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1.
Artículo en Inglés | MEDLINE | ID: mdl-38713142

RESUMEN

BACKGROUND: Cyclic vomiting syndrome (CVS) is a disorder of gut brain interaction (DGBI) often triggered by stress. Interventions like meditation may improve psychological outcomes and Health-Related Quality of Life (HRQoL), but their efficacy and the underlying mechanism are unknown. METHODS: We conducted a 6-week single-arm pilot study to assess the effects of Heartfulness meditation (HFM) in CVS using a custom-designed meditation app. Primary outcomes included state and trait anxiety and mood state changes pre- vs. post-meditation, and secondary outcomes were psychological distress, coping, sleep quality and HRQoL at baseline and weeks 3 and 6. Serum concentrations of endocannabinoids N-arachidonylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG) and related lipids were measured pre-and-post HFM at baseline and week 6. RESULTS: In 30 treatment completers, there was a significant improvement in state anxiety (p<0.001), total mood disturbance (p<0.001), and other mood states (all p values <0.05) across the three time points. Trait anxiety was also improved at week 6. There was a significant improvement in psychological distress (global severity index), sleep quality (daytime dysfunction), coping (using religion/spirituality) and HRQoL (mental and physical) across the three time points (all p <0.05). Significant increases in AEA and related lipids N-oleoylethanolamine and palmitoylethanolamide post-vs.-pre HFM were observed at week 6 (p<0.001, 0.002, 0.003, respectively). No adverse effects were noted. DISCUSSION: App-delivered HFM is feasible, safe and effective and improves psychological outcomes and augments endocannabinoids. This provides insight into the mechanism underlying HFM and has potential for widespread use as a digital therapeutic in CVS and other DGBI.Study Highlights.

2.
Cancer Immunol Immunother ; 73(6): 96, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38619621

RESUMEN

Pancreatic cancer is an aggressive disease with a 5 year survival rate of 13%. This poor survival is attributed, in part, to limited and ineffective treatments for patients with metastatic disease, highlighting a need to identify molecular drivers of pancreatic cancer to target for more effective treatment. CD200 is a glycoprotein that interacts with the receptor CD200R and elicits an immunosuppressive response. Overexpression of CD200 has been associated with differential outcomes, depending on the tumor type. In the context of pancreatic cancer, we have previously reported that CD200 is expressed in the pancreatic tumor microenvironment (TME), and that targeting CD200 in murine tumor models reduces tumor burden. We hypothesized that CD200 is overexpressed on tumor and stromal populations in the pancreatic TME and that circulating levels of soluble CD200 (sCD200) have prognostic value for overall survival. We discovered that CD200 was overexpressed on immune, stromal, and tumor populations in the pancreatic TME. Particularly, single-cell RNA-sequencing indicated that CD200 was upregulated on inflammatory cancer-associated fibroblasts. Cytometry by time of flight analysis of PBMCs indicated that CD200 was overexpressed on innate immune populations, including monocytes, dendritic cells, and monocytic myeloid-derived suppressor cells. High sCD200 levels in plasma correlated with significantly worse overall and progression-free survival. Additionally, sCD200 correlated with the ratio of circulating matrix metalloproteinase (MMP) 3: tissue inhibitor of metalloproteinase (TIMP) 3 and MMP11/TIMP3. This study highlights the importance of CD200 expression in pancreatic cancer and provides the rationale for designing novel therapeutic strategies that target this protein.


Asunto(s)
Fibroblastos Asociados al Cáncer , Neoplasias Pancreáticas , Humanos , Inmunosupresores , Páncreas , Microambiente Tumoral
3.
Diagn Progn Res ; 8(1): 6, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38561864

RESUMEN

Acute pancreatitis (AP) is an acute inflammatory disorder that is common, costly, and is increasing in incidence worldwide with over 300,000 hospitalizations occurring yearly in the United States alone. As its course and outcomes vary widely, a critical knowledge gap in the field has been a lack of accurate prognostic tools to forecast AP patients' outcomes. Despite several published studies in the last three decades, the predictive performance of published prognostic models has been found to be suboptimal. Recently, non-regression machine learning models (ML) have garnered intense interest in medicine for their potential for better predictive performance. Each year, an increasing number of AP models are being published. However, their methodologic quality relating to transparent reporting and risk of bias in study design has never been systematically appraised. Therefore, through collaboration between a group of clinicians and data scientists with appropriate content expertise, we will perform a systematic review of papers published between January 2021 and December 2023 containing artificial intelligence prognostic models in AP. To systematically assess these studies, the authors will leverage the CHARMS checklist, PROBAST tool for risk of bias assessment, and the most current version of the TRIPOD-AI. (Research Registry ( http://www.reviewregistry1727 .).

