: These data indicate that the mutationsin AXIN1 and AXIN2 may contribute to gastric carcino- genesis.
基金Mayo Clinic Center for Clinical and Translational Science(CCATS)No.NCATS 1UL1TR002377-01+1 种基金Mayo Clinic Center for Cell Signaling in Gastroenterology,No.NIDDK P30DK084567-09Wako Life Sciences,Inc
文摘AIM To assess the performance of BALAD, BALAD-2 and their component biomarkers in predicting outcome of hepatocellular carcinoma(HCC) patients after liver transplant.METHODS BALAD score and BALAD-2 class are derived from bilirubin, albumin, alpha-fetoprotein(AFP), Lens culinaris agglutinin-reactive AFP(AFP-L3), and des-gammacarboxyprothrombin(DCP). Pre-transplant AFP, AFP-L3 and DCP were measured in 113 patients transplanted for HCC from 2000 to 2008. Hazard ratios(HR) for recurrence and death were calculated. Univariate and multivariate regression analyses were conducted. C-statistics were used to compare biomarker-based to predictive models. RESULTS During a median follow-up of 12.2 years, 38 patients recurred and 87 died. The HRs for recurrence in patients with elevated AFP, AFP-L3, and DCP defined by BALAD cut-off values were 2.42(1.18-5.00), 1.86(0.98-3.52), and 2.83(1.42-5.61), respectively. For BALAD, the HRs for recurrence and death per unit increased score were 1.48(1.15-1.91) and 1.59(1.28-1.97). For BALAD-2, the HRs for recurrence and death per unit increased class were 1.45(1.06-1.98) and 1.38(1.09-1.76). For recurrence prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs. 0.64, 0.61, 0.53, and 0.53 for BALAD, BALAD-2, Milan, and UCSF, respectively. Similarly, for death prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs 0.65,0.61, 0.52, and 0.50 for BALAD, BALAD-2, Milan, and UCSF. A new model combining biomarkers with tumor size at the time of transplant(S-LAD) demonstrated the highest predictive capability with c-statistics of 0.71 and 0.69 for recurrence and death. CONCLUSION BALAD and BALAD-2 are valid in transplant HCC patients, but less predictive than the three biomarkers in combination or the three biomarkers in combination with maximal tumor diameter(S-LAD).
文摘Alzheimer＇s disease, a progressive neurodegenerative illness, is the most common torm or dementia. So far, there is neither an effective prevention nor a cure for AIzheimer＇s disease. In recent decades, stem cell therapy has been one of the most promising treatments for Alzheimer＇s disease patients. This article aims to summarize the current progress in the stem cell treatments for Alzheimer＇s disease from an experiment to a clinical research.
基金Supported by the Heart and Stroke Foundation of Canada,No.G-13-0002851the Canadian Institutes of Health Research Training Program in Regenerative Medicine to Bartczak A and Chruscinski Athe Ontario Graduate Scholarship in Science and Technology to Bartczak A
文摘AIMTo determine the effect of overexpression of fibrinogen-like protein 2 (FGL2) on regulatory T cell (Treg) and effector T (Teff) cell function on T cell-induced colitis in Rag1<sup>-/-</sup> mice.METHODSTreg and Teff cells from fgl2<sup>-/-</sup>, fgl2<sup>+/+</sup>, and fgl2<sup>Tg</sup> mice were purified by FACS. They were studied in vitro for immunosuppressive activity and cell proliferation and in vivo for their effects on the development and prevention of T cell-induced colitis in Rag1<sup>-/-</sup> mice.RESULTSIn vitro, fgl2<sup>Tg</sup> Treg had enhanced immunosuppressive activity, and fgl2<sup>Tg</sup> Teff had reduced proliferation to alloantigen stimulation. Transfer of Teff from C57Bl/6J mice (fgl2<sup>+/+</sup>) into Rag1<sup>-/-</sup> mice produced both clinical and histologic colitis with dense infiltrates of CD3<sup>+</sup> T cells, crypt abscesses and loss of goblet cells. Fgl2<sup>Tg</sup> Treg prevented the development of T cell-induced colitis, whereas fgl2<sup>+/+</sup> and fgl2<sup>-/-</sup> Treg were only partially protective. In mice that received fgl2<sup>Tg</sup> Treg, the ratio of Foxp3<sup>+</sup> to CD3<sup>+</sup> cells was increased both in the colon and in mesenteric lymph nodes, and Teff cell proliferation as determined by staining with Ki67 was reduced. Teff cells from fgl2<sup>Tg</sup> mice did not produce colitis.CONCLUSIONHere we show that fgl2<sup>Tg</sup> Teff are hypoproliferative and do not induce colitis. We further demonstrate that fgl2<sup>Tg</sup> Treg prevent colitis in contrast to fgl2<sup>+/+</sup> Treg, which were only partially protective. These studies collectively provide a rationale for exploring the use of FGL2 or Treg expressing high levels of FGL2 in the treatment of inflammatory bowel disease.
