Corneal neuromas,also termed microneuromas,refer to microscopic,irregula rly-shaped enlargements of terminal subbasal nerve endings at sites of nerve damage or injury.The formation of corneal neuromas results from dam...Corneal neuromas,also termed microneuromas,refer to microscopic,irregula rly-shaped enlargements of terminal subbasal nerve endings at sites of nerve damage or injury.The formation of corneal neuromas results from damage to corneal nerves,such as following corneal pathology or corneal or intraocular surge ries.Initially,denervated areas of sensory nerve fibers become invaded by sprouts of intact sensory nerve fibers,and later injured axons regenerate and new sprouts called neuromas develop.In recent years,analysis of corneal nerve abnormalities including corneal neuromas which can be identified using in vivo confocal microscopy,a non-invasive imaging technique with microscopic resolution,has been used to evaluate corneal neuropathy and ocular surface dysfunction.Corneal neuromas have been shown to be associated with clinical symptoms of discomfort and dryness of eyes,and are a promising surrogate biomarker for ocular surface diseases,such as neuropathic corneal pain,dry eye disease,diabetic corneal neuropathy,neurotrophic keratopathy,Sjogren's syndrome,bullous keratopathy,post-refra ctive surgery,and others.In this review,we have summarized the current literature on the association between these ocular surface diseases and the presentation of corneal microneuromas,as well as elaborated on their pathogenesis,visualization via in vivo confocal microscopy,and utility in monitoring treatment efficacy.As current quantitative analysis on neuromas mainly relies on manual annotation and quantification,which is user-dependent and labor-intensive,future direction includes the development of artificial intelligence software to identify and quantify these potential imaging biomarkers in a more automated and sensitive manner,allowing it to be applied in clinical settings more efficiently.Combining imaging and molecular biomarkers may also help elucidate the associations between corneal neuromas and ocular surface diseases.展开更多
The interaction between metabolic dysfunction and inflammation is central to the development of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease.Obesity-related conditions like type 2 d...The interaction between metabolic dysfunction and inflammation is central to the development of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease.Obesity-related conditions like type 2 diabetes and non-alcoholic fatty liver disease exacerbate this relationship.Peripheral lipid accumulation,particularly in the liver,initiates a cascade of inflammatory processes that extend to the brain,influencing critical metabolic regulatory regions.Ceramide and palmitate,key lipid components,along with lipid transporters lipocalin-2 and apolipoprotein E,contribute to neuroinflammation by disrupting blood–brain barrier integrity and promoting gliosis.Peripheral insulin resistance further exacerbates brain insulin resistance and neuroinflammation.Preclinical interventions targeting peripheral lipid metabolism and insulin signaling pathways have shown promise in reducing neuroinflammation in animal models.However,translating these findings to clinical practice requires further investigation into human subjects.In conclusion,metabolic dysfunction,peripheral inflammation,and insulin resistance are integral to neuroinflammation and neurodegeneration.Understanding these complex mechanisms holds potential for identifying novel therapeutic targets and improving outcomes for neurodegenerative diseases.展开更多
Magnesium(Mg)and its alloys have recently gained increasing attention in the biomedical field as promising biodegradable materials with harmless degradation products.Magnesium-based alloys have a wide range of biomedi...Magnesium(Mg)and its alloys have recently gained increasing attention in the biomedical field as promising biodegradable materials with harmless degradation products.Magnesium-based alloys have a wide range of biomedical applications because of their outstanding biocompatibility and unique mechanical properties.Widespread use of Mg-based biomedical devices eliminates the need for post-healing biomaterial removal surgery and minimizes the negative consequences of the implantation of permanent biomaterials,including stress shielding and undesired metal ion release in the body.This paper provides a literature review on the properties and manufacturing methods of Mgbased alloys for biomedical applications,including orthopedic implants,cardiovascular applications,surgical wires and staplers,and antitumor activities.Each application of Mg-based biomaterials is investigated from a biological perspective,including matching functional properties,biocompatibility,host tissue responses,and anti-microbial strategies,along with potential additive manufacturing technologies for these applications.Finally,an outlook is presented to provide recommendations for Mg-based biomaterials in the future.展开更多