4.
Pancreas ; 53(5): e416-e423, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38530954

RESUMEN

OBJECTIVES: Chronic pancreatitis (CP) is an inflammatory disease affecting the absorption of fat-soluble nutrients. Signaling in pancreatic cells that lead to inflammation may be influenced by fatty acids (FAs) through diet and de novo lipogenesis. Here, we investigated the relationship between plasma FA composition in CP with heterogeneity of etiology and complications of CP. MATERIALS AND METHODS: Blood and clinical parameters were collected from subjects with CP (n = 47) and controls (n = 22). Plasma was analyzed for FA composition using gas chromatography and compared between controls and CP and within CP. RESULTS: Palmitic acid increased, and linoleic acid decreased in CP compared with controls. Correlations between age or body mass index and FAs are altered in CP compared with controls. Diabetes, pancreatic calcifications, and substance usage, but not exocrine pancreatic dysfunction, were associated with differences in oleic acid and linoleic acid relative abundance in CP. De novo lipogenesis index was increased in the plasma of subjects with CP compared with controls and in calcific CP compared with noncalcific CP. CONCLUSIONS: Fatty acids that are markers of de novo lipogenesis and linoleic acid are dysregulated in CP depending on the etiology or complication. These results enhance our understanding of CP and highlight potential pathways targeting FAs for treating CP.


Asunto(s)
Ácidos Grasos , Ácido Linoleico , Pancreatitis Crónica , Humanos , Proyectos Piloto , Pancreatitis Crónica/sangre , Pancreatitis Crónica/metabolismo , Masculino , Femenino , Persona de Mediana Edad , Adulto , Ácidos Grasos/sangre , Ácido Linoleico/sangre , Estudios de Casos y Controles , Lipogénesis , Anciano , Ácido Palmítico/sangre , Ácido Oléico/sangre , Biomarcadores/sangre
5.
Pancreatology ; 24(2): 289-297, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38238194

RESUMEN

AIMS: A novel large surface area microparticle paclitaxel (LSAM-PTX) has unique properties of long retention in cystic spaces while maintaining high drug concentration. We prospectively evaluated the safety and response of EUS-guided fine needle injection (EUS-FNI) of LSAM-PTX to chemoablate branch duct (BD)-IPMNs. METHODS: Subjects diagnosed with BD-IPMNs exhibiting at least one worrisome criteria and considered non-surgical were enrolled in a multicenter clinical trial (NCT03188991) and subsequently included in an Expanded Access Protocol (EAP) where they received EUS-FNI of LSAM-PTX (15 mg/mL). RESULTS: Six BD-IPMNs measuring (mean ± SD) 3.18 ± 0.76 cm in diameter among 5 subjects (mean age: 66 years) were treated by EUS-FNI of LSAM-PTX. A mean of 4 doses of LSAM-PTX (mean dose/cyst: 73 ± 31 mg) were administered, and subjects were followed for up to 32 months. The mean volume reduction/cyst ranged from 42 to 89% (9.58 ± 5.1 ml to 2.2 ± 1.1 ml (p = 0.016)). The mean surface area reduction ranged from 31 to 83% (21.9 ± 8.7 cm2 to 5.7 ± 2.5 cm2 (p = 0.009)). Higher dosing-frequency of EUS-FNI of LSAM-PTX significantly correlated with a reduction in cyst volume (R2 = 0.87, p = 0.03) and surface area (R2 = 0.83, p = 0.04). Comparing pre- and post-ablation samples, molecular analysis of the cyst fluid revealed a loss of IPMN-associated mutations in 5 cases (83.3%), while reemergence was observed in 1 case and persistence in 1 case. Intracystic changes (fibrosis/calcification) were observed in 83.3% (n = 5). One subject developed mild acute pancreatitis (1 of 22 EUS-FNIs of LSAM-PTX). CONCLUSION: In this EAP, EUS-FNI of LSAM-PTX into BD-IPMNs was safe and resulted in volume and surface area reduction, morphological changes, and loss of pathogenic mutations.


