- Browse by Author
Browsing by Author "Lin, Jingmei"
Now showing 1 - 10 of 26
Results Per Page
Sort Options
Item Adenovirus-Related Fulminant Liver Failure After Kidney Transplantation(International Scientific Information, 2022-08-06) Mihaylov, Plamen; Lutz, Andrew J.; Oppliger, Federico; Lin, Jingmei; Surgery, School of MedicineBACKGROUND: Human adenovirus is a well-known pathogen that can potentially lead to severe infection in immunocompromised patients. Adenovirus infections in solid-organ transplant recipients can range from asymptomatic to severe, prolonged, disseminated disease, and have a significant impact on morbidity, mortality, and graft survival. The clinical manifestations vary from asymptomatic and flu-like illness to severe life-threatening viremia with multi-organ failure. Post-transplant adenovirus infection is well described in kidney recipients, but in adult liver transplant recipients the impact of the virus is not well described. In this report, a case of disseminated adenovirus infection with subsequent fatal acute liver failure in a post-kidney transplant patient is presented. CASE REPORT: A 51-year-old man underwent a deceased kidney transplantation for focal segmental glomerulosclerosis. Shortly after the kidney transplantation, he received multiple plasmapheresis with additional steroid treatments for cellular rejection and reoccurrence of his primary kidney disease. Three weeks after the kidney transplant, he developed a disseminated adenovirus infection with subsequent acute liver failure. Despite the early diagnosis and aggressive treatment, the patient died. CONCLUSIONS: Patients with organ transplantation with autoimmune background etiology are usually over-immunosuppressed to avoid early rejection. In this population, opportunistic infections are not rare. Fever, general malaise, and transplant organ dysfunction are the first signs of bacterial or viral infection. Early infectious diseases work-up, including tissue biopsy, is fundamental to establish a diagnosis. Broad antibiotic and possible antiviral aggressive treatment are mandatory.Item Characterization of Chronic Gastritis in Lynch Syndrome Patients With Gastric Adenocarcinoma(Elmer Press, 2021-02) Saulino, David; Chen, Rong; Wang, Kai; Shen, Minqian; Zhang, Xuefeng; Westerhoff, Maria; Cheng, Jerome; Lin, Jingmei; Zhang, Xuchen; Feely, Michael; Liu, Xiuli; Pathology and Laboratory Medicine, School of MedicineBackground: Gastric cancer is one of the Lynch syndrome (LS)-associated malignancies. Previous studies have suggested that LS patients with gastric cancer also had chronic atrophic gastritis in the background mucosa, but further histologic characterization was not attempted. This study aims to understand the histologic features of background chronic gastritis in LS patients with gastric adenocarcinoma. Methods: Eleven LS-associated gastric cancer cases were collected from five institutions. Demographics and clinical features were retrieved by review of medical charts. Pathological material was reviewed for tumor location and histologic type. In addition, non-neoplastic gastric mucosa was assessed for inflammation (chronic and active), atrophy, intestinal metaplasia (IM) in the antrum and body, as well as pyloric gland metaplasia and enterochromaffin-like (ECL) cell hyperplasia in the body. Results: Eleven LS patients with gastric cancer (four male and seven female) with a mean age of 63 years (range: 23 - 83) were included. Ten (90.9%) had personal cancer histories; however none of the patients had family history of gastric cancer. Eight (72.7%) patients underwent gastrectomy and three had endoscopic resection. Nine (81.8%) patients had tumor in the fundus and/or body and two had tumor present in the antrum. Seven (63.6%) cases were intestinal type or mixed type carcinoma, and the remaining four were signet ring cell carcinoma. Eight (of 11, 72.7%) patients had chronic gastritis, five (45.4%) had atrophy, and four (36.3%) had intestinal metaplasia. Four of five patients with both antrum and body mucosa available for evaluation (80%), demonstrated body-predominant chronic gastritis. Four patients had germline MLH1 alterations and all of these patients