BACKGROUND Research on long-term survival after resection of giant(≥10 cm)and non-giant hepatocellular carcinoma(HCC)(<10 cm)has produced conflicting results.AIM This study aimed to investigate whether oncological...BACKGROUND Research on long-term survival after resection of giant(≥10 cm)and non-giant hepatocellular carcinoma(HCC)(<10 cm)has produced conflicting results.AIM This study aimed to investigate whether oncological outcomes and safety profiles of resection differ between giant and non-giant HCC.METHODS PubMed,MEDLINE,EMBASE,and Cochrane databases were searched.Studies designed to investigate the outcomes of giant vs non-giant HCC were included.The primary endpoints were overall survival(OS)and disease-free survival(DFS).The secondary endpoints were postoperative complications and mortality rates.All studies were assessed for bias using the Newcastle–Ottawa Scale.RESULTS 24 retrospective cohort studies involving 23747 patients(giant=3326;non-giant=20421)who underwent HCC resection were included.OS was reported in 24 studies,DFS in 17 studies,30-d mortality rate in 18 studies,postoperative complications in 15 studies,and post-hepatectomy liver failure(PHLF)in six studies.The HR was significantly lower for non-giant HCC in both OS(HR 0.53,95%CI:0.50-0.55,P<0.001)and DFS(HR 0.62,95%CI:0.58-0.84,P<0.001).No significant difference was found for 30-d mortality rate(OR 0.73,95%CI:0.50-1.08,P=0.116),postoperative complications(OR 0.81,95%CI:0.62-1.06,P=0.140),and PHLF(OR 0.81,95%CI:0.62-1.06,P=0.140).CONCLUSION Resection of giant HCC is associated with poorer long-term outcomes.The safety profile of resection was similar in both groups;however,this may have been confounded by reporting bias.HCC staging systems should account for the size differences.展开更多
BACKGROUND Acute pancreatitis(AP)is a disease spectrum ranging from mild to severe disease.During the coronavirus disease 2019(COVID-19)pandemic,numerous reports of AP have been published,with most authors concluding ...BACKGROUND Acute pancreatitis(AP)is a disease spectrum ranging from mild to severe disease.During the coronavirus disease 2019(COVID-19)pandemic,numerous reports of AP have been published,with most authors concluding a causal relationship between COVID-19 and AP.Retrospective case reports or small case series are unable to accurately determine the cause-effect relationship between COVID-19 and AP.AIM To establish whether COVID-19 is a cause of AP using the modified Naranjo scoring system.METHODS A systematic review was conducted on PubMed,World of Science and Embase for articles reporting COVID-19 and AP from inception to August 2021.Exclusion criteria were cases of AP which were not reported to be due to COVID-19 infection,age<18 years old,review articles and retrospective cohort studies.The original 10-item Naranjo scoring system(total score 13)was devised to approximate the likelihood of a clinical presentation to be secondary to an adverse drug reaction.We modified the original scoring system into a 8-item modified Naranjo scoring system(total score 9)to determine the cause-effect relationship between COVID-19 and AP.A cumulative score was decided for each case presented in the included articles.Interpretation of the modified Naranjo scoring system is as follows:≤3:Doubtful,4-6:Possible,≥7:Probable cause.RESULTS The initial search resulted in 909 articles,with 740 articles after removal of duplicates.A total of 67 articles were included in the final analysis,with 76 patients which had AP reported to be due to COVID-19.The mean age was 47.8(range 18-94)years.Majority of patients(73.3%)had≤7 d between onset of COVID-19 infection and diagnosis of AP.There were only 45(59.2%)patients who had adequate investigations to rule out common aetiologies(gallstones,choledocholithiasis,alcohol,hypertriglyceridemia,hypercalcemia and trauma)of AP.Immunoglobulin G4 testing was conducted in 9(13.5%)patients to rule out autoimmune AP.Only 5(6.6%)patients underwent endoscopic ultrasound and/or magnetic resonance cholangiopancreatogram to rule out occult microlithiasis,pancreatic malignancy and pancreas divisum.None of the patients had other recently diagnosed viral infections apart from COVID-19 infection,or underwent genetic testing to rule out hereditary AP.There were 32(42.1%),39(51.3%)and 5(6.6%)patients with doubtful,possible,and probable cause-effect relationship respectively between COVID-19 and AP.CONCLUSION Current evidence is weak to establish a strong link between COVID-19 and AP.Investigations should be performed to rule out other causes of AP before establishing COVID-19 as an aetiology.展开更多
