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Alcohol-associated liver disease (ALD) rates have increased substantially in the United States (US) and elsewhere around the globe. These increases are largely the result of increases in alcohol use. While there are many levels at which alcohol use interventions can be implemented in order to reduce alcohol use and its negative health consequences, public policy initiatives have emerged as a powerful way to intervene across a population. In this narrative review, we will review major US national as well as worldwide alcohol related public health policies with a particular focus on describing how such policies have influenced rates of ALD and its complications and outcomes. We will describe global alcohol public health policy frameworks, review key alcohol policy models, describe existing notable policies and their impacts, and highlight gaps in ALD policy literature where further research and policy interventions could reduce rates mortality from ALD.
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A 59-year-old woman with polycythemia vera-related portal hypertension requiring frequent paracentesis was admitted for asymptomatic recurrent spontaneous bacterial peritonitis, which was diagnosed based on elevated polymorphonuclear (PMN) count. She had multiple similar admissions during which she was treated with antibiotics. The patient had chronic baseline leukocytosis due to polycythemia vera. Repeat paracentesis after intravenous antibiotics demonstrated persistent elevation of PMN count without clinical symptoms. A multidisciplinary team concluded that the increased PMN count was secondary to polycythemia. The patient was diagnosed with omental extramedullary hematopoiesis, a rare condition causing elevated PMN count in the absence of bacterial contamination.
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AIMS: To conduct a systematic review and meta-analysis with the aim of synthesizing existing data on the efficacy and safety of topiramate as an adjunctive treatment for reducing second-generation antipsychotic (SGA)-associated weight gain in children aged 4-18 years. METHODS: We conducted a comprehensive search of PubMed, Embase, PsychNet and Web of Science from time of their inception up to 12 February 2024, including randomized controlled trials that compared SGA treatment with and without topiramate co-administration in children. The primary outcomes were changes in body weight and body mass index (BMI). Heterogeneity was assessed using I2 statistics. RESULTS: This systematic review included five randomized trials, totalling 139 participants (43.9% female; mean [SD] age 11.9 [3.5] years). Four of these trials were included in the meta-analysis, comprising 116 subjects. We found that topiramate was significantly effective both in reducing SGA-associated weight gain, with a mean difference of -2.80 kg (95% confidence interval [CI] -5.28 to -0.31; p = 0.037, I2 = 86.7%) and a standardized mean difference (SMD) of -1.33 (95% CI -2.14 to -0.51; p = 0.014, I2 = 31.7%), and in reducing BMI change compared to placebo (SMD -1.90, 95% CI -3.09 to -0.70; p = 0.02, I2 = 0%). Sedation risk was lower with topiramate than with placebo (odds ratio 0.19, 95% CI 0.11-0.32; p < 0.01, I2 = 0%). No significant differences were found in dropouts, any other side effects, and metabolic parameters, such as triglycerides, total cholesterol, low-density lipoprotein, high-density lipoprotein, and glucose. None of the included studies reported assessments on cognitive side effects. CONCLUSION: This meta-analysis suggests that topiramate is an effective and safe option for mitigating SGA-associated weight gain in children.
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Antipsicóticos , Topiramato , Aumento de Peso , Humanos , Topiramato/uso terapêutico , Topiramato/efeitos adversos , Aumento de Peso/efeitos dos fármacos , Criança , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Adolescente , Pré-Escolar , Feminino , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Obesidade Infantil/tratamento farmacológico , Resultado do Tratamento , Índice de Massa CorporalRESUMO
BACKGROUND: Hospitalization and mortality in patients with alcohol-associated hepatitis (AH), a severe form of liver disease, continue to increase over time. Given the severity of the illness, most hospitalized patients with AH are admitted from the emergency department (ED). However, there are no data on ED utilization by patients with AH. Thus, the Nationwide Emergency Department Sample (NEDS) dataset was analyzed to determine the ED utilization for AH. METHODS: Temporal trends (2016-2019) and outcomes of ED visits for AH were determined. Primary or secondary AH diagnoses were based on coding priority. Numbers of patients evaluated in the ED, severity of disease, complications of liver disease, and discharge disposition were analyzed. Crude and adjusted rates were examined, and temporal trends evaluated using logistic regression with orthogonal polynomial contrasts for each year. RESULTS: There were 466,014,370 ED visits during 2016-2019, of which 448,984 (0.096%) were for AH, 85.0% of which required hospitalization. The rate of visits for AH (primary and secondary) between 2016 and 2019 increased from 85 to 106.8/100,000 ED visits. The rate of secondary AH increased more than the rate of primary AH (from 68.6 to 86.5 vs. from 16.4 to 20.3/100,000 ED visits). Patients aged 45-64 years had the highest rate of ED visits for AH, which decreased during the study period, while the rate of ED visits for AH increased in those aged 25-44 years (from 38.5% to 42.9%). The severity of disease (ascites, hepatic encephalopathy, and acute kidney injury) also increased over time. Medicaid and private insurance were the most common payors for patients seeking care in the ED for AH. CONCLUSIONS: Temporal trends show an overall increase in ED utilization rates for AH, more patients requiring hospitalization, and an increase in the proportion of younger patients presenting to the ED with AH.
