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Metformin-associated lactic acidosis:A mini review of pathophysiology,diagnosis and management in critically ill patients

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World Journal of Diabetes 2024年第6期15卷 1178-1186页

作者： kay Choong See Department of Medicine National University HospitalSingapore 119228Singapore

Metformin is a common diabetes drug that may reduce lactate clearance by inhibiting mitochondrial oxidative phosphorylation,leading to metforminassociated lactic acidosis(MALA).As diabetes mellitus is a common chronic metabolic condition found in critically ill patients,pre-existing metformin use can often be found in critically ill patients admitted to the intensive care unit or the high dependency *** aim of this narrative mini review is therefore to update clinicians about MALA,and to provide a practical approach to its diagnosis and *** in critically ill patients may be suspected in a patient who has received metformin and who has a high anion gap metabolic acidosis,and confirmed when lactate exceeds 5 mmol/*** factors include those that reduce renal elimination of metformin(renal impairment from any cause,histamine-2 receptor antagonists,ribociclib)and excessive alcohol consumption(as ethanol oxidation consumes nicotinamide adenine dinucleotides that are also required for lactate metabolism).Treatment of MALA involves immediate cessation of metformin,supportive management,treating other concurrent causes of lactic acidosis like sepsis,and treating any coexisting diabetic *** MALA requires extracorporeal removal of metformin with either intermittent hemodialysis or continuous kidney replacement *** optimal time to restart metformin has not been *** is nonetheless reasonable to first ensure that lactic acidosis has resolved,and then recheck the kidney function post-recovery from critical illness,ensuring that the estimated glomerular filtration rate is 30 mL/min/1.73 m^(2) or better before restarting metformin.

关键词： Acid-base equilibrium Biguanides Oxidative phosphorylation Pyruvic acid Renal replacement therapy

Clinical and socioeconomic determinants of survival in biliary tract adenocarcinomas

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1374-1383页

作者： Laura Sahyoun kay Chen Cynthia Tsay George Chen Petr Protiva Department of Gastroenterology and Hepatology Weill Cornell MedicineNew YorkNY 10065United States Gastroenterology Section Jennifer Moreno VA San Diego Healthcare SystemSan DiegoCA 92161United States Division of Gastroenterology Department of MedicineUniversity of California San DiegoLa JollaCA 92093United States Department of Gastroenterology and Hepatology John Hopkins HospitalBaltimoreMD 21287United States Department of Digestive Diseases Yale New Haven HospitalNew HavenCT 06520United States Department of Gastroenterology VA Connecticut Health Care SystemWest HavenCT 06516United States

BACKGROUND Despite advances in detection and treatments,biliary tract cancers continue to have poor survival ***,there is limited data investigating the significance of socioeconomic status,race/ethnicity,and environmental factors in biliary tract cancer *** from the Surveillance,Epidemiology,and End Results database for biliary and gallbladder adenocarcinomas were extracted from 1975 to ***-conomic data included smoking,poverty level,education,adjusted household income,and percentage of foreign-born persons and urban *** was calculated with Cox proportional hazards models for death in the 5-year period following *** Our study included 15883 gallbladder,11466 intrahepatic biliary,12869 extrahepatic biliary and 7268 ampulla of Vater adenocarcinoma *** analyzing county-specific demographics,patients from counties with higher incomes were associated with higher survival rates[hazard ratio(HR)=0.97,P<0.05].Similarly,counties with a higher percentage of patients with a college level education and counties with a higher urban population had higher 5-year survival rates(HR=0.96,P=0.002 and HR=0.97,P=0.004,respectively).CONCLUSION Worse survival outcomes were observed in lower income counties while higher income and education level were associated with higher 5-year overall survival among gallbladder and biliary malignancies.

关键词： Biliary tract cancers Survival Outcomes research Socioeconomic factors Healthcare disparities

Orchard Sports Injury and Illness Classification System (OSIICS) Version 15

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Journal of Sport and Health Science 2024年第4期13卷 599-604页

作者： John W.Orchard Ebonie Rio kay M.Crossley Jessica J.Orchard Margo Mountjoy School of Public Health University of SydneySydneyNSW 2006Australia La Trobe Sport and Exercise Medicine Research Centre La Trobe UniversityMelbourneVIC 3083Australia Department of Family Medicine McMaster UniversityHamilton L8S 4L8Canada

Background:Sports medicine(injury and illnesses)requires distinct coding systems because the International Classification of Diseases is insuf-ficient for sports medicine *** Orchard Sports Injury and Illness Classification System(OSIICS)is one of two sports medicine coding systems recommended by the International Olympic *** updates of coding systems are ***:For Version 15,updates for mental health conditions in athletes,sports cardiology,concussion sub-types,infectious diseases,and skin and eye conditions were considered particularly ***:Recommended codes were added from a recent International Olympic Committee consensus statement on mental health conditions in *** landmark sports cardiology papers were used to update a more comprehensive list of sports cardiology *** union protocols on head injury assessment were used to create additional concussion ***:It is planned that OSIICS Version 15 will be translated into multiple new languages in a timely fashion to facilitate international *** large number of recently published sport-specific and discipline-specific consensus statements on athlete surveillance warrant regular updating of OSIICS.