BACKGROUND Gastric cancer is one of the leading causes of cancer burden and mortality,often resulting in peritoneal metastasis in advanced stages with negative survival outcomes.Staging laparoscopy has become standard...BACKGROUND Gastric cancer is one of the leading causes of cancer burden and mortality,often resulting in peritoneal metastasis in advanced stages with negative survival outcomes.Staging laparoscopy has become standard practice for suspected cases before a definitive gastrectomy or palliation.This systematic review aims to compare the efficacy of other diagnostic modalities instead of staging laparoscopy as the alternatives are able to reduce cost and invasive staging procedures.Recently,a radiomic model based on computed tomography and positron emission tomography(PET)has also emerged as another method to predict peritoneal metastasis.AIM To determine if the efficacy of computed tomography,magnetic resonance imaging and PET is comparable with staging laparoscopy.METHODS Articles comparing computed tomography,PET,magnetic resonance imaging,and radiomic models based on computed tomography and PET to staging laparoscopies were filtered out from the Cochrane Library,EMBASE,PubMed,Web of Science,and Reference Citations Analysis(https://www.referencecitationanalysis.com/).In the search for studies comparing computed tomography(CT)to staging laparoscopy,five retrospective studies and three prospective studies were found.Similarly,five retrospective studies and two prospective studies were also included for papers comparing CT to PET scans.Only one retrospective study and one prospective study were found to be suitable for papers comparing CT to magnetic resonance imaging scans.RESULTS Staging laparoscopy outperformed computed tomography in all measured aspects,namely sensitivity,specificity,positive predictive value and negative predictive value.Magnetic resonance imaging and PET produced mixed results,with the former shown to be only marginally better than computed tomography.CT performed slightly better than PET in most measured domains,except in specificity and true negative rates.We speculate that this may be due to the limited F-fluorodeoxyglucose uptake in small peritoneal metastases and in linitis plastica.Radiomic modelling,in its current state,shows promise as an alternative for predicting peritoneal metastases.With further research,deep learning and radiomic modelling can be refined and potentially applied as a preoperative diagnostic tool to reduce the need for invasive staging laparoscopy.CONCLUSION Staging laparoscopy was superior in all measured aspects.However,associated risks and costs must be considered.Refinements in radiomic modelling are necessary to establish it as a reliable screening technique.展开更多
performed independently by authors(Yap KY,Chi H,Ng S)identified 50 studies for full-text evaluation.Finally,12 prospective RCTs and 4 non-randomised studies(1 non-randomised trial and 3 observational studies)were incl...performed independently by authors(Yap KY,Chi H,Ng S)identified 50 studies for full-text evaluation.Finally,12 prospective RCTs and 4 non-randomised studies(1 non-randomised trial and 3 observational studies)were included.A detailed PRISMA diagram is shown in Figure 1.The studies included were assessed for risk of bias,with a summary of the assessment shown in Figure 2 and Table 1 for trials and non-interventional studies,respectively.The PRISMA checklist is appended in Supplementary Figure 1.展开更多
Neuronal necroptosis-an emerging form of regulated cell death associated with neuroinflammatory signaling:Alzheimer’s disease(AD)is characterized by the presence of extracellular amyloid-β(Aβ)plaques and intracellu...Neuronal necroptosis-an emerging form of regulated cell death associated with neuroinflammatory signaling:Alzheimer’s disease(AD)is characterized by the presence of extracellular amyloid-β(Aβ)plaques and intracellular tau neurofibrillary tangles as well as progressive neuronal loss.Recent evidence has suggested that prolonged neuroinflammation with increased levels of cytokines,arising from neuronal injury,innate immune responses from glial cells,and peripheral inflammation,leads to neuronal death and AD progression.展开更多
A pancreatic pseudocyst is defined as an encapsulated fluid collection with a welldefined inflammatory wall with minimal or no necrosis.The diagnosis cannot be made prior to 4 wk after the onset of pancreatitis.The cl...A pancreatic pseudocyst is defined as an encapsulated fluid collection with a welldefined inflammatory wall with minimal or no necrosis.The diagnosis cannot be made prior to 4 wk after the onset of pancreatitis.The clinical presentation is often nonspecific,with abdominal pain being the most common symptom.If a diagnosis is suspected,contrast-enhanced computed tomography and/or magnetic resonance imaging are performed to confirm the diagnosis and assess the characteristics of the pseudocyst.Endoscopic ultrasound with cyst fluid analysis can be performed in cases of diagnostic uncertainty.Pseudocyst of the pancreas can lead to complications such as hemorrhage,infection,and rupture.The management of pancreatic pseudocysts depends on the presence of symptoms and the development of complications,such as biliary or gastric outlet obstruction.Management options include endoscopic or surgical drainage.The aim of this review was to summarize the current literature on pancreatic pseudocysts and discuss the evolution of the definitions,diagnosis,and management of this condition.展开更多