Asunto(s)
Carcinoma Ductal Pancreático , Quistes , Neoplasias Quísticas, Mucinosas y Serosas , Neoplasias Pancreáticas , Pancreatitis , Humanos , Anciano , Carcinoma Ductal Pancreático/patología , Enfermedad Aguda , Estudios Retrospectivos , Neoplasias Pancreáticas/patología , Estudios Multicéntricos como Asunto
6.
Clin Transl Gastroenterol ; 15(4): e00686, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38284831

RESUMEN

INTRODUCTION: Chronic pancreatitis (CP) is a progressive fibroinflammatory disorder lacking therapies and biomarkers. Neutrophil gelatinase-associated lipocalin (NGAL) is a proinflammatory cytokine elevated during inflammation that binds fatty acids (FAs) such as linoleic acid. We hypothesized that systemic NGAL could serve as a biomarker for CP and, with FAs, provide insights into inflammatory and metabolic alterations. METHODS: NGAL was measured by immunoassay, and FA composition was measured by gas chromatography in plasma (n = 171) from a multicenter study, including controls (n = 50), acute and recurrent acute pancreatitis (AP/RAP) (n = 71), and CP (n = 50). Peripheral blood mononuclear cells (PBMCs) from controls (n = 16), AP/RAP (n = 17), and CP (n = 15) were measured by cytometry by time-of-flight. RESULTS: Plasma NGAL was elevated in subjects with CP compared with controls (area under the curve [AUC] = 0.777) or AP/RAP (AUC = 0.754) in univariate and multivariate analyses with sex, age, body mass index, and smoking (control AUC = 0.874; AP/RAP AUC = 0.819). NGAL was elevated in CP and diabetes compared with CP without diabetes ( P < 0.001). NGAL + PBMC populations distinguished CP from controls (AUC = 0.950) or AP/RAP (AUC = 0.941). Linoleic acid was lower, whereas dihomo-γ-linolenic and adrenic acids were elevated in CP ( P < 0.05). Linoleic acid was elevated in CP with diabetes compared with CP subjects without diabetes ( P = 0.0471). DISCUSSION: Elevated plasma NGAL and differences in NGAL + PBMCs indicate an immune response shift that may serve as biomarkers of CP. The potential interaction of FAs and NGAL levels provide insights into the metabolic pathophysiology and improve diagnostic classification of CP.


Asunto(s)
Biomarcadores , Lipocalina 2 , Pancreatitis Crónica , Humanos , Masculino , Femenino , Lipocalina 2/sangre , Pancreatitis Crónica/sangre , Pancreatitis Crónica/diagnóstico , Persona de Mediana Edad , Biomarcadores/sangre , Adulto , Estudios Transversales , Leucocitos Mononucleares/metabolismo , Anciano , Ácidos Grasos/sangre , Ácidos Grasos/metabolismo , Ácido Linoleico/sangre , Estudios de Casos y Controles
7.
Pancreatology ; 23(8): 900-903, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37839923

RESUMEN

Diabetes mellitus following an episode of acute pancreatitis (AP) is an increasingly discussed complication, but there are sparse prospective data on the incidence and risk factors. We evaluated data from a prospective, multicenter observational cohort study that enrolled adults hospitalized with AP between 2017 and 2021 and followed them for one year. Ninety-eight participants who completed 12-month follow-up were included in this analysis. Diabetes status was assessed using a combination of measured glycated hemoglobin (HbA1c) at predetermined time intervals or physician diagnosis. In 68 participants without diabetes at enrollment, the cumulative incidence of new-onset diabetes was 4.4 % (n = 3) at 3 months and 10.3 % (n = 7) at 12 months. No differences were observed in demographic or pancreatitis-related characteristics between those who did versus did not develop diabetes, in part due to small sample size. In summary, new-onset diabetes was identified in approximately 10 % within one year after an episode of AP. Larger prospective studies are needed to further define the incidence, risk factors, and mechanisms of diabetes and pre-diabetes following AP. NCT03063398.


