Browsing by Author "Li, Liang"
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Item Association of Chronic Pancreatitis Pain Features With Physical, Mental, and Social Health(Elsevier, 2023) Yadav, Dhiraj; Askew, Robert L.; Palermo, Tonya; Li, Liang; Andersen, Dana K.; Chen, Minxing; Fisher, William E.; Fogel, Evan L.; Forsmark, Christopher E.; Hart, Phil A.; Othman, Mohamed O.; Pandol, Stephen J.; Park, Walter G.; Topazian, Mark D.; Van Den Eeden, Stephen K.; Swaroop Vege, Santhi; Yang, Yunlong; Serrano, Jose; Conwell, Darwin L.; Consortium for the Study of Chronic Pancreatitis; Diabetes, and Pancreatic Cancer (CPDPC); Medicine, School of MedicineBackground and aims: Pain is a cardinal symptom of chronic pancreatitis (CP). Using Patient-Reported Outcomes Measurement Information System (PROMIS) measures, we characterized physical and mental health and symptom profiles of a well-defined cohort of individuals with CP and compared them with control subjects. Among patients with CP, we also examined associations between pain (intensity, temporal nature) and PROMIS symptom profiles and the prevalence of clinically significant psychological comorbidities. Methods: We analyzed baseline data in 488 CP patients and 254 control subjects enrolled in PROCEED (Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies), an ongoing longitudinal cohort study. Participants completed the PROMIS-Global Health, which captures global physical and mental health, and the PROMIS-29 profile, which captures 7 symptom domains. Self-reported pain was categorized by severity (none, mild-moderate, severe) and temporal nature (none, intermittent, constant). Demographic and clinical data were obtained from the PROCEED database. Results: Pain was significantly associated with impairments in physical and mental health. Compared with participants with no pain, CP participants with severe pain (but not mild-moderate pain) had more decrements in each PROMIS domain in multivariable models (effect sizes, 2.54-7.03) and had a higher prevalence of clinically significant depression, anxiety, sleep disturbance, and physical disability (odds ratios, 2.11-4.74). Similar results were noted for constant pain (but not intermittent pain) for PROMIS domains (effect sizes, 4.08-10.37) and clinically significant depression, anxiety, sleep disturbance and physical disability (odds ratios, 2.80-5.38). Conclusions: Severe and constant pain are major drivers for poor psychological and physical health in CP. Systematic evaluation and management of psychiatric comorbidities and sleep disturbance should be incorporated into routine management of patients with CP.Item Association of Pancreatic Steatosis With Chronic Pancreatitis, Obesity, and Type 2 Diabetes Mellitus(Lippincott, Williams & Wilkins, 2019-03) Tirkes, Temel; Jeon, Christie Y.; Li, Liang; Joon, Aron Y.; Seltman, Ted A.; Sankar, Meghana; Persohn, Scott A.; Territo, Paul R.; Radiology and Imaging Sciences, School of MedicineObjective: The aim of this study was to determine the association of the pancreatic steatosis with obesity, chronic pancreatitis (CP), and type 2 diabetes mellitus. Methods: Patients (n = 118) were retrospectively identified and categorized into no CP (n = 60), mild (n = 21), moderate (n = 27), and severe CP (n = 10) groups based on clinical history and magnetic resonance cholangiopancreatography using the Cambridge classification as the diagnostic standard. Visceral and subcutaneous compartments were manually segmented, and fat tissue was quantitatively measured on axial magnetic resonance imaging. Results: Pancreatic fat fraction showed a direct correlation with fat within the visceral compartment (r = 0.54). Patients with CP showed higher visceral fat (P = 0.01) and pancreatic fat fraction (P < 0.001): mild, 24%; moderate, 23%; severe CP, 21%; no CP group, 15%. Patients with type 2 diabetes mellitus showed higher pancreatic steatosis (P = 0.03) and higher visceral (P = 0.007) and subcutaneous fat (P = 0.004). Interobserver variability of measuring fat by magnetic resonance imaging was excellent (r ≥ 0.90–0.99). Conclusions: Increased visceral adipose tissue has a moderate direct correlation with pancreatic