Randomized controlled trials(RCTs)have long been recognized as the gold standard for establishing causal relationships in clinical research.Despite that,various limitations of RCTs prevent its widespread implementatio...Randomized controlled trials(RCTs)have long been recognized as the gold standard for establishing causal relationships in clinical research.Despite that,various limitations of RCTs prevent its widespread implementation,ranging from the ethicality of withholding potentially-lifesaving treatment from a group to relatively poor external validity due to stringent inclusion criteria,amongst others.However,with the introduction of propensity score matching(PSM)as a retrospective statistical tool,new frontiers in establishing causation in clinical research were opened up.PSM predicts treatment effects using observational data from existing sources such as registries or electronic health records,to create a matched sample of participants who received or did not receive the intervention based on their propensity scores,which takes into account characteristics such as age,gender and comorbidities.Given its retrospective nature and its use of observational data from existing sources,PSM circumvents the aforementioned ethical issues faced by RCTs.Majority of RCTs exclude elderly,pregnant women and young children;thus,evidence of therapy efficacy is rarely proven by robust clinical research for this population.On the other hand,by matching study patient characteristics to that of the population of interest,including the elderly,pregnant women and young children,PSM allows for generalization of results to the wider population and hence greatly increases the external validity.Instead of replacing RCTs with PSM,the synergistic integration of PSM into RCTs stands to provide better research outcomes with both methods complementing each other.For example,in an RCT investigating the impact of mannitol on outcomes among participants of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial,the baseline characteristics of comorbidities and current medications between treatment and control arms were significantly different despite the randomization protocol.Therefore,PSM was incorporated in its analysis to create samples from the treatment and control arms that were matched in terms of these baseline characteristics,thus providing a fairer comparison for the impact of mannitol.This literature review reports the applications,advantages,and considerations of using PSM with RCTs,illustrating its utility in refining randomization,improving external validity,and accounting for non-compliance to protocol.Future research should consider integrating the use of PSM in RCTs to better generalize outcomes to target populations for clinical practice and thereby benefit a wider range of patients,while maintaining the robustness of randomization offered by RCTs.展开更多
Liver transplantation represents a pivotal intervention in the management of end-stage liver disease,offering a lifeline to countless patients.Despite significant strides in surgical techniques and organ procurement,e...Liver transplantation represents a pivotal intervention in the management of end-stage liver disease,offering a lifeline to countless patients.Despite significant strides in surgical techniques and organ procurement,ethical dilemmas and de-bates continue to underscore this life-saving procedure.Navigating the ethical terrain surrounding this complex procedure is hence paramount.Dissecting the nuances of ethical principles of justice,autonomy and beneficence that underpin transplant protocols worldwide,we explore the modern challenges that plaques the world of liver transplantation.We investigate the ethical dimensions of organ transplantation,focusing on allocation,emerging technologies,and decision-making processes.PubMed,Scopus,Web of Science,Embase and Central were searched from database inception to February 29,2024 using the following key-words:“liver transplant”,“transplantation”,“liver donation”,“liver recipient”,“organ donation”and“ethics”.Information from relevant articles surrounding ethical discussions in the realm of liver transplantation,especially with regards to organ recipients and allocation,organ donation,transplant tourism,new age technologies and developments,were extracted.From the definition of death to the long term follow up of organ recipients,liver transplantation has many ethical quandaries.With new transplant techniques,societal acceptance and perceptions also play a pivotal role.Cultural,religious and regional factors including but not limited to beliefs,wealth and accessibility are extremely influential in public at-titudes towards donation,xenotransplantation,stem cell research,and adopting artificial intelligence.Understanding and addressing these perspectives whilst upholding bioethical principles is essential to ensure just distribution and fair allocation of resources.Robust regulatory oversight for ethical sourcing of organs,ensuring good patient selection and transplant techniques,and high-quality long-term surveillance to mitigate risks is essential.Efforts to promote equitable access to transplantation as well as prioritizing patients with true needs are essential to address disparities.In conclusion,liver transplantation is often the beacon of hope for individuals suffering from end-stage liver disease and improves quality of life.The ethics related to transplantation are complex and multifaceted,considering not just the donor and the recipient,but also the society as a whole.展开更多