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Liver transplant is a rare phenomenon for pyruvate kinase deficiency (PKD)-related liver disease and can be mediated by multiple mechanisms. In this report, we present a 55-year-old man with PKD who had acute-on-chronic liver failure with kidney failure and marked hyperbilirubinemia. His liver disease was from recurrent cholangitis, cholestasis from hemolysis, and iron deposition (likely from both repeated transfusions in youth and chronic hemolysis), all consequences of his PKD. He received a liver transplant and had a good outcome. Our case highlights the mechanisms of liver injury in PKD and successful transplantation for this rare complication.
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BACKGROUND AND OBJECTIVE: Alpha-1 antitrypsin deficiency (AATD) is an uncommon but underdiagnosed cause of cirrhosis and lacks medical treatment options. It is important to recognize risk factors that contribute to disease progression and liver transplantation. We aimed to assess if age, sex, or smoking status was associated with liver or lung disease progression. METHODS: Forty-three patients with ZZ-AATD cirrhosis were consecutively sampled from an Institutional Review Board-approved registry of 240 patients with AATD of any genotype seen as outpatients in the Cleveland Clinic between 1999 and 2019. To determine the association between risk factors and lung or liver disease progression, linear mixed-effects models with fixed effects for linear time, risk factor, and time-by-risk factor interaction, and the random intercepts for intra-patient correlation were used. RESULTS: Based on the mixed-effects model analysis, there was a significant association between liver disease progression and smoking history, and no association with age or sex. There was no association between lung disease progression and age, sex, or smoking history. However, smoking history was significantly associated with lower forced expiratory volume values. CONCLUSION: This study found that in a cohort of patients with PI*ZZ genotype AATD (ZZ-AATD) and cirrhosis, smoking history was associated with liver disease progression, whereas age and sex were not.
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Pneumopatias , Deficiência de alfa 1-Antitripsina , Progressão da Doença , Volume Expiratório Forçado , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , Cirrose Hepática/etiologia , alfa 1-Antitripsina/genética , Deficiência de alfa 1-Antitripsina/complicações , Deficiência de alfa 1-Antitripsina/diagnóstico , Deficiência de alfa 1-Antitripsina/epidemiologiaRESUMO
Background: The optimal cardiovascular (CV) risk stratification in liver transplant (LT) candidates remains unclear. The aim of this study was to evaluate concordance of findings between dobutamine stress echocardiography (DSE), positron emission tomography/computed tomography myocardial perfusion imaging (PET/CT MPI), and left heart catheterization in adult LT candidates. Methods: Data on 234 consecutive adult LT candidates from February 2015 to June 2018 with PET/CT MPI were reviewed. Adverse CV outcomes were adjudicated via chart review by a board-certified cardiologist. Results: Median age was 60.8, body mass index 30.2 kg/m2, and model of end-stage liver disease-sodium 14; 61% were male, and 54% had diabetes. Thirty-seven percent had nonalcoholic steatohepatitis and 29% alcohol-related liver disease. Sixty-five percent of patients had a DSE, of which 41% were nondiagnostic. No factors were independently associated with having a nondiagnostic DSE. The median global myocardial flow reserve correlated positively with hemoglobin and negatively with model of end-stage liver disease-sodium, age, ejection fraction, and body mass index. Moderate/high-risk MPIs were associated with older age and known CV disease. In patients with 2 cardiac testing modalities, findings were concordant in 87%. Eleven of 53 LT recipients experienced an adverse CV outcome, but no independent predictors were identified for this outcome. Conclusions: Results of different cardiac risk-stratification modalities were concordant across modalities the majority of the time in LT candidates, although these findings were not independently correlated with risk of post-LT CV outcomes. Given the high rates of nondiagnostic DSEs in this population, PET/CT MPI may be the preferred CV risk-stratification modality in older patients and those with known CV disease.
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Mycobacteriophage D29 infects species belonging to the genus Mycobacterium including the deadly pathogen Mycobacterium tuberculosis. D29 is a lytic phage, although, related to the lysogenic mycobacteriophage L5. This phage is unable to lysogenize in mycobacteria as it lacks the gene encoding the phage repressor. Infection by many mycobacteriophages cause various changes in the host that ultimately leads to inactivation of the latter. One of the host targets often modified in the process is RNA polymerase. During our investigations with phage D29 infected Mycobacterium smegmatis (Msm) we observed that the promoters from both phage, and to a lesser extent those of the host were found to be more active in cells that were exposed to D29, as compared to the unexposed. Further experiments indicate that the RNA polymerase purified from phage infected cells possessed higher affinity for promoters particularly those that were phage derived. Comparison of the purified RNA polymerase preparations from infected and uninfected cells showed that several ancillary transcription factors, Sigma factor F, Sigma factor H, CarD and RbpA are prominently associated with the RNA polymerase from infected cells. Based on our observations we conclude that the higher activity of RNA polymerase observed in D29 infected cells is due to its increased association with ancillary transcription factors.
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Micobacteriófagos , Mycobacterium tuberculosis , RNA Polimerases Dirigidas por DNA/genética , Lisogenia , Micobacteriófagos/genética , Mycobacterium smegmatis/genéticaRESUMO
Objective: This paper examines the incidence, clinical presentation, and pathophysiology of portal vein thrombosis (PVT) in cirrhosis. Additionally, we have reviewed the literature regarding the current status of medical and interventional radiology management of PVT and have proposed a novel algorithm for the management given different clinical scenarios. Lastly two representative cases displaying endovascular treatment options are provided. Background: Portal vein thrombus in the setting of cirrhosis is an increasingly recognized clinical issue with debate on its pathophysiology, natural course, and optimal treatment. Approximately one-third of patients are asymptomatic, and detection of the thrombus is an incidental finding on imaging performed for other reasons. In 30% to 50% of patients, PVT resolves spontaneously. However, there is increased post-transplant mortality in patients with completely occlusive PVT, therefore effective early revascularization strategies are needed for patients with complete PVT who are expected to undergo liver transplant. Additionally, no consensus has been reached regarding PVT treatment in terms of timing and type of interventions as well as type and duration of anticoagulation. Methods: Computerized literature search as well as discussion with experts in the field. Conclusions: Management of PVT is complex, as many variables affect which treatments can be used. Anticoagulation appears to be the optimal first-line treatment in patients with acute PVT but without bleeding varices or mesenteric ischemia. Minimally invasive treatments include various methods of mechanical thrombectomy, chemical thrombolysis, and transjugular intrahepatic portosystemic shunt (TIPS) placement with or without variceal embolization. Definitive recommendations are difficult due to lack of high quality data and continued research is needed to evaluate the efficacy of different anticoagulants as well as the timing and use of various minimally invasive therapies in specific circumstances.
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Rationale: The management of cystic lesions of the jaws presents a challenge to the surgeon. Marsupialisation, one of the conservative management options, has been used as a single or combined surgical treatment modality for the cystic lesions of the jaws. Patient Concerns: All patients presented with a complaint of a firm swelling of the face with one of the patients presenting with paraesthesia in the affected area. Diagnosis: Clinical and radiographic examination was carried out followed by aspiration cytology. All lesions were provisionally diagnosed with odontogenic cystic lesions. Treatment: Marsupialisation under general anaesthesia was carried out for all patients. Postoperatively, a customised obturator was fabricated. Outcomes: All the patients showed good radiological ossification postoperatively. Take-Away Lessons: The approach to larger cysts remains controversial. The long-term results following the marsupialisation of extensive cysts of this report may help surgeons to opt for a conservative approach to such lesions before aggressive options.
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MSMEG_2295 is a TetR family protein encoded by the first gene of a Mycobacterium smegmatis (Msm) operon that expresses the gene for DinB2 (MSMEG_2294), a translesion DNA repair enzyme. We have carried out investigations to understand its function by performing DNA binding studies and gene knockout experiments. We found that the protein binds to a conserved inverted repeat sequence located upstream of the dinB2 operon and several other genes. Using a knockout of MSMEG_2295, we show that MSMEG_2295 controls the expression of at least five genes, the products of which could potentially influence carbohydrate and fatty acid metabolism as well as antibiotic and oxidative stress resistance. We have demonstrated that MSMEG_2295 is a repressor by performing complementation analysis. Knocking out of MSMEG_2295 had a significant impact on pyruvate metabolism. Pyruvate dehydrogenase activity was virtually undetectable in ΔMSMEG_2295, although in the complemented strain, it was high. We also show that knocking out of MSMEG_2295 causes resistance to H2O2, reversed in the complemented strain. We have further found that the mycobacterial growth inhibitor plumbagin, a compound of plant origin, acts as an inducer of MSMEG_2295 regulated genes. We, therefore, establish that MSMEG_2295 functions by exerting its role as a repressor of multiple Msm genes and that by doing so, it plays a vital role in controlling pyruvate metabolism and response to oxidative stress.
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Proteínas de Bactérias/metabolismo , Mycobacterium smegmatis/metabolismo , Proteínas Repressoras/metabolismo , Proteínas de Bactérias/genética , DNA Bacteriano/metabolismo , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Mutação , Mycobacterium smegmatis/efeitos dos fármacos , Mycobacterium smegmatis/genética , Naftoquinonas/farmacologia , Regiões Operadoras Genéticas , Óperon/genética , Regiões Promotoras Genéticas , Ácido Pirúvico/metabolismo , Proteínas Repressoras/genética , Superóxidos/metabolismoRESUMO
AIM: This study aims to compare the level of serum beta-2 microglobulin (ß2-M) in normal healthy individuals and patient with squamous cell carcinoma (SCC). METHODOLOGY: This study has been conducted in patients attending the Department of Oral and Maxillofacial Surgery, Yenepoya Dental College, Deralakatte, Mangalore. Sample comprises of 25 cases of clinically and histologically diagnosed oral cancer and 25 normal healthy individuals as control group. The serum was analyzed for ß2-M by enzyme-linked immunosorbent assay. RESULTS: It was observed that there was a significant increase in serum ß2-M levels in oral SCC patients as compared to controls. Circulating levels in serum ß2-M were also elevated significantly among different clinical stages with progressive rise from stage I to stage IV of the disease. CONCLUSION: The evaluation of these markers would be useful in assessing malignant change, increasing accuracy of clinical diagnosis and also in assessing the spread and invasiveness of the cancer of the oral cavity.
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Intussuscepção/diagnóstico por imagem , Doenças do Jejuno/diagnóstico por imagem , Síndrome de Peutz-Jeghers/complicações , Dor Abdominal/etiologia , Humanos , Pólipos Intestinais/patologia , Intussuscepção/etiologia , Intussuscepção/patologia , Doenças do Jejuno/etiologia , Doenças do Jejuno/patologia , Masculino , Pessoa de Meia-Idade , Síndrome de Peutz-Jeghers/diagnóstico , Tomografia Computadorizada por Raios XRESUMO
We present a case of a 35-year-old gentleman with a submandibular duct stone measuring 12 × 6 mm. Considering the literature, most stones are less than 5 mm, and stones more than 10 mm are quite unusual. This gentleman had typical symptoms of chronic sialadenitis, who was clinically diagnosed to have sialolithiasis, which was later confirmed by imaging studies. He was operated upon to remove the stone along with the submandibular gland. The term sialolithiasis is derived from the Greek words sialon (saliva) and lithos (stone), and the Latin -iasis meaning "process" or "morbid condition". Sialolithiasis affects the submandibular gland in 80-90% of cases because of the curved course of submandibular duct and the secretions being more mucous. Pain is the most common presenting feature during mastication and surgical removal of the sialolithiasis is the treatment of choice. The incision depends on the location of the stone in the duct.