Asunto(s)
Diabetes Mellitus , Pancreatitis , Adulto , Humanos , Pancreatitis/etiología , Pancreatitis/complicaciones , Enfermedad Aguda , Estudios Prospectivos , Diabetes Mellitus/epidemiología , Factores de Riesgo
8.
Biomimetics (Basel) ; 8(6)2023 Oct 19.
Artículo en Inglés | MEDLINE | ID: mdl-37887627

RESUMEN

Despite the increasing rate of detection of incidental pancreatic cystic lesions (PCLs), current standard-of-care methods for their diagnosis and risk stratification remain inadequate. Intraductal papillary mucinous neoplasms (IPMNs) are the most prevalent PCLs. The existing modalities, including endoscopic ultrasound and cyst fluid analysis, only achieve accuracy rates of 65-75% in identifying carcinoma or high-grade dysplasia in IPMNs. Furthermore, surgical resection of PCLs reveals that up to half exhibit only low-grade dysplastic changes or benign neoplasms. To reduce unnecessary and high-risk pancreatic surgeries, more precise diagnostic techniques are necessary. A promising approach involves integrating existing data, such as clinical features, cyst morphology, and data from cyst fluid analysis, with confocal endomicroscopy and radiomics to enhance the prediction of advanced neoplasms in PCLs. Artificial intelligence and machine learning modalities can play a crucial role in achieving this goal. In this review, we explore current and future techniques to leverage these advanced technologies to improve diagnostic accuracy in the context of PCLs.

9.
iScience ; 26(8): 107408, 2023 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-37554459

RESUMEN

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with high metastasis and therapeutic resistance. Activating transcription factor 4 (ATF4), a master regulator of cellular stress, is exploited by cancer cells to survive. Prior research and data reported provide evidence that high ATF4 expression correlates with worse overall survival in PDAC. Tomatidine, a natural steroidal alkaloid, is associated with inhibition of ATF4 signaling in multiple diseases. Here, we discovered that in vitro and in vivo tomatidine treatment of PDAC cells inhibits tumor growth. Tomatidine inhibited nuclear translocation of ATF4 and reduced the transcriptional binding of ATF4 with downstream promoters. Tomatidine enhanced gemcitabine chemosensitivity in 3D ECM-hydrogels and in vivo. Tomatidine treatment was associated with induction of ferroptosis signaling validated by increased lipid peroxidation, mitochondrial biogenesis, and decreased GPX4 expression in PDAC cells. This study highlights a possible therapeutic approach utilizing a plant-derived metabolite, tomatidine, to target ATF4 activity in PDAC.

10.
Gastrointest Endosc ; 98(6): 953-964, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37473969

RESUMEN

BACKGROUND AND AIMS: Data on how to teach endosonographers needle-based confocal laser endomicroscopy (nCLE)-guided histologic diagnosis of pancreatic cystic lesions (PCLs) are limited. Hence, we developed and tested a structured educational program to train early-career endosonographers in nCLE-guided diagnosis of PCLs. METHODS: Twenty-one early-career nCLE-naïve endosonographers watched a teaching module outlining nCLE criteria for diagnosing PCLs. Participants then reviewed 80 high-yield nCLE videos, recorded diagnoses, and received expert feedback (phase 1). Observers were then randomized to a refresher feedback session or self-learning at 4 weeks. Eight weeks after training, participants independently assessed the same 80 nCLE videos without feedback and provided histologic predictions (phase 2). Diagnostic performance of nCLE to differentiate mucinous versus nonmucinous PCLs and to diagnose specific subtypes were analyzed using histopathology as the criterion standard. Learning curves were determined using cumulative sum analysis. RESULTS: Accuracy and diagnostic confidence for differentiating mucinous versus nonmucinous PCLs improved as endosonographers progressed through nCLE videos in phase 1 (P < .001). Similar trends were observed with the diagnosis of PCL subtypes. Most participants achieved competency interpreting nCLE, requiring a median of 38 assessments (range, 9-67). During phase 2, participants independently differentiated PCLs with high accuracy (89%), high confidence (83%), and substantial interobserver agreement (κ = .63). Accuracy for nCLE-guided PCL subtype diagnoses ranged from 82% to 96%. The learned nCLE skills did not deteriorate at 8 weeks and were not impacted by a refresher session. CONCLUSIONS: We developed a practical, effective, and durable educational intervention to train early-career endosonographers in nCLE-guided diagnosis of PCLs.