关键词： Sports cardiology Dermatology Eye injuries Concussion Infectious diseases Sports injury classification

A Multi-Channel CMOS Analog Front-End Interface IC with 157.8 d B Current Detection Dynamic Range

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Chinese Journal of Electronics 2024年第2期33卷 393-402页

作者： Kunyu WANG Wenjing XU Chengbin ZHANG Yanjun YANG Man-kay LAW Li ZHOU Jie CHEN Ming CHEN Institute of Microelectronics of the Chinese Academy of Science University of Chinese Academy of Sciences Zunyi Normal University Institute of Microelectronics and Dept.of ECE FST University of Macau

A high dynamic range and low-noise CMOS(complementary metal-oxide-semiconductor transistor)front-end interface integrated circuit(IC) with multi-channel detection is presented in this paper. Two different current detection channels, composed of a trans-impedance amplifier(TIA) and an integrator-differentiator TIA, are used to boost the current detection range. A capacitance-coupled instrument amplifier(CCIA) is also included to realize high precision voltage detection. A fourth-order sigma-delta modulator using a second-order loop filter and a second-order noise shaping integral quantizer is adopted to realize effective number of bits above 16 bits. The presented interface IC is implemented in 0.18-μm CMOS process with supply voltage of 3.3 V, and a proto-type electrochemical sensor platform with miniaturized sensor array is developed to verify the functionality of the interface IC. Measurement results indicate that the designed interface IC achieves 157.8 d B current detection dynamic range, and the measured input-referred current noise and voltage noise floor are 1.04 p A and 58.4 n V within 10 k Hz integration bandwidths,respectively.

关键词： Integrated circuits Sigma-delta modulation Semiconductor device measurement Voltage measurement Current measurement Noise Bandwidth

Diagnosis and management of severe pulmonary and extrapulmonary tuberculosis in critically ill patients:A mini review for clinicians

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World Journal of Critical Care Medicine 2024年第2期13卷 106-115页

作者： Dominic Ti Ming Tan kay Choong See Department of Medicine National University HospitalSingapore 119228Singapore

Among critically ill patients,severe pulmonary and extrapulmonary tuberculosis has high morbidity and ***,it is a diagnostic challenge given its nonspecific clinical symptoms and signs in early stages of the *** addition,management of severe pulmonary and extrapulmonary tuberculosis is complicated given the high risk of drug-drug interactions,drug-disease interactions,and adverse drug *** help clinicians acquire an up-to-date approach to severe tuberculosis,this paper will provide a narrative review of contemporary diagnosis and management of severe pulmonary and extrapulmonary tuberculosis in critically ill patients.

关键词： Tuberculosis Severe tuberculosis Mycobaterium tuberculosis Critical care Intensive care Diagnosis of tuberculosis Management of tuberculosis

EZH2 inhibitors promote β-like cell regeneration in young and adult type 1 diabetes donors

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Signal Transduction and Targeted Therapy 2024年第2期9卷 679-692页

作者： Keith Al-Hasani Safiya Naina Marikar Harikrishnan Kaipananickal Scott Maxwell Jun Okabe Ishant Khurana Thomas Karagiannis Julia J.Liang Lina Mariana Thomas Loudovaris Thomas kay Assam El-Osta Epigenetics in Human Health and Disease Program Baker Heart and Diabetes Institute75 Commercial RoadMelbourne 3004 VICAustralia Department of Diabetes Central Clinical SchoolMonash UniversityMelbourne 3004 VICAustralia Epigenetics in Human Health and Disease Laboratory Central Clinical SchoolMonash UniversityMelbourne 3004 VICAustralia School of Science STEM CollegeRMIT UniversityMelbourne 3001 VICAustralia Immunology and Diabetes Unit St Vincent’s Institute of Medical ResearchFitzroy 3065 VICAustralia Department of Medicine and Therapeutics The Chinese University of Hong KongSha TinHong Kong SAR Hong Kong Institute of Diabetes and Obesity Prince of Wales HospitalThe Chinese University of Hong Kong3/F Lui Che Woo Clinical Sciences Building30-32-Ngan Shing StreetSha TinHong Kong SAR Li Ka Shing Institute of Health Sciences The Chinese University of Hong KongSha TinHong Kong SAR Biomedical Laboratory Science Department of TechnologyFaculty of HealthUniversity College CopenhagenCopenhagenDenmark