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Scabbard is the sheath used for covering swords, knives or other large blades. A scabbard trachea is called so because of its resemblance of shape (Fig. 1) caused by lateral compression usually by thyroid enlargement. Here we present such a case depicting the radiological findings of a scabbard trachea.
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One potent lactic acid bacterial strain C14 with strong antifungal activity was isolated from homemade curd. Based on morphological as well as biochemical characters and 16S rDNA sequence homology the strain was identified as Lactobacillus fermentum. It displayed a wide antimicrobial spectrum against both Gram-positive and Gram-negative pathogenic bacteria, and also against number of food spoilage, plant and human pathogenic fungi. The cell free supernatant (CFS) of the strain C14 was also effective against the fungi tested. Inhibition of radial growth of Penicillium digitatum, Trichophyton rubrum and Mucor sp. was noticed in the presence of CFS of C14 even at low concentration (1%). More than 94.3 ± 1.6% and 91.5 ± 2.2% inhibition of conidial germination of P. digitatum and Mucor sp. were noticed in the presence of 10-fold-concentrated CFS of C14. Massive deformation of the fungal mycelia was observed by SEM studies, and losses of cellular proteins and DNA are also evident upon its treatment with C14. HPLC analysis revealed the presence of phenyl lactic acid, lactic acid along with some unidentified compounds in the antifungal extract. Challenge experiment showed immense potential of the strain C14 in preventing the spoilage of bread samples caused by Mucor sp. and Bacillus subtilis. The bread samples remained fresh upto 25 days even after inoculation with Mucor sp. (3.7 × 104 spores /ml) and B. subtilis (4.6 × 104 CFU /ml). Along with the antifungal properties, the isolated lactic acid bacterial strain also showed very good antioxidant activities. Unchanged level of liver enzymes serum glutamic pyruvic transaminase and serum glutamic oxaloacetic transaminase in albino mice upon feeding with C14 also suggested non-toxic nature of the bacterial isolate.
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Anti-Infecciosos/farmacologia , Antibiose , Conservantes de Alimentos/farmacologia , Lactatos/farmacologia , Ácido Láctico/farmacologia , Limosilactobacillus fermentum/química , Leite/microbiologia , Alanina Transaminase/metabolismo , Animais , Anti-Infecciosos/isolamento & purificação , Aspartato Aminotransferases/sangue , Pão , Fermentação , Conservantes de Alimentos/isolamento & purificação , Armazenamento de Alimentos/métodos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/crescimento & desenvolvimento , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/crescimento & desenvolvimento , Humanos , Lactatos/isolamento & purificação , Ácido Láctico/isolamento & purificação , Limosilactobacillus fermentum/isolamento & purificação , Masculino , Camundongos , Mucor/efeitos dos fármacos , Mucor/crescimento & desenvolvimento , Micélio/efeitos dos fármacos , Micélio/crescimento & desenvolvimento , Penicillium/efeitos dos fármacos , Penicillium/crescimento & desenvolvimento , Trichophyton/efeitos dos fármacos , Trichophyton/crescimento & desenvolvimentoRESUMO
Early detection of hepatocellular carcinoma (HCC) leads to improved survival; however, current early detection strategies for HCC surveillance are ineffective. Thus, there has been interest in developing biomarkers to aid in the early detection HCC. In this review, we discuss the five phases of biomarker discovery that are necessary for clinical implementation. We also describe the most promising investigational biomarkers and their phase of discovery. We review several promising technologies for the early detection of HCC, including miRNA, metabolomics and proteomics. Promisingly, there are samples from multiple longitudinal cohorts of patients with cirrhosis in the USA that are being collected in order to validate candidate biomarkers for HCC. A biomarker-based strategy has the potential to become the primary surveillance method for HCC detection.