had chronic gastritis, including one Helicobacter pylori (H. pylori) gastritis and three H. pylori-negative gastritis. Conclusions: None of LS patients with gastric cancer in our cohort had a family history of gastric cancer. Gastric adenocarcinomas in LS patients were primarily located in the fundus and/or body. Two-thirds of these tumors were of intestinal type and had a background chronic, H. pylori-negative gastritis. These results support a chronic atrophic gastritis with intestinal metaplasia-dysplasia-carcinoma sequence in LS-related gastric tumorigenesis, particularly in MLH1-mutated LS patients.Item Colitis as the Initial Presentation of Eosinophilic Granulomatosis with Polyangiitis(Hindawi, 2023-10-09) Menon, Sharika Gopakumar; Hugenberg, Steven; Alkashash, Ahmad M.; Lin, Jingmei; Iranmanesh, Arya M.; Medicine, School of MedicineA male patient in his early sixties with recurrent diarrhea was transferred to our hospital. The patient did not have any pulmonary or upper respiratory symptoms. He was noted to have peripheral eosinophilia. Further workup revealed a negative antineutrophilic cytoplasmic antibody titer but a positive myeloperoxidase antibody and positive proteinase 3 antibodies. A colon biopsy also revealed eosinophilic-rich granulomas in the mucosa, confirming a diagnosis of eosinophilic granulomatosis with polyangiitis. On cardiac imaging, eosinophilic myocarditis was also discovered. To treat active severe EGPA, the patient received high-dose corticosteroids and intravenous cyclophosphamide. The occurrence of gastrointestinal involvement as an initial manifestation of eosinophilic granulomatosis with polyangiitis is infrequent, emphasizing the significance of its recognition. This case underscores the importance of identifying and diagnosing such atypical presentations to facilitate timely and appropriate management.Item Comparison of Artificial Intelligence and Eyeball Method in the Detection of Fatty Liver Disease(2023-07-26) Catron, Evan J.; Passarelli, Robert P.; Danielle, Wilmes; Wei, Barry; Le, Thi M.U.; Li, Ping; Zhang, Wenjun; Lin, Jingmei; Melcher, Mark L.; Mihaylov, Plamen V.; Kubal, Chandrashekhar A.; Mangus, Robert S.; Ekser, BurcinBackground: Quantification of liver fat content relies on visual microscopic inspection of liver biopsies by pathologists. Their percent macrosteatosis (%MaS) estimation is vital in determining donor liver transplantability; however, the eyeball method may vary between observers. Overestimations of %MaS can potentially lead to the discard of viable donor livers. We hypothesize that artificial intelligence (AI) could be helpful in providing a more objective and accurate measurement of %MaS. Methods: Literature review identified HALO (image analysis) and U-Net (deep-learning) as high-accuracy AI programs capable of calculating %MaS in liver biopsies. We compared (i) an experienced pathologist’s and (ii) a transplant surgeon’s eyeball %MaS estimations from de-novo liver transplant (LT) biopsy samples taken 2h post-reperfusion to (iii) the HALO-calculated %MaS (Fig.1). 250 patients had undergone LT at Indiana University between 2020-2021, and 211 had sufficient data for inclusion. Each biopsy was digitized into 5 random non-overlapping tiles at 20x magnification (a total of 1,055 images). We used HALO software for analysis and set the minimum vacuole area to 10μm² to avoid the inclusion of microsteatosis. Microsteatosis was excluded by the pathologist and the surgeon by the eyeball method using the same 1,055 images. Each %MaS estimation was compared with early allograft dysfunction (EAD). EAD is defined by the presence of at least one of the following: INR >1.6 on postoperative day (POD) 7, total bilirubin >10mg/dL on POD7, or AST/ALT >2000IU/L within the first 7 days following LT. Results: Of 211 LTs, 42 (19.9%) had EAD. The mean %MaS estimation of pathologist and transplant surgeon were 6.3% (SD: 11.9%) and 3.2% (SD: 6.4%), respectively. HALO yielded a significantly lower mean %MaS of 2.6% (SD: 2.6%) than the pathologist’s eyeball method (p<0.001). The mean %MaS calculated by HALO was higher in EAD patients than in non-EAD (p=0.032), but this difference did not reach statistical