β-cells are a type of endocrine cell found in pancreatic islets that synthesize,store and release *** type 1 diabetes(T1D),T-cells of the immune system selectively destroy the insulin-producingβ-*** of these cells leads to a lifelong dependence on exogenous insulin administration for ***,there is an urgent need to identify novel therapies that stimulateβ-cell growth and induceβ-cell *** and others have shown that pancreatic ductal progenitor cells are a promising source for regeneratingβ-cells for T1D owing to their inherent differentiation *** transcriptional suppression is refractory to exocrine reaction and tightly controls the regenerative potential by the EZH2 *** the present study,we show that transient stimulation of exocrine cells,derived from juvenile and adult T1D donors to the FDAapproved EZH2 inhibitors GSK126 and Tazemetostat(Taz)influence a phenotypic shift towards aβ-like cell *** transition from repressed to permissive chromatin states are dependent on bivalent H3K27me3 and H3K4me3 chromatin *** EZH2 is fundamental toβ-cell regenerative *** pancreatic ductal cells exhibit insulin production and secretion in response to a physiological glucose challenge ex *** pre-clinical studies underscore the potential of small molecule inhibitors as novel modulators of ductal progenitor differentiation and a promising new approach for the restoration ofβ-like cell function.

关键词： EZH2 struction inhibitors

Hepatic angiotensin-converting enzyme 2 expression in metabolic dysfunction-associated steatotic liver disease and in patients with fatal COVID-19

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World Journal of Gastroenterology 2024年第31期30卷 3705-3716页

作者： Angus K Jacobs Steven D Morley kay Samuel Katie Morgan Lyndsey Boswell Timothy J Kendall David A Dorward Jonathan A Fallowfield Peter C Hayes John N Plevris Hepatology Laboratory University of EdinburghEdinburgh EH164SBUnited Kingdom Scottish National Blood Transfusion Service Jack Copland CentreEdinburgh EH144BEUnited Kingdom Institute for Regeneration and Repair University of EdinburghEdinburgh EH164UUUnited Kingdom Edinburgh Pathology University of EdinburghEdinburgh EH164SBUnited Kingdom

BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD),characterised by hepatic lipid accumulation,causes inflammation and oxidative stress accompanied by cell damage and *** injury(LI)is also frequently reported in patients hospitalised with coronavirus disease 2019(COVID-19),while preexisting MASLD increases the risk of LI and the development of COVID-19-associated *** of injury at the cellular level remain unclear,but it may be significant that severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)which causes COVID-19,uses angiotensin-converting expression enzyme 2(ACE2),a key regulator of the‘anti-inflammatory’arm of the renin-angiotensin system,for viral attachment and host cell *** To determine if hepatic ACE2 levels are altered during progression of MASLD and in patients who died with severe *** ACE2 protein levels and localisation,and histological fibrosis and lipid droplet accumulation as markers of MASLD were determined in formalin-fixed liver tissue sections across the MASLD pathological spectrum(isolated hepatocellular steatosis,metabolic dysfunction-associated steatohepatitis(MASH)+/-fibrosis,end-stage cirrhosis)and in post-mortem tissues from patients who had died with severe COVID-19,using ACE2 immunohistochemistry and haematoxylin and eosin and picrosirius red staining of total collagen and lipid droplet areas,followed by quantification using machine learning-based image pixel *** ACE2 staining is primarily intracellular and concentrated in the cytoplasm of centrilobular hepatocytes and apical membranes of bile duct ***,ACE2 protein levels are elevated in non-fibrotic MASH compared to healthy controls but not in the progression to MASH with fibrosis and in ***2 protein levels and histological fibrosis are not associated,but ACE2 and liver lipid droplet content are significantly correlated across the MASLD *** A

关键词： Metabolic dysfunction-associated steatotic liver disease Angiotensin-converting enzyme 2 Immunohistochemistry COVID-19 COVID-19-associated cholangiopathy

Quantitative and qualitative subgenomic RNA profiles of SARS-CoV-2 in respiratory samples: A comparison between Omicron BA.2 and non-VOC-D614G

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Virologica Sinica 2024年第2期39卷 218-227页

作者： Zigui Chen Rita Way Yin Ng Grace Lui Lowell Ling Agnes S.Y.Leung Chit Chow Siaw Shi Boon Wendy C.S.Ho Maggie Haitian Wang Renee Wan Yi Chan Albert Martin Li David Shu Cheong Hui Paul kay Sheung Chan Department of Microbiology Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Medicine and Therapeutics Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Anaesthesia and Intensive Care Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Paediatrics Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Anatomical and Cellular Pathology Faculty of MedicineThe Chinese University of Hong KongHong KongChina Jockey Club School of Public Health and Primary Care Faculty of MedicineThe Chinese University of Hong KongHong KongChina Stanley Ho Centre for Emerging Infectious Diseases Faculty of MedicineThe Chinese University of Hong KongHong KongChina

The SARS-CoV-2 Omicron variants are notorious for their transmissibility,but little is known about their subgenomic RNA(sgRNA)*** study applied RNA-seq to delineate the quantitative and qualitative profiles of canonical sgRNA of 118 respiratory samples collected from patients infected with Omicron BA.2 and compared with 338 patients infected with non-variant of concern(non-VOC)-D614G.A unique characteristic profile depicted by the relative abundance of 9 canonical sgRNAs was reproduced by both BA.2 and non-VOCD614G regardless of host gender,age and presence of ***,such profile was lost in samples with low viral load,suggesting a potential application of sgRNA pattern to indicate viral activity of individual patient at a specific time point.A characteristic qualitative profile of canonical sgRNAs was also reproduced by both BA.2 and *** presence of a full set of canonical sgRNAs carried a coherent correlation with crude viral load(AUC¼0.91,95%CI 0.88–0.94),and sgRNA ORF7b was identified to be the best surrogate marker allowing feasible routine application in characterizing the infection status of individual *** potentials in using sgRNA as a target for vaccine and antiviral development are worth pursuing.

关键词： Coronavirus SARS-CoV-2 Omicron BA.2 Non-VOC-D614G RNA-seq Subgenomic RNA(sgRNA)

Prevalence and risk factors for impaired renal function among Asian patients with nonalcoholic fatty liver disease

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Hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 241-248页

作者： Chao Sun George Boon-Bee Goh Wan-Cheng Chow Wah-Kheong Chan Grace Lai-Hung Wong Wai-kay Seto Yi-Hsiang Huang Han-Chieh Lin I-Cheng Lee Hye Won Lee Seung Up Kim Vincent Wai-Sun Wong Jian-Gao Fan Center for Fatty Liver Disease Department of GastroenterologyXinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai Key Lab of Pediatric Gastroenterology and NutritionShanghai 200092China Department of Gastroenterology&Hepatology Singapore General HospitalSingaporeSingapore Gastroenterology and Hepatology Unit Department of MedicineFaculty of MedicineUniversity of MalayaKuala LumpurMalaysia Department of Medicine and Therapeutics and State Key Laboratory of Digestive Disease The Chinese University of Hong KongHong KongChina Department of Medicine The University of Hong KongHong KongChina Institute of Clinical Medicine National Yang Ming Chiao Tung University School of MedicineTaipeiTaiwanChina Division of Gastroenterology and Hepatology Taipei Veterans General HospitalTaipeiTaiwanChina Faculty of Medicine National Yang Ming Chiao Tung University School of MedicineTaipeiTaiwanChina Department of Internal Medicine Yonsei University College of MedicineSeoulKorea

Background:Nonalcoholic fatty liver disease(NAFLD)is associated with impaired renal function,and both diseases often occur alongside other metabolic ***,the prevalence and risk factors for impaired renal function in patients with NAFLD remain *** objective of this study was to identify the prevalence and risk factors for renal impairment in NAFLD ***:All adults aged 18-70 years with ultrasound-diagnosed NAFLD and transient elastography examination from eight Asian centers were enrolled in this prospective *** fibrosis and cirrhosis were assessed by FibroScan-aspartate aminotransferase(FAST),Agile 3+and Agile 4 *** renal function and chronic kidney disease(CKD)were defined by an estimated glomerular filtration rate(eGFR)with value of<90 mL/min/1.73 m^(2) and<60 mL/min/1.73 m^(2),respectively,as estimated by the CKD-Epidemiology Collaboration(CKD-EPI)***:Among 529 included NAFLD patients,the prevalence rates of impaired renal function and CKD were 37.4%and 4.9%,*** multivariate analysis,a moderate-high risk of advanced liver fibrosis and cirrhosis according to Agile 3+and Agile 4 scores were independent risk factors for CKD(P<0.05).Furthermore,increased fasting plasma glucose(FPG)and blood pressure were significantly associated with impaired renal function after controlling for the other components of metabolic syndrome(P<0.05).Compared with patients with normoglycemia,those with prediabetes[FPG≥5.6 mmol/L or hemoglobin A1c(HbA1c)≥5.7%]were more likely to have impaired renal function(P<0.05).Conclusions:Agile 3+and Agile 4 are reliable for identifying NAFLD patients with high risk of *** glycemic control in the prediabetic stage might have a potential renoprotective role in these patients.

关键词： Nonalcoholic fatty liver disease Impaired renal function Agile 3+ Agile 4 Metabolic syndrome