Asunto(s)
Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Quiste Pancreático , Humanos , Estudios Prospectivos , Microscopía Confocal , Quiste Pancreático/diagnóstico por imagen , Quiste Pancreático/patología , Rayos Láser
11.
Am J Gastroenterol ; 118(12): 2258-2266, 2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-37428139

RESUMEN

INTRODUCTION: Recent pilot trials in acute pancreatitis (AP) found that lactated ringers (LR) usage may result in decreased risk of moderately severe/severe AP compared with normal saline, but their small sample sizes limit statistical power. We investigated whether LR usage is associated with improved outcomes in AP in an international multicenter prospective study. METHODS: Patients directly admitted with the diagnosis of AP were prospectively enrolled at 22 international sites between 2015 and 2018. Demographics, fluid administration, and AP severity data were collected in a standardized prospective manner to examine the association between LR and AP severity outcomes. Mixed-effects logistic regression analysis was performed to determine the direction and magnitude of the relationship between the type of fluid administered during the first 24 hours and the development of moderately severe/severe AP. RESULTS: Data from 999 patients were analyzed (mean age 51 years, female 52%, moderately severe/severe AP 24%). Usage of LR during the first 24 hours was associated with reduced odds of moderately severe/severe AP (adjusted odds ratio 0.52; P = 0.014) compared with normal saline after adjusting for region of enrollment, etiology, body mass index, and fluid volume and accounting for the variation across centers. Similar results were observed in sensitivity analyses eliminating the effects of admission organ failure, etiology, and excessive total fluid volume. DISCUSSION: LR administration in the first 24 hours of hospitalization was associated with improved AP severity. A large-scale randomized clinical trial is needed to confirm these findings.


Asunto(s)
Pancreatitis , Desequilibrio Hidroelectrolítico , Humanos , Femenino , Persona de Mediana Edad , Pancreatitis/complicaciones , Estudios Prospectivos , Solución Salina , Enfermedad Aguda , Índice de Severidad de la Enfermedad , Hospitalización
12.
Am J Physiol Gastrointest Liver Physiol ; 325(3): G279-G285, 2023 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-37461868

RESUMEN

During acute pancreatitis (AP), free fatty acids (FFAs) are liberated from circulating triglycerides (TG) and injured adipocytes by pancreatic lipase. Circulating FFAs have been suspected as a source of systemic lipotoxicity in AP. However, assessment of FFAs is difficult and time-consuming, and little is known about relative levels of FFAs between patients with different severities of AP and controls. This study's aims were to assess early circulating levels of FFAs, (both saturated and unsaturated) in patients with AP vs. controls, and associations between FFA levels and AP severity. Serum samples from patients with AP were collected at enrollment (day 1 of hospital stay); serum samples were also collected from controls. FFAs including palmitic, palmitoleic, stearic, oleic, and linoleic acid were extracted and quantitated using gas chromatography separation. Severity of AP was determined by Revised Atlanta Classification. Differences in FFA levels and percentages of total FFAs were assessed between patients with AP and controls and patients with AP of different severity grades. A total of 93 patients with AP (48 female, 52%) and 29 controls (20 female, 69%) were enrolled. Of the patients with AP, 74 had mild/moderate and 19 had severe AP. Serum levels of all FFAs except stearic acid were significantly higher in patients with AP compared with controls. A strong and independent association between elevated palmitoleic acid levels and severe AP was found. Serum unsaturated FFA levels, specifically palmitoleic acid, appear to correlate with severe AP. These findings have potential clinical implications for targeted AP therapies.NEW & NOTEWORTHY Drivers of the inflammatory response in acute pancreatitis remain incompletely understood. Unsaturated fatty acids, specifically palmitoleic, appear to have an association with more severe acute pancreatitis. This finding presents a new clinical understanding of fatty acid toxicity and highlights a potential future target for treatment in severe acute pancreatitis.