MiR-219 and miR-338(miR-219/miR-338)are oligodendrocyte-specific microRNAs.The overexpression of these miRs in oligodendrocyte precursor cells promotes their differentiation and maturation into oligodendrocytes,which ...MiR-219 and miR-338(miR-219/miR-338)are oligodendrocyte-specific microRNAs.The overexpression of these miRs in oligodendrocyte precursor cells promotes their differentiation and maturation into oligodendrocytes,which may enhance axonal remyelination after nerve injuries in the central nervous system(CNS).As such,the delivery of miR-219/miR-338 to the CNS to promote oligodendrocyte precursor cell differentiation,maturation and myelination could be a promising approach for nerve repair.However,nerve injuries in the CNS also involve other cell types,such as microglia and astrocytes.Herein,we investigated the effects of miR-219/miR-338 treatment on microglia and astrocytes in vitro and in vivo.We found that miR-219/miR-338 diminished microglial expression of pro-inflammatory cytokines and suppressed astrocyte activation.In addition,we showed that miR-219/miR-338 enhanced oligodendrocyte precursor cell differentiation and maturation in a scratch assay paradigm that re-created a nerve injury condition in vitro.Collectively,our results suggest miR-219/miR-338 as a promising treatment for axonal remyelination in the CNS following nerve injuries.All experimental procedures were approved by the Institutional Animal Care and Use Committee(IACUC),Nanyang Technological University(approval No.A0309 and A0333)on April 27,2016 and October 8,2016.展开更多
BACKGROUND Presence of microvascular invasion(MVI)indicates poorer prognosis postcurative resection of hepatocellular carcinoma(HCC),with an increased chance of tumour recurrence.By present standards,MVI can only be d...BACKGROUND Presence of microvascular invasion(MVI)indicates poorer prognosis postcurative resection of hepatocellular carcinoma(HCC),with an increased chance of tumour recurrence.By present standards,MVI can only be diagnosed postoperatively on histopathology.Texture analysis potentially allows identification of patients who are considered‘high risk’through analysis of pre-operative magnetic resonance imaging(MRI)studies.This will allow for better patient selection,improved individualised therapy(such as extended surgical margins or adjuvant therapy)and pre-operative prognostication.AIM This study aims to evaluate the accuracy of texture analysis on pre-operative MRI in predicting MVI in HCC.METHODS Retrospective review of patients with new cases of HCC who underwent hepatectomy between 2007 and 2015 was performed.Exclusion criteria:No preoperative MRI,significant movement artefacts,loss-to-follow-up,ruptured HCCs,previous hepatectomy and adjuvant therapy.Fifty patients were divided into MVI(n=15)and non-MVI(n=35)groups based on tumour histology.Selected images of the tumour on post-contrast-enhanced T1-weighted MRI were analysed.Both qualitative(performed by radiologists)and quantitative data(performed by software)were obtained.Radiomics texture parameters were extracted based on the largest cross-sectional area of each tumor and analysed using MaZda software.Five separate methods were performed.Methods 1,2 and 3 exclusively made use of features derived from arterial,portovenous and equilibrium phases respectively.Methods 4 and 5 made use of the comparatively significant features to attain optimal performance.RESULTS Method 5 achieved the highest accuracy of 87.8%with sensitivity of 73%and specificity of 94%.CONCLUSION Texture analysis of tumours on pre-operative MRI can predict presence of MVI in HCC with accuracies of up to 87.8%and can potentially impact clinical management.展开更多
Acute pancreatitis(AP)is a disease spectrum ranging from mild to severe with an unpredictable natural course.Majority of cases(80%)are mild and self-limiting.However,severe AP(SAP)has a mortality risk of up to 30%.Est...Acute pancreatitis(AP)is a disease spectrum ranging from mild to severe with an unpredictable natural course.Majority of cases(80%)are mild and self-limiting.However,severe AP(SAP)has a mortality risk of up to 30%.Establishing aetiology and risk stratification are essential pillars of clinical care.Idiopathic AP is a diagnosis of exclusion which should only be used after extended investigations fail to identify a cause.Tenets of management of mild AP include pain control and management of aetiology to prevent recurrence.In SAP,patients should be resuscitated with goal-directed fluid therapy using crystalloids and admitted to critical care unit.Routine prophylactic antibiotics have limited clinical benefit and should not be given in SAP.Patients able to tolerate oral intake should be given early enteral nutrition rather than nil by mouth or parenteral nutrition.If unable to tolerate per-orally,nasogastric feeding may be attempted and routine post-pyloric feeding has limited evidence of clinical benefit.Endoscopic retrograde cholangiopancