1.Global epidemiology of alcohol-related liver disease, liver cancer, and alcohol use disorder, 2000–2021
Pojsakorn DANPANICHKUL ; Luis Antonio DÍAZ ; Kanokphong SUPARAN ; Primrose TOTHANARUNGROJ ; Supapitch SIRIMANGKLANURAK ; Thanida AUTTAPRACHA ; Hanna L. BLANEY ; Banthoon SUKPHUTANAN ; Yanfang PANG ; Siwanart KONGARIN ; Francisco IDALSOAGA ; Eduardo FUENTES-LÓPEZ ; Lorenzo LEGGIO ; Mazen NOUREDDIN ; Trenton M. WHITE ; Alexandre LOUVET ; Philippe MATHURIN ; Rohit LOOMBA ; Patrick S. KAMATH ; Jürgen REHM ; Jeffrey V. LAZARUS ; Karn WIJARNPREECHA ; Juan Pablo ARAB
Clinical and Molecular Hepatology 2025;31(2):525-547
Background/Aims:
Alcohol represents a leading burden of disease worldwide, including alcohol use disorder (AUD) and alcohol-related liver disease (ALD). We aim to assess the global burden of AUD, ALD, and alcohol-attributable primary liver cancer between 2000–2021.
Methods:
We registered the global and regional trends of AUD, ALD, and alcohol-related liver cancer using data from the Global Burden of Disease 2021 Study, the largest and most up-to-date global epidemiology database. We estimated the annual percent change (APC) and its 95% confidence interval (CI) to assess changes in age-standardized rates over time.
Results:
In 2021, there were 111.12 million cases of AUD, 3.02 million cases of ALD, and 132,030 cases of alcohol-attributable primary liver cancer. Between 2000 and 2021, there was a 14.66% increase in AUD, a 38.68% increase in ALD, and a 94.12% increase in alcohol-attributable primary liver cancer prevalence. While the age-standardized prevalence rate for liver cancer from alcohol increased (APC 0.59%; 95% confidence interval [CI] 0.52 to 0.67%) over these years, it decreased for ALD (APC –0.71%; 95% CI –0.75 to –0.67%) and AUD (APC –0.90%; 95% CI –0.94 to –0.86%). There was significant variation by region, socioeconomic development level, and sex. During the last years (2019–2021), the prevalence, incidence, and death of ALD increased to a greater extent in females.
Conclusions
Given the high burden of AUD, ALD, and alcohol-attributable primary liver cancer, urgent measures are needed to prevent them at both global and national levels.
2.Global epidemiology of alcohol-related liver disease, liver cancer, and alcohol use disorder, 2000–2021
Pojsakorn DANPANICHKUL ; Luis Antonio DÍAZ ; Kanokphong SUPARAN ; Primrose TOTHANARUNGROJ ; Supapitch SIRIMANGKLANURAK ; Thanida AUTTAPRACHA ; Hanna L. BLANEY ; Banthoon SUKPHUTANAN ; Yanfang PANG ; Siwanart KONGARIN ; Francisco IDALSOAGA ; Eduardo FUENTES-LÓPEZ ; Lorenzo LEGGIO ; Mazen NOUREDDIN ; Trenton M. WHITE ; Alexandre LOUVET ; Philippe MATHURIN ; Rohit LOOMBA ; Patrick S. KAMATH ; Jürgen REHM ; Jeffrey V. LAZARUS ; Karn WIJARNPREECHA ; Juan Pablo ARAB
Clinical and Molecular Hepatology 2025;31(2):525-547
Background/Aims:
Alcohol represents a leading burden of disease worldwide, including alcohol use disorder (AUD) and alcohol-related liver disease (ALD). We aim to assess the global burden of AUD, ALD, and alcohol-attributable primary liver cancer between 2000–2021.
Methods:
We registered the global and regional trends of AUD, ALD, and alcohol-related liver cancer using data from the Global Burden of Disease 2021 Study, the largest and most up-to-date global epidemiology database. We estimated the annual percent change (APC) and its 95% confidence interval (CI) to assess changes in age-standardized rates over time.
Results:
In 2021, there were 111.12 million cases of AUD, 3.02 million cases of ALD, and 132,030 cases of alcohol-attributable primary liver cancer. Between 2000 and 2021, there was a 14.66% increase in AUD, a 38.68% increase in ALD, and a 94.12% increase in alcohol-attributable primary liver cancer prevalence. While the age-standardized prevalence rate for liver cancer from alcohol increased (APC 0.59%; 95% confidence interval [CI] 0.52 to 0.67%) over these years, it decreased for ALD (APC –0.71%; 95% CI –0.75 to –0.67%) and AUD (APC –0.90%; 95% CI –0.94 to –0.86%). There was significant variation by region, socioeconomic development level, and sex. During the last years (2019–2021), the prevalence, incidence, and death of ALD increased to a greater extent in females.
Conclusions
Given the high burden of AUD, ALD, and alcohol-attributable primary liver cancer, urgent measures are needed to prevent them at both global and national levels.
3.Global epidemiology of alcohol-related liver disease, liver cancer, and alcohol use disorder, 2000–2021
Pojsakorn DANPANICHKUL ; Luis Antonio DÍAZ ; Kanokphong SUPARAN ; Primrose TOTHANARUNGROJ ; Supapitch SIRIMANGKLANURAK ; Thanida AUTTAPRACHA ; Hanna L. BLANEY ; Banthoon SUKPHUTANAN ; Yanfang PANG ; Siwanart KONGARIN ; Francisco IDALSOAGA ; Eduardo FUENTES-LÓPEZ ; Lorenzo LEGGIO ; Mazen NOUREDDIN ; Trenton M. WHITE ; Alexandre LOUVET ; Philippe MATHURIN ; Rohit LOOMBA ; Patrick S. KAMATH ; Jürgen REHM ; Jeffrey V. LAZARUS ; Karn WIJARNPREECHA ; Juan Pablo ARAB
Clinical and Molecular Hepatology 2025;31(2):525-547
Background/Aims:
Alcohol represents a leading burden of disease worldwide, including alcohol use disorder (AUD) and alcohol-related liver disease (ALD). We aim to assess the global burden of AUD, ALD, and alcohol-attributable primary liver cancer between 2000–2021.
Methods:
We registered the global and regional trends of AUD, ALD, and alcohol-related liver cancer using data from the Global Burden of Disease 2021 Study, the largest and most up-to-date global epidemiology database. We estimated the annual percent change (APC) and its 95% confidence interval (CI) to assess changes in age-standardized rates over time.
Results:
In 2021, there were 111.12 million cases of AUD, 3.02 million cases of ALD, and 132,030 cases of alcohol-attributable primary liver cancer. Between 2000 and 2021, there was a 14.66% increase in AUD, a 38.68% increase in ALD, and a 94.12% increase in alcohol-attributable primary liver cancer prevalence. While the age-standardized prevalence rate for liver cancer from alcohol increased (APC 0.59%; 95% confidence interval [CI] 0.52 to 0.67%) over these years, it decreased for ALD (APC –0.71%; 95% CI –0.75 to –0.67%) and AUD (APC –0.90%; 95% CI –0.94 to –0.86%). There was significant variation by region, socioeconomic development level, and sex. During the last years (2019–2021), the prevalence, incidence, and death of ALD increased to a greater extent in females.
Conclusions
Given the high burden of AUD, ALD, and alcohol-attributable primary liver cancer, urgent measures are needed to prevent them at both global and national levels.
4.Implementation of Society for Cardiovascular Angiography and Interventions classification in patients with cardiogenic shock secondary to acute myocardial infarction in a spanish university hospital
Javier Pérez CERVERA ; Carlos Antonio Aranda LÓPEZ ; Rosa Navarro ROMERO ; Javier Corral MACÍAS ; Juan Manuel Nogales ASENSIO ; José Ramón López MÍNGUEZ
Acute and Critical Care 2024;39(2):257-265
Killip-Kimball classification has been used for estimating death risk in patients suffering acute myocardial infarction (AMI). Killip-Kimball stage IV corresponds to cardiogenic shock. However, the Society for Cardiovascular Angiography and Interventions (SCAI) classification provides a more precise tool to classify patients according to shock severity. The aim of this study was to apply this classification to a cohort of Killip IV patients and to analyze the differences in death risk estimation between the two classifications. Methods: A single-center retrospective cohort study of 100 consecutive patients hospitalized for “Killip IV AMI” between 2016 and 2023 was performed to reclassify patients according to SCAI stage. Results: Distribution of patients according to SCAI stages was B=4%, C=53%, D=27%, E=16%. Thirty-day mortality increased progressively according to these stages (B=0%, C=11.88%, D=55.56%, E=87.50%; P<0.001). The exclusive use of Killip IV stage overestimated death risk compared to SCAI C (35% vs. 11.88%, P=0.002) and underestimated it compared to SCAI D and E stages (35% vs. 55.56% and 87.50%, P=0.03 and P<0.001, respectively). Age >69 years, creatinine >1.15 mg/dl and advanced SCAI stages (SCAI D and E) were independent predictors of 30-day mortality. Mechanical circulatory support use showed an almost significant benefit in advanced SCAI stages (D and E hazard ratio, 0.45; 95% confidence interval, 0.19–1.06; P=0.058). Conclusions: SCAI classification showed superior death risk estimation compared to Killip IV. Age, creatinine levels and advanced SCAI stages were independent predictors of 30-day mortality. Mechanical circulatory support could play a beneficial role in advanced SCAI stages.
5.Implementation of Society for Cardiovascular Angiography and Interventions classification in patients with cardiogenic shock secondary to acute myocardial infarction in a spanish university hospital
Javier Pérez CERVERA ; Carlos Antonio Aranda LÓPEZ ; Rosa Navarro ROMERO ; Javier Corral MACÍAS ; Juan Manuel Nogales ASENSIO ; José Ramón López MÍNGUEZ
Acute and Critical Care 2024;39(2):257-265
Killip-Kimball classification has been used for estimating death risk in patients suffering acute myocardial infarction (AMI). Killip-Kimball stage IV corresponds to cardiogenic shock. However, the Society for Cardiovascular Angiography and Interventions (SCAI) classification provides a more precise tool to classify patients according to shock severity. The aim of this study was to apply this classification to a cohort of Killip IV patients and to analyze the differences in death risk estimation between the two classifications. Methods: A single-center retrospective cohort study of 100 consecutive patients hospitalized for “Killip IV AMI” between 2016 and 2023 was performed to reclassify patients according to SCAI stage. Results: Distribution of patients according to SCAI stages was B=4%, C=53%, D=27%, E=16%. Thirty-day mortality increased progressively according to these stages (B=0%, C=11.88%, D=55.56%, E=87.50%; P<0.001). The exclusive use of Killip IV stage overestimated death risk compared to SCAI C (35% vs. 11.88%, P=0.002) and underestimated it compared to SCAI D and E stages (35% vs. 55.56% and 87.50%, P=0.03 and P<0.001, respectively). Age >69 years, creatinine >1.15 mg/dl and advanced SCAI stages (SCAI D and E) were independent predictors of 30-day mortality. Mechanical circulatory support use showed an almost significant benefit in advanced SCAI stages (D and E hazard ratio, 0.45; 95% confidence interval, 0.19–1.06; P=0.058). Conclusions: SCAI classification showed superior death risk estimation compared to Killip IV. Age, creatinine levels and advanced SCAI stages were independent predictors of 30-day mortality. Mechanical circulatory support could play a beneficial role in advanced SCAI stages.
6.Implementation of Society for Cardiovascular Angiography and Interventions classification in patients with cardiogenic shock secondary to acute myocardial infarction in a spanish university hospital
Javier Pérez CERVERA ; Carlos Antonio Aranda LÓPEZ ; Rosa Navarro ROMERO ; Javier Corral MACÍAS ; Juan Manuel Nogales ASENSIO ; José Ramón López MÍNGUEZ
Acute and Critical Care 2024;39(2):257-265
Killip-Kimball classification has been used for estimating death risk in patients suffering acute myocardial infarction (AMI). Killip-Kimball stage IV corresponds to cardiogenic shock. However, the Society for Cardiovascular Angiography and Interventions (SCAI) classification provides a more precise tool to classify patients according to shock severity. The aim of this study was to apply this classification to a cohort of Killip IV patients and to analyze the differences in death risk estimation between the two classifications. Methods: A single-center retrospective cohort study of 100 consecutive patients hospitalized for “Killip IV AMI” between 2016 and 2023 was performed to reclassify patients according to SCAI stage. Results: Distribution of patients according to SCAI stages was B=4%, C=53%, D=27%, E=16%. Thirty-day mortality increased progressively according to these stages (B=0%, C=11.88%, D=55.56%, E=87.50%; P<0.001). The exclusive use of Killip IV stage overestimated death risk compared to SCAI C (35% vs. 11.88%, P=0.002) and underestimated it compared to SCAI D and E stages (35% vs. 55.56% and 87.50%, P=0.03 and P<0.001, respectively). Age >69 years, creatinine >1.15 mg/dl and advanced SCAI stages (SCAI D and E) were independent predictors of 30-day mortality. Mechanical circulatory support use showed an almost significant benefit in advanced SCAI stages (D and E hazard ratio, 0.45; 95% confidence interval, 0.19–1.06; P=0.058). Conclusions: SCAI classification showed superior death risk estimation compared to Killip IV. Age, creatinine levels and advanced SCAI stages were independent predictors of 30-day mortality. Mechanical circulatory support could play a beneficial role in advanced SCAI stages.
7.Implementation of Society for Cardiovascular Angiography and Interventions classification in patients with cardiogenic shock secondary to acute myocardial infarction in a spanish university hospital
Javier Pérez CERVERA ; Carlos Antonio Aranda LÓPEZ ; Rosa Navarro ROMERO ; Javier Corral MACÍAS ; Juan Manuel Nogales ASENSIO ; José Ramón López MÍNGUEZ
Acute and Critical Care 2024;39(2):257-265
Killip-Kimball classification has been used for estimating death risk in patients suffering acute myocardial infarction (AMI). Killip-Kimball stage IV corresponds to cardiogenic shock. However, the Society for Cardiovascular Angiography and Interventions (SCAI) classification provides a more precise tool to classify patients according to shock severity. The aim of this study was to apply this classification to a cohort of Killip IV patients and to analyze the differences in death risk estimation between the two classifications. Methods: A single-center retrospective cohort study of 100 consecutive patients hospitalized for “Killip IV AMI” between 2016 and 2023 was performed to reclassify patients according to SCAI stage. Results: Distribution of patients according to SCAI stages was B=4%, C=53%, D=27%, E=16%. Thirty-day mortality increased progressively according to these stages (B=0%, C=11.88%, D=55.56%, E=87.50%; P<0.001). The exclusive use of Killip IV stage overestimated death risk compared to SCAI C (35% vs. 11.88%, P=0.002) and underestimated it compared to SCAI D and E stages (35% vs. 55.56% and 87.50%, P=0.03 and P<0.001, respectively). Age >69 years, creatinine >1.15 mg/dl and advanced SCAI stages (SCAI D and E) were independent predictors of 30-day mortality. Mechanical circulatory support use showed an almost significant benefit in advanced SCAI stages (D and E hazard ratio, 0.45; 95% confidence interval, 0.19–1.06; P=0.058). Conclusions: SCAI classification showed superior death risk estimation compared to Killip IV. Age, creatinine levels and advanced SCAI stages were independent predictors of 30-day mortality. Mechanical circulatory support could play a beneficial role in advanced SCAI stages.
8.Characterization of hypotensive and vasorelaxant effects of PHAR-DBH-Me a new cannabinoid receptor agonist
Oscar Alberto LÓPEZ-CANALES ; Natalia PAVÓN ; Laura Matilde UBALDO-REYES ; Marco Antonio JUÁREZ-OROPEZA ; Patricia Victoria TORRES-DURÁN ; Ignacio REGLA ; María Cristina PAREDES-CARBAJAL
The Korean Journal of Physiology and Pharmacology 2022;26(2):77-86
The effect of PHAR-DBH-Me, a cannabinoid receptor agonist, on different cardiovascular responses in adult male rats was analyzed. The blood pressure was measured directly and indirectly. The coronary flow was measured by Langendorff preparation, and vasomotor responses induced by PHAR-DBH-Me in aortic rings precontracted with phenylephrine (PHEN) were analyzed. The intravenous injection of the compound PHAR-DBH-Me (0.018–185 µg/kg) resulted in decreased blood pressure; maximum effect was observed at the dose of 1,850 µg/kg. A concentrationdependent increase in the coronary flow was observed in a Langendorff preparation. In the aortic rings, with and without endothelium, pre-contracted with PHEN (10–6 M), the addition of PHAR-DBH-Me to the superfusion solution (10–12 –10 –5 M), produced a vasodilator response, which depends on the concentration and presence of the endothelium. L-NAME inhibited these effects. Addition of CB 1 receptor antagonist (AM 251) did not modify the response, while CB2 receptor antagonist (AM630) decreased the potency of relaxation elicited by PHAR-DBH-Me. Indomethacin shifted the curve concentration-response to the left and produced an increase in the magnitude of the maximum endothelium dependent response to this compound. The maximum effect of PHAR-DBH-Me was observed with the concentration of 10 –5 M. These results show that PHAR-DBH-Me has a concentration-dependent and endothelium-dependent vasodilator effect through CB2 receptor. This vasodilation is probably mediated by the synthesis/release of NO. On the other hand, it is suggested that PHAR-DBH-Me also induces the release of a vasoconstrictor prostanoid.
9.Influence of Maternal Diabetes on the Risk of Neurodevelopmental Disorders in Offspring in the Prenatal and Postnatal Periods
Verónica PEREA ; Xavier URQUIZU ; Maite VALVERDE ; Marina MACIAS ; Anna CARMONA ; Esther ESTEVE ; Gemma ESCRIBANO ; Nuria PONS ; Oriol GIMÉNEZ ; Teresa GIRONÉS ; Andreu SIMÓ-SERVAT ; Andrea DOMENECH ; Núria ALONSO-CARRIL ; Carme QUIRÓS ; Antonio J. AMOR ; Eva LÓPEZ ; Maria José BARAHONA
Diabetes & Metabolism Journal 2022;46(6):912-922
Background:
This study aimed to evaluate the influence of maternal diabetes in the risk of neurodevelopmental disorders in offspring in the prenatal and postnatal periods.
Methods:
This cohort study included singleton gestational diabetes mellitus (GDM) pregnancies >22 weeks’ gestation with live newborns between 1991 and 2008. The control group was randomly selected and matched (1:2) for maternal age, weeks of gestation and birth year. Cox regression models estimated the effect of GDM on the risk of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and maternal type 2 diabetes mellitus (T2DM). Moreover, interaction between maternal T2DM and GDM-ADHD relationship was evaluated.
Results:
Children (n=3,123) were included (1,073 GDM; 2,050 control group). The median follow-up was 18.2 years (interquartile range, 14.2 to 22.3) (n=323 with ADHD, n=36 with ASD, and n=275 from women who developed T2DM). GDM exposure was associated with ADHD (hazard ratio [HR]crude, 1.67; 95% confidence interval [CI], 1.33 to 2.07) (HRadjusted, 1.64; 95% CI, 1.31 to 2.05). This association remained significant regardless of the treatment (diet or insulin) and diagnosis after 26 weeks of gestation. Children of mothers who developed T2DM presented higher rates of ADHD (14.2 vs. 10%, P=0.029). However, no interaction was found when T2DM was included in the GDM and ADHD models (P>0.05). GDM was not associated with an increased risk of ASD (HRadjusted, 1.46; 95% CI, 0.74 to 2.84).
Conclusion
Prenatal exposure to GDM increases the risk of ADHD in offspring, regardless of GDM treatment complexity. However, postnatal exposure to maternal T2DM was not related to the development of ADHD.
10.Intestinal ultrasonography and fecal calprotectin for monitoring inflammation of ileal Crohn’s disease: two complementary tests
José María PAREDES ; Tomás RIPOLLÉS ; Ángela ALGARRA ; Rafael DIAZ ; Nadia MORENO ; Patricia LATORRE ; María Jesús MARTÍNEZ ; Pilar LLOPIS ; Antonio LÓPEZ ; Eduardo MORENO-OSSET
Intestinal Research 2022;20(3):361-369
Background/Aims:
Tight control of inflammation and adjustment of treatment if activity persists is the current strategy for the management of Crohn’s disease (CD). The usefulness of fecal calprotectin (FC) in isolated involvement of the small intestine in CD is controversial. To assess the usefulness of FC to determine the inflammatory activity detected by intestinal ultrasonography (IUS) in ileal CD.
Methods:
Patients with exclusively ileal involvement CD who underwent IUS and an FC were prospectively included. Simple ultrasound index was used to determine inflammatory activity. The usual statistical tests for comparison of diagnostic techniques were used.
Results:
One hundred and five patients were included, IUS showed inflammatory activity in 59% of patients and complications in 18.1%. FC showed a significant correlation with IUS in the weak range (Spearman coefficient r=0.502; P<0.001); the area under the receiver operating characteristic curve was 0.79 (95% confidence interval, 0.70–0.88; P<0.001). The FC value that best reflected the activity in IUS was 100 μg/g with sensitivity, specificity, and positive and negative predictive values of 73.0%, 71.4%, 79.3% and 63.8%, respectively. There were no differences in FC concentration between patients with or without transmural complications. The addition of serum C-reactive protein to FC did not improve the ability to assess IUS activity.
Conclusions
FC has a significant correlation with IUS to monitor ileal CD activity. This correlation is weak and it does not allow assessing the presence of CD complications. Both tests should be used in conjunction for tight control of ileal CD. More studies on noninvasive tests in this location are needed.

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