fat fraction. Chronic pancreatitis is associated with higher pancreatic fat fraction and visceral fat. Type 2 diabetes mellitus is associated with higher pancreatic fat fraction and visceral and subcutaneous adiposity.Item A case of squamous cell lung cancer presented as a cystic lesion and recurrent pneumothoraces(Elsevier, 2021-03-09) Aldaghlawi, Fadi; Von Holzen, Urs; Li, Liang; Hadid, Walid; Medicine, School of MedicineWe report a rare case of a 70-year-old male with recurrent pneumothoraces within one year treated with intermittent insertion of chest tube on each occasion. Diagnostic testing was notable for a cystic lesion in the left lung that was initially interpreted as bulla on chest x-ray and chest computed tomographic scan. Due to thickening and nodularity changes of the thin wall of the cystic lesion, the patient underwent left upper lobectomy. Pathology showed poorly differentiated squamous cell carcinoma of the cystic lesion wall. This case emphasizes the importance of monitoring pulmonary cystic lesions especially in patients with a history of smoking and emphysema.Item Characterizing mechanism-based pain phenotypes in patients with chronic pancreatitis: a cross-sectional analysis of the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies(Wolters Kluwer, 2023) Saloman, Jami L.; Conwell, Darwin L.; Fogel, Evan; Vege, Santhi Swaroop; Li, Liang; Li, Shuang; Andersen, Dana K.; Fisher, William E.; Forsmark, Christopher E.; Hart, Phil A.; Pandol, Stephen J.; Park, Walter G.; Evans Phillips, Anna; Topazian, Mark; Van Den Eeden, Stephen K.; Serrano, Jose; Yadav, Dhiraj; Consortium for the Study of Chronic Pancreatitis, Diabetes and Pancreatic Cancer; Medicine, School of MedicinePain is common in chronic pancreatitis (CP) and profoundly reduces quality of life (QoL). Multiple underlying mechanisms contribute to a heterogenous pain experience and reduce efficacy of pain management. This study was designed to characterize the distribution of mechanism-based pain phenotypes in painful CP. The data analyzed were collected as part of the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies, an NCI/NIDDK-funded longitudinal study of the natural history of CP. The PROspective Evaluation of Chronic pancreatitis for EpidEmiologic and translational stuDies includes patient-reported outcome (PRO) measures of pain, medication use, global health, and QoL. Of subjects (N = 681) with CP, 80% experienced abdominal pain within the year before enrollment. Subjects who experienced pain in the week before enrollment (N = 391) completed PROMIS Neuropathic and Nociceptive Pain Quality instruments which were then used to classify them by pain type: 40% had nociceptive, 5% had neuropathic-like, and 32% had both types of pain. The prevalence of having both types of pain was higher among women and subjects with diabetes mellitus, whereas nociceptive-only pain was more prevalent among men and those with pancreatic duct stricture. Other factors, including pain medication use and healthcare utilization, did not differ between groups based on pain type. Subjects in the Both group had significantly worse health and QoL scores relative to those with nociceptive-only pain, suggesting that using psychosocial pain surveys may be useful for understanding pain subtypes in patients with CP. Additional research is needed to identify biochemical and biophysical signatures that may associate with and predict responses to mechanism-specific interventions.Item Diagnosis of chronic pancreatitis using semi-quantitative MRI features of the pancreatic parenchyma: results from the multi-institutional MINIMAP study Temel Tirkes1,18, Dhiraj Yadav2(Springer, 2023) Tirkes, Temel; Yadav, Dhiraj; Conwell, Darwin L.; Territo, Paul R.; Zhao, Xuandong; Persohn, Scott A.; Dasyam, Anil K.; Shah, Zarine K.; Venkatesh, Sudhakar K.; Takahashi, Naoki; Wachsman, Ashley; Li, Liang; Li, Yan; Pandol, Stephen J.; Park, Walter G.; Swaroop Vege, Santhi; Hart, Phil A.; Topazian, Mark; Andersen, Dana K.; Fogel, Evan L.; Consortium for the Study of Chronic Pancreatitis, Diabetes, Pancreatic Cancer (CPDPC); Radiology and Imaging Sciences, School of MedicinePurpose: To determine the diagnostic performance of parenchymal MRI features differentiating CP from controls. Methods: This prospective study performed abdominal MRI scans at seven institutions, using 1.5 T Siemens and GE scanners, in 50 control and 51 definite CP participants, from February 2019 to May 2021. MRI parameters included the T1-weighted signal intensity ratio of the pancreas (T1 score), arterial-to-venous enhancement ratio (AVR) during venous and delayed phases, pancreas volume, and diameter. We evaluated the diagnostic performance of these parameters individually and two semi-quantitative MRI scores derived using logistic regression: SQ-MRI Model A (T1 score, AVR venous, and tail diameter) and Model B (T1 score, AVR venous, and volume). Results: When compared to controls, CP participants showed a significantly lower mean T1 score (1.11 vs. 1.29), AVR venous (0.86 vs. 1.45), AVR delayed (1.07 vs. 1.57), volume (54.97 vs. 80.00 ml), and diameter of the head (2.05 vs. 2.39 cm), body (2.25 vs. 2.58 cm), and tail (1.98 vs. 2.51 cm) (p < 0.05 for all). AUCs for these individual MR parameters ranged from 0.66 to 0.79, while AUCs for the SQ-MRI scores were 0.82 and 0.81 for Model A (T1 score, AVR venous, and tail diameter) and Model B (T1 score, AVR venous, and volume), respectively. After propensity-matching adjustments for covariates, AUCs for Models A and B of the SQ-MRI scores increased to 0.92 and 0.93, respectively. Conclusion: Semi-quantitative parameters of the pancreatic parenchyma, including T1 score, enhancement ratio, pancreas volume, diameter and multi-parametric models combining these parameters are helpful in diagnosis of CP. Longitudinal analyses including more extensive population are warranted to develop new diagnostic criteria for CP.Item Distinct serum immune profiles define the spectrum of acute and chronic pancreatitis from the multi-center PROCEED study(AGA, 2023-07) Lee, Bomi; Jones, Elaina K.; Manohar, Murli; Li, Liang; Yadav, Dhiraj; Conwell, Darwin L.; Hart, Phil A.; Vege, Santhi Swaroop; Fogel, Evan L.; Serrano, Jose; Anderson, Dana; Bellin, Melena D.; Topazian, Mark D.; Van Den Eeden, Stephen K.; Pandol, Stephen J.; Forsmark, Chris E.; Fisher, William E.; Park, Walter G.; Husain, Sohail Z.; Habtezion, Aida; Medicine, School of MedicineBackground & Aims Pancreatitis is a disease continuum, starting with acute pancreatitis (AP) and progressing in some cases to recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP). Currently, there are no approved therapies or early diagnostic or prognostic biomarkers for pancreatitis. The current study examined whether patient serum immune profiling could identify noninvasive biomarkers and provide mechanistic insight into the disease continuum of pancreatitis. Methods Using Olink immunoassay, we assessed the protein levels of 92 immune markers in serum samples from participants enrolled in the Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED) study of the Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) consortium. Samples (N = 231) were obtained from individuals without pancreatic disease (n = 56) and from those with chronic abdominal pain (CAP) (n = 24), AP (n = 38), RAP (n = 56), and CP (n = 57). Results A total of 33 immune markers differentiated the combined pancreatitis groups from controls. Immune markers related to interleukin (IL) 17 signaling distinguished CP from AP and RAP. Similarly, the serum level of IL17A and C-C motif chemokine ligand 20 differentiated CP from CAP, suggesting the involvement of T helper 17 cells in CP pathogenesis. The receiver operator characteristic curve with 2 immune markers (IL17A and sulfotransferase 1A1) could differentiate CP from CAP (optimistic area under the curve = 0.78). The macrophage classical activation pathway elevated along the continuum of pancreatitis, suggesting an accumulation of proinflammatory signals over disease progression. Several immune markers were associated with smoking, alcohol, and diabetes status. Conclusions Immune profiling of serum samples from a large pancreatitis cohort led to identifying distinct immune markers that could serve as potential biomarkers to differentiate the varying pancreatitis disease states. In addition, the finding of IL17 signaling in CP could provide insight into the immune mechanisms underlying disease progression.Item Evaluation of variable flip angle, MOLLI, SASHA, and IR-SNAPSHOT pulse sequences for T1 relaxometry and extracellular volume imaging of the pancreas and liver(Elsevier, 2019-06-04) Tirkes, Temel; Zhao, Xuandong; Lin, Chen; Stuckey, Alex Jordan; Li, Liang; Giri, Shivriman; Nickel, Dominik; Radiology and Imaging Sciences, School of MedicinePurpose Compare four T1 mapping pulse sequences for T1 relaxometry and extracellular volume (ECV) fraction of the pancreas and liver Materials and Methods In vitro phase of this prospective study was performed on a T1 phantom, followed by imaging twenty-two patients. Variable flip angle (VFA), modified Look-Locker inversion recovery (MOLLI), prototype saturation recovery single-shot acquisition (SASHA), and prototype inversion recovery (IR-SNAPSHOT) pulse sequences were used to obtain T1 and ECV maps on the same 1.5T MR scanner using the same imaging protocol. Results In vitro tests showed almost perfect precision of MOLLI (ρc=0.9998), SASHA (ρc=0.9985) and IR-SNAPSHOT (ρc=0.9976) while VFA showed relatively less, however substantial precision (ρc=0.9862). Results of patient scans showed similar ECV fraction of the liver (p=0.08), pancreas (p=0.43), and T1 of the liver (p=0.08) with all pulse sequences. T1 of the pancreas with MOLLI, SASHA and IR-SNAPSHOT were statistically similar (p>0.05). Conclusion MOLLI, SASHA and IR-SNAPSHOT provided almost perfect in vitro precision and similar T1 during in vivo scans. Similar ECV fractions of the liver and pancreas were obtained with all sequences. More refinement of pulse sequences to provide sufficient spatial coverage in one breath hold together with high precision would be desirable in abdominal imaging.Item High Prevalence of Osteopathy in Chronic Pancreatitis: A Cross-sectional Analysis From the PROCEED Study(Elsevier, 2022) Hart, Phil A.; Yadav, Dhiraj; Li, Liang; Appana, Savi; Fisher, William; Fogel, Evan; Forsmark, Chris E.; Park, Walter G.; Pandol, Stephen; Topazian, Mark D.; Van Den Eden, Stephen K.; Vege, Santhi Swaroop; Bradley, David; Serrano, Jose; Conwell, Darwin L.; Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC); Medicine, School of MedicineBackground & aims: Chronic pancreatitis (CP) is associated with osteopathy (osteoporosis or osteopenia). However, existing literature is mostly limited to retrospective or administrative studies that have not clearly defined the prevalence and risk factors. Our aim was to identify patient- and disease-related associations with osteopathy in a prospective cohort study of CP. Methods: We studied 282 subjects with definitive CP enrolled in the PROCEED study who had a baseline dual-energy X-ray absorptiometry (DXA) scan. Osteopenia and osteoporosis were defined using the lowest T-scores. Clinical data were collected using standardized case report forms. Comparisons were performed with a multivariate logistic regression model with forward selection to identify risk factors for osteopathy. Results: The majority of subjects had osteopathy on DXA scan (56.0%; 17.0% osteoporosis; 39.0% osteopenia). Subjects with osteopathy had a higher prevalence of traumatic (40.0% vs 26.4%; P = .02) and spontaneous fractures (3.9% vs 0; P = .04). On multivariate analysis, older age (odds ratio [OR], 1.29 per 5 years; 95% confidence interval [CI], 1.15-1.45), female sex (OR, 3.08; 95% CI, 1.75-5.43), white race (OR, 2.68; 95% CI, 1.20-6.01), and underweight body mass index category (OR, 7.40; 95% CI, 1.56-34.99) were associated with higher probability of osteopathy. There were no significant associations between osteopathy and other patient and disease-related features of CP. Conclusion: In the largest study of patients with CP who underwent DXA screening, the majority had osteopathy. There are overlapping risk factors with osteopathy in the general population, but the high prevalence in men and younger women supports the need for future investigations into the mechanisms of bone loss in CP.Item Inter-observer variability of radiologists for Cambridge classification of chronic pancreatitis using CT and MRCP: results from a large multi-center study(SpringerLink, 2020-05) Tirkes, Temel; Shah, Zarine K.; Takahashi, Naoki; Grajo, Joseph R.; Chang, Stephanie T.; Wachsman, Ashley M.; Mawad, Kareem; Farinas, Carlos A.; Li, Liang; Appana, Savitri N.; Conwell, Darwin L.; Yadav, Dhiraj; Dasyam, Anil K.; Radiology and Imaging Sciences, School of MedicinePurpose: Determine inter-observer variability among radiologists in assigning Cambridge Classification (CC) of chronic pancreatitis (CP) based on magnetic resonance imaging (MRI)/magnetic resonance cholangiopancreatography (MRCP) and contrast-enhanced CT (CECT). Methods: Among 422 eligible subjects enrolled into the PROCEED study between 6/2017 and 8/2018, 39 were selected randomly for this study (chronic abdominal pain (n = 8; CC of 0), suspected CP (n = 22; CC of 0, 1 or 2) or definite CP (n = 9; CC of 3 or 4). Each imaging was scored by the local radiologist (LRs) and three of five central radiologists (CRs) at other consortium sites. The CRs were blinded to clinical data and site information of the participants. We compared the CC score assigned by the LR with the consensus CC score assigned by the CRs. The weighted kappa statistic (K) was used to estimate the inter-observer agreement. Results: For the majority of subjects (34/39), the group assignment by LR agreed with the consensus composite CT/MRCP score by the CRs (concordance ranging from 75 to 89% depending on cohort group). There was moderate agreement (63% and 67% agreed, respectively) between CRs and LRs in both the CT score (weighted Kappa [95% CI] = 0.56 [0.34, 0.78]; p-value = 0.57) and the MR score (weighted Kappa [95% CI] = 0.68 [0.49, 0.86]; p-value = 0.72). The composite CT/MR score showed moderate agreement (weighted Kappa [95% CI] = 0.62 [0.43, 0.81]; p-value = 0.80). Conclusion: There is a high degree of concordance among radiologists for assignment of CC using MRI and CT.Item Magnetic resonance imaging as a non-invasive method for the assessment of pancreatic fibrosis (MINIMAP): a comprehensive study design from the consortium for the study of chronic pancreatitis, diabetes, and pancreatic cancer(Springer, 2019-05-14) Tirkes, Temel; Yadav, Dhiraj; Conwell, Darwin L.; Territo, Paul R.; Zhao, Xuandong; Venkatesh, Sudhakar K.; Kolipaka, Arunark; Li, Liang; Pisegna, Joseph R.; Pandol, Stephen J.; Park, Walter G.; Topazian, Mark; Serrano, Jose; Fogel, Evan L.; Radiology and Imaging Sciences, School of MedicineCharacteristic features of chronic pancreatitis (CP) may be absent on standard imaging studies. Quantitative Magnetic Resonance Imaging (MRI) techniques such as T1 mapping, extracellular volume (ECV) fraction, diffusion-weighted imaging (DWI) with apparent diffusion coefficient map (ADC), MR elastography (MRE), and T1-weighted signal intensity ratio (SIR) have shown promise for the diagnosis and grading severity of CP. However, radiologists still use the Cambridge classification which is based on traditional ductal imaging alone. There is an urgent need to develop new diagnostic criteria that incorporate both parenchymal and ductal features of CP seen by MRI/MRCP. Designed to fulfill this clinical need, we present the MINIMAP study, which was funded in September 2018 by the National Institutes of Health. This is a comprehensive quantitative MR imaging study which will be performed at multiple institutions in well-phenotyped CP patient cohorts. We hypothesize that quantitative MRI/MRCP features can serve as valuable non-invasive imaging biomarkers to detect and grade CP. We will evaluate the role of T1 relaxometry, ECV, T1-weighted gradient echo SIR, MRE, arteriovenous enhancement ratio, ADC, pancreas volume/atrophy, pancreatic fat fraction, ductal features, and pancreatic exocrine output following secretin stimulation in the assessment of CP. We will attempt to generate a multi-parametric pancreatic tissue fibrosis (PTF) scoring system. We anticipate that a quantitative scoring system may serve as a biomarker of pancreatic fibrosis; hence this imaging technique can be used in clinical practice as well as clinical trials to evaluate the efficacy of agents which may slow the progression or reverse measures of CP.