significance in the pathologist’s estimation (p=0.069). Conclusions: Although mean %MaS measurements from all parties were mild (<10%), human eyeball estimations of %MaS were significantly higher than HALO’s %MaS. The HALO-calculated %MaS differed significantly between the EAD and non-EAD LTs which might suggest a possible correlation between the AI’s steatosis analysis and EAD outcomes. However, pathologic variables other than %MaS (necrosis or cholestasis) should be included in future analyses to determine whether %MaS is the dominant parameter predicting EAD. AI is a promising tool to quantify liver steatosis and will help pathologists and transplant surgeons predict liver transplant viability.Item Comparison of EUS-guided tissue acquisition using two different 19-gauge core biopsy needles: a multicenter, prospective, randomized, and blinded study(Thieme Publishing Group, 2015-10) DeWitt, John; Cho, Chang-Min; Lin, Jingmei; Al-Haddad, Mohammad; Canto, Marcia Irene; Salamone, Ashley; Hruban, Ralph H.; Messallam, Ahmed A.; Khashab, Mouen A.; Department of Medicine, IU School of MedicineBACKGROUND AND STUDY AIMS: The optimal core biopsy needle for endoscopic ultrasound (EUS) is unknown. The principle aim of this study is to compare outcomes of EUS-fine-needle biopsy (EUS-FNB) with a new 19-gauge EUS histology needle (ProCore, Cook Medical Inc., Winston-Salem, North Carolina, United States) to a conventional 19-gauge Tru-Cut biopsy (EUS-TCB) needle (19G, Quick-Core, Cook Medical Inc.). PATIENTS AND METHODS: Patients referred for EUS who require possible histologic biopsy were prospectively randomized to EUS-FNB or EUS-TCB. With the initial needle, ≤ 3 biopsies were obtained until either technical failure or an adequate core was obtained. Patients with suspected inadequate biopsies were crossed over to the other needle and similarly ≤ 3 passes were obtained until adequate cores or technical failure occurred. Technical success, diagnostic histology, accuracy and complication rates were evaluated. RESULTS: Eighty-five patients (mean 58 years; 43 male) were randomized to FNB (n = 44) and TCB (n = 41) with seven patients excluded. Procedure indication, biopsy site, mass size, number of passes, puncture site, overall technical success and adverse events were similar between the two groups. FNB specimens had a higher prevalence of diagnostic histology (85 % vs. 57 %; P = 0.006), accuracy (88 % vs. 62 %; P = 0.02), mean total length (19.4 vs. 4.3 mm; P = 0.001), mean complete portal triads from liver biopsies (10.4 vs. 1.3; P = 0.0004) and required fewer crossover biopsies compared to those of TCB (2 % vs. 65 %; P = 0.0001). Overall technical success and complication rates were comparable. CONCLUSION: EUS-FNB using a 19-gauge FNB needle is superior to 19-gauge EUS-TCB needle.Item Hepatic Autophagy Deficiency Compromises FXR Functionality and Causes Cholestatic Injury(AASLD, 2019) Khambu, Bilon; Li, Tiangang; Yan, Shengmin; Yu, Changshun; Chen, Xiaoyun; Goheen, Michael; Li, Yong; Lin, Jingmei; Cummings, Oscar W.; Lee, Youngmin A.; Friedman, Scott; Dong, Zheng; Feng, Gen-Sheng; Wu, Shangwei; Yin, Xiao-Ming; Pathology and Laboratory Medicine, School of MedicineAutophagy is important for hepatic homeostasis, nutrient regeneration and organelle quality control. We investigated the mechanisms by which liver injury occurred in the absence of autophagy function. We found that mice deficient in autophagy due to the lack of Atg7 or Atg5, key autophagy‐related genes, manifested intracellular cholestasis with increased levels of serum bile acids, a higher ratio of TMCA/TCA in the bile, increased hepatic bile acid load, abnormal bile canaliculi and altered expression of hepatic transporters. In determining the underlying mechanism, we found that autophagy sustained and promoted the basal and upregulated expression of Fxr in the fed and starved conditions, respectively. Consequently, expression of Fxr and its downstream genes, particularly Bsep, and the binding of FXR to the promoter regions of these genes, were suppressed in autophagy‐deficient livers. In addition, co‐deletion of Nrf2 in autophagy deficiency status reversed the FXR suppression. Furthermore, the cholestatic injury of autophagy‐deficient livers was reversed by enhancement of FXR activity or expression, or by Nrf2 deletion.Item In a pilot study, reduced fatty acid desaturase 1 function was associated with nonalcoholic fatty liver disease and response to treatment in children(Springer Nature, 2018-11) Nobili, Valerio; Alisi, Anna; Liu, Zhipeng; Liang, Tiebing; Crudele, Annalisa; Raponi, Massimiliano; Lin, Jingmei; Chalasani, Naga P.; Liu, Wanqing; Pathology and Laboratory Medicine, School of MedicineBACKGROUND: FADS1 gene encodes delta 5 desaturase, a rate-limiting enzyme in the metabolism of n-3 and n-6 polyunsaturated fatty acids (PUFAs). Minor alleles of FADS1 locus polymorphisms are associated with reduced FADS1 expression and intra-hepatic fat accumulation. However, the relationship between FADS1 expression and pediatric nonalcoholic fatty liver disease (NAFLD) risk remains to be explored. METHODS: We analyzed FADS1 transcription levels and their association with intra-hepatic fat and histology in children, and we performed pathway enrichment analysis on transcriptomic profiles associated with FADS1 polymorphisms. We also evaluated the weight of FADS1 alleles on the response to combined docosahexaenoic acid, choline, and vitamin E (DHA-CHO-VE) treatment. RESULTS: FADS1 mRNA level was significantly and inversely associated with intra-hepatic fat (p = 0.004), degree of steatosis (p = 0.03), fibrosis (p = 0.05), and NASH (p = 0.008) among pediatric livers. Transcriptomics demonstrated a significant enrichment of a number of pathways strongly related to NAFLD (e.g., liver damage, fibrosis, and hepatic stellate cell activation). Compared to children who are common allele homozygotes, children with FADS1 minor alleles had a greater reduction in steatosis, fibrosis, and NAFLD activity score after DHA-CHO-VE. CONCLUSION: This study suggests that decreased FADS1 expression may be associated with NAFLD in children but an increased response to DHA-CHO-VE.Item Integrated miR-mRNA Network Underlying Hepatic Fat Accumulation in HumansSrivastava, Rajneesh; Wang, Xiaoliang; Lin, Jingmei; Wei, Rongrong; Chaturvedi, Praneet; Chalasani, Naga P.; Janga, Sarath Chandra; Liu, WanqingBackground: An integrate miRs and mRNAs analysis in the development of Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH) is lacking. We aimed to identify miRs as well as the miR-mRNA regulatory network involved in hepatic fat accumulation and human NAFLD. Materials and Methods: Hepatic fat content (HFC) was measured, and liver histology was characterized for 73 liver tissue samples. MicroRNAs and mRNAs significantly associated with HFC were identified based on genome-wide mRNA and miR expression profiling data. These miRs and mRNAs were further used to build miR-mRNA association networks in NAFLD and normal samples based on the potential miR-mRNA targeting, as well as to conduct a pathway enrichment analysis. Results: We identified 62 miRs significantly correlated with HFC (p<0.05), with miR-518b and miR-19b demonstrated to be the most significant positive and negative correlation with HFC, respectively (p<0.008 for both). Many miRs that were previously associated with NAFLD/NASH were also observed. Integrated network analysis indicated that a few miRs-30b*, 616, 17*, 129-5p, 204, and 20a controlled >80% of HFC-associated mRNAs in this network, and the regulation network was significantly rewired from normal to NAFLD. Pathway analyses revealed that inflammation pathways mediated by chemokine and cytokine signaling, Wnt signaling, lntegrin signaling and Natural killer cell mediated cytotoxicity were enriched (p<0.05) in hepatic fat accumulation.Item Integrative omics analysis identifies macrophage migration inhibitory factor signaling pathways underlying human hepatic fibrogenesis and fibrosis(Wolters Kluwer, 2019-03-01) Liu, Zhipeng; Chalasani, Naga; Lin, Jingmei; Gawrieh, Samer; He, Yuan; Tseng, Yan J.; Liu, Wanqing; Medicine, School of MedicineThe genetic basis underlying liver fibrosis remains largely unknown. We conducted a study to identify genetic alleles and underlying pathways associated with hepatic fibrogenesis and fibrosis at the genome-wide level in 121 human livers. By accepting a liberal significance level of P<1e-4, we identified 73 and 71 candidate loci respectively affecting the variability in alpha-smooth muscle actin (α-SMA) levels (fibrogenesis) and total collagen content (fibrosis). The top genetic loci associated with the two markers were BAZA1 and NOL10 for α-SMA expression and FAM46A for total collagen content (P<1e-6). We further investigated the relationship between the candidate loci and the nearby gene transcription levels (cis-expression quantitative trait loci) in the same liver samples. We found that 44 candidate loci for α-SMA expression and 44 for total collagen content were also associated with the transcription of the nearby genes (P<0.05). Pathway analyses of these genes indicated that macrophage migration inhibitory factor (MIF) related pathway is significantly associated with fibrogenesis and fibrosis, though different genes were enriched for each marker. The association between the single nucleotide polymorphisms, MIF and α-SMA showed that decreased MIF expression is correlated with increased α-SMA expression, suggesting that variations in MIF locus might affect the susceptibility of fibrogenesis through controlling MIF gene expression. In summary, our study identified candidate alleles and pathways underlying both fibrogenesis and fibrosis in human livers. Our bioinformatics analyses suggested MIF pathway as a strong candidate involved in liver fibrosis, thus further investigation for the role of the MIF pathway in liver fibrosis is warranted. The study was reviewed and approved by the Institutional Review Board (IRB) of Wayne State University (approval No. 201842) on May 17, 2018.Item Interobserver study on histologic features of idiopathic non-cirrhotic portal hypertension(BMC, 2020-10-23) Kmeid, Michel; Zuo, Chunlai; Lagana, Stephen M.; Choi, Won-Tak; Lin, Jingmei; Yang, Zhaohai; Liu, Xiuli; Westerhoff, Maria; Fiel, M. Isabel; Affolter, Kajsa; Choi, Eun-Young K.; Lee, Hwajeong; Pathology and Laboratory Medicine, School of MedicineBackground Histologic features of idiopathic non-cirrhotic portal hypertension (INCPH) may overlap with those without INCPH. Recently, these features have been recognized as part of the larger spectrum of porto-sinusoidal vascular disease (PSVD). We assessed interobserver agreement on histologic features that are commonly associated with INCPH and studied whether a provision of relevant clinical history improves interobserver agreement. Methods The examined histologic features include lobular (such as anisocytosis, nodular regeneration, sinusoidal dilatation, increased parenchymal draining veins, and incomplete fibrous septa) and portal tract changes (such as paraportal shunting vessel(s), portal tract remnant, increased number of portal vessels, and obliterative portal venopathy). Thirty-four archived liver samples from patients with (group A) and without (group B) INCPH were retrieved. A total of 90 representative images of lobules (L) and portal tracts (P) were distributed among 9 liver pathologists blinded to true clinical history. Each pathologist answered multiple choice questions based on the absence (Q1) or presence (Q2) of clinical history of portal hypertension. Fleiss’ kappa coefficient analysis (unweighted) was performed to assess interobserver agreement on normal versus abnormal diagnosis, in L and P, based on Q1 and Q2. Results The kappa values regarding normal versus abnormal diagnosis were 0.24, 0.24, 0.18 and 0.18 for L-Q1, L-Q2, P-Q1, and P-Q2, respectively. With true clinical history provided, the kappa values were L- 0.32, P-0.17 for group A and L-0.12, P-0.14 for group B. Four pathologists changed their assessments based on the provided history. Interobserver agreement on the interpretation of L and P as normal versus abnormal was slight to fair regardless of provision of clinical history. Conclusions Our findings indicate that the histologic features of INCPH/PSVD are not limited to patients with portal hypertension and are subject to significant interobserver variation. Supplementary information The online version contains supplementary material available at 10.1186/s13000-020-01049-0.
- «
- 1 (current)
- 2
- 3
- »