Asunto(s)
Ácidos Grasos no Esterificados , Insuficiencia Multiorgánica , Pancreatitis , Humanos , Enfermedad Aguda , Ácidos Grasos no Esterificados/sangre , Ácidos Grasos Insaturados/sangre , Insuficiencia Multiorgánica/etiología , Insuficiencia Multiorgánica/metabolismo , Estudios de Casos y Controles
13.
Neuropsychopharmacology ; 48(8): 1194-1200, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37147429

RESUMEN

Prior studies show that individuals with alcohol use disorder exhibit exaggerated behavioral and brain reactivity to uncertain threats (U-threat). It is posited this brain-based factor emerges early in life and contributes to the onset and escalation of alcohol problems. However, no study to date has tested this theory using a longitudinal within-subjects design. Ninety-five young adults, ages 17-19, with minimal alcohol exposure and established risk factors for alcohol use disorder participated in this multi-session study with a 1-year tracking period. Startle eyeblink potentiation and brain activation were collected at separate baseline sessions during the well-validated No-Predictable-Unpredictable (NPU) threat-of-shock task designed to probe reactivity to U-threat and predictable threat (P-threat). Participants self-reported their drinking behavior over the past 90 days at baseline and one-year later. We fit a series of multilevel hurdle models to model the binary outcome of whether binge drinking occurred and the continuous outcome of number of binge drinking episodes. Zero-inflated binary submodels revealed that greater baseline startle reactivity, bilateral anterior insula (AIC) reactivity, and dorsal anterior cingulate cortex (dACC) reactivity to U-threat were associated with increased probability of binge drinking. There were no other associations between reactivity to U- and P-threat and probability of binge drinking and number of binging episodes. These results demonstrate that exaggerated reactivity to U-threat is a brain-based individual difference factor that connotes risk for problem drinking. These findings also add to a growing literature implicating AIC and dACC dysfunction in the pathophysiology of alcohol use disorder.


Asunto(s)
Alcoholismo , Consumo Excesivo de Bebidas Alcohólicas , Adulto Joven , Humanos , Adolescente , Encéfalo/diagnóstico por imagen , Incertidumbre , Consumo de Bebidas Alcohólicas
14.
Cancers (Basel) ; 15(9)2023 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-37173876

RESUMEN

Pancreatic cancer is projected to become the second leading cause of cancer-related mortality in the United States by 2030. This is in part due to the paucity of reliable screening and diagnostic options for early detection. Amongst known pre-malignant pancreatic lesions, pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasms (IPMNs) are the most prevalent. The current standard of care for the diagnosis and classification of pancreatic cystic lesions (PCLs) involves cross-sectional imaging studies and endoscopic ultrasound (EUS) and, when indicated, EUS-guided fine needle aspiration and cyst fluid analysis. However, this is suboptimal for the identification and risk stratification of PCLs, with accuracy of only 65-75% for detecting mucinous PCLs. Artificial intelligence (AI) is a promising tool that has been applied to improve accuracy in screening for solid tumors, including breast, lung, cervical, and colon cancer. More recently, it has shown promise in diagnosing pancreatic cancer by identifying high-risk populations, risk-stratifying premalignant lesions, and predicting the progression of IPMNs to adenocarcinoma. This review summarizes the available literature on artificial intelligence in the screening and prognostication of precancerous lesions in the pancreas, and streamlining the diagnosis of pancreatic cancer.

15.
United European Gastroenterol J ; 11(4): 383-391, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37096304

RESUMEN

BACKGROUND: Multisystem organ failure (MSOF) is the most important determinant of mortality in acute pancreatitis (AP). Obesity and alcoholic etiology have been examined as potential risk factors for MSOF, but prior studies have not adequately elucidated their independent effects on the risk of MSOF. OBJECTIVE: We aimed to determine the adjusted effects of body mass index (BMI) and alcoholic etiology on the risk of MSOF in subjects with AP. METHODS: A prospective observational study of 22 centers from 10 countries was conducted. Patients admitted to an APPRENTICE consortium center with AP between August 2015 and January 2018 were enrolled. Multivariable logistic regression was used to estimate the adjusted effects of BMI, etiology, and other relevant covariates on the risk of MSOF. Models were stratified by sex. RESULTS: Among 1544 AP subjects, there was a sex-dependent association between BMI and the risk of MSOF. Increasing BMI was associated with increased odds of MSOF in males (OR 1.10, 95% confidence interval [CI] 1.04-1.15) but not in females (OR 0.98, 95% CI 0.90-1.1). Male subjects with AP, whose BMIs were 30-34 and >35 kg/m2 , had odds ratios of 3.78 (95% CI 1.62-8.83) and 3.44 (95% CI 1.08-9.99), respectively. In females, neither higher grades of obesity nor increasing age increased the risk of MSOF. Alcoholic etiology was independently associated with increased odds of MSOF compared with non-alcohol etiologies (OR 4.17, 95% CI 2.16-8.05). CONCLUSION: Patients with alcoholic etiology and obese men (but not women) are at substantially increased risk of MSOF in AP.


Asunto(s)
Pancreatitis , Femenino , Humanos , Masculino , Pancreatitis/diagnóstico , Pancreatitis/epidemiología , Pancreatitis/etiología , Enfermedad Aguda , Factores de Riesgo , Obesidad/complicaciones , Obesidad/epidemiología , Insuficiencia Multiorgánica/diagnóstico , Insuficiencia Multiorgánica/epidemiología , Insuficiencia Multiorgánica/etiología
16.
Pediatr Cardiol ; 44(5): 1118-1124, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37099209

RESUMEN

We sought to examine current practices and changes in practice regarding initial counseling for families of patients with hypoplastic left heart syndrome (HLHS) given the evolution of options and outcomes over time. Counseling (Norwood with Blalock-Taussig-Thomas shunt (NW-BTT), NW with right ventricle to pulmonary artery conduit (NW-RVPA), hybrid palliation, heart transplantation, or non-intervention/hospice (NI)) for patients with HLHS were queried via questionnaire of pediatric care professionals in 2021 and compared to identical questionnaire from 2011. Of 322 respondents in 2021 (39% female), 299 respondents were cardiologists (92.9%), 17cardiothoracic surgeons (5.3%), and 6 were nurse practitioners (1.9%). Respondents were largely from North America (96.9%). In 2021, NW-RVPA procedure was the preferred palliation for standard risk HLHS patient (61%) and was preferred across all US regions (p < 0.001). NI was offered as an option by 71.4% of respondents for standard risk patients and was the predominant strategy for patients with end-organ dysfunction, chromosomal abnormality, and prematurity (52%, 44%, and 45%, respectively). The hybrid procedure was preferred for low birth-weight infants (51%). In comparison to the identical 2011 questionnaire (n = 200), the NW-RVPA was endorsed more in 2021 (61% vs 52%, p = 0.04). For low birth-weight infants, hybrid procedure was more recommended than in 2011 (51% vs 21%, p < 0.001). The NW-RVPA operation is the most recommended strategy throughout the US for infants with HLHS. The hybrid procedure for low birth-weight infants is increasingly recommended. NI continues to be offered even in standard risk patients with HLHS.


Asunto(s)
Procedimiento de Blalock-Taussing , Trasplante de Corazón , Síndrome del Corazón Izquierdo Hipoplásico , Procedimientos de Norwood , Lactante , Niño , Humanos , Femenino , Masculino , Síndrome del Corazón Izquierdo Hipoplásico/cirugía , Procedimiento de Blalock-Taussing/métodos , Arteria Pulmonar/cirugía , Ventrículos Cardíacos , Consejo , Resultado del Tratamiento , Procedimientos de Norwood/métodos , Estudios Retrospectivos
17.
J Heart Lung Transplant ; 42(9): 1233-1241, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37088341

RESUMEN

BACKGROUND: The 2016 revision of the US Pediatric Heart Allocation Policy developed stringent rules for priority status creating impetus for clinicians to seek status exceptions. We hypothesized there may be differential status exceptions based on race and socioeconomic status (SES) contributing to disparities in waitlist outcomes. METHODS: The Scientific Registry for Transplant Recipients was queried for children listed for heart transplant from 2012 to 2020. Waitlist status & mortality with regards to race and neighborhood SES were stratified by listing before (Era 1) or after (Era 2) the policy change. RESULTS: The use of both 1A and 1B exceptions (E) increased in Era 2. In Era 1, there was no association between patient race or neighborhood SES on use of 1A(E) or 1B(E) when controlling for age and diagnosis. In Era 2, neither race nor neighborhood SES were associated with 1A(E), but both were associated with 1B(E): non-Hispanic (NH) Black children and those from low- and middle-SES neighborhoods were significantly less likely to be listed 1B(E). In Era 1, there were no significant differences in waitlist mortality based on race at any waitlist status; in Era 2, NH Black children had higher waitlist mortality when initially listed 1B or 2. CONCLUSIONS: Since the 2016 policy change, racial disparities in waitlist mortality have worsened among children initially listed with lower priority status. Unequal use of 1B exceptions, which lower waitlist mortality, may explain some of these disparities. Recently implemented standardized pediatric exception guidance has the potential to improve equity.


Asunto(s)
Trasplante de Corazón , Obtención de Tejidos y Órganos , Humanos , Niño , Disparidades Socioeconómicas en Salud , Etnicidad , Políticas , Listas de Espera , Estudios Retrospectivos
18.
Soc Work Health Care ; 62(2-4): 107-120, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36946209

RESUMEN

There are currently no national data regarding U.S. Primary Care Physicians' (PCPs') suicide screening practices. This study surveyed 302 U.S. PCPs about their current suicide screening practices to identify service gaps and intervention points for social workers. Although one-third of PCPs reported providing screening and safety planning, few were using evidence-based tools. Factors that increased the likelihood of routine screening were belief in the importance of screening (p < .01), time (p < .01), and access to co-located behavioral health (p < .01). Findings support the role of social workers in primary care and suggest areas for training and collaboration.


Asunto(s)
Médicos de Atención Primaria , Trabajadores Sociales , Humanos , Prevención del Suicidio , Pautas de la Práctica en Medicina , Atención Primaria de Salud
19.
bioRxiv ; 2023 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-36711757

RESUMEN

Objectives: Chronic pancreatitis (CP) is an inflammatory disease that affects the absorption of nutrients like fats. Molecular signaling in pancreatic cells can be influenced by fatty acids (FAs) and changes in FA abundance could impact CP-associated complications. Here, we investigated FA abundance in CP compared to controls and explored how CP-associated complications and risk factors affect FA abundance. Methods: Blood and clinical parameters were collected from subjects with (n=47) and without CP (n=22). Plasma was analyzed for relative FA abundance using gas chromatography and compared between controls and CP. Changes in FA abundance due to clinical parameters were also assessed in both groups. Results: Decreased relative abundance of polyunsaturated fatty acids (PUFAs) and increased monounsaturated fatty acids (MUFAs) were observed in subjects with CP in a sex-dependent manner. The relative abundance of linoleic acid increased, and oleic acid decreased in CP subjects with exocrine pancreatic dysfunction and a history of substance abuse. Conclusions: Plasma FAs like linoleic acid are dysregulated in CP in a sex-dependent manner. Additionally, risk factors and metabolic dysfunction further dysregulate FA abundance in CP. These results enhance our understanding of CP and highlight potential novel targets and metabolism-related pathways for treating CP.

20.
Biomimetics (Basel) ; 7(2)2022 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-35735595

RESUMEN

The rate of incidentally detected pancreatic cystic lesions (PCLs) has increased over the past decade and was recently reported at 8%. These lesions pose a unique challenge, as each subtype of PCL carries a different risk of malignant transformation, ranging from 0% (pancreatic pseudocyst) to 34-68% (main duct intraductal papillary mucinous neoplasm). It is imperative to correctly risk-stratify the malignant potential of these lesions in order to provide the correct care course for the patient, ranging from monitoring to surgical intervention. Even with the multiplicity of guidelines (i.e., the American Gastroenterology Association guidelines and Fukuoka/International Consensus guidelines) and multitude of diagnostic information, risk stratification of PCLs falls short. Studies have reported that 25-64% of patients undergoing PCL resection have pancreatic cysts with no malignant potential, and up to 78% of mucin-producing cysts resected harbor no malignant potential on pathological evaluation. Clinicians are now incorporating artificial intelligence technology to aid in the management of these difficult lesions. This review article focuses on advancements in artificial intelligence within digital pathomics, radiomics, and genomics as they apply to the diagnosis and risk stratification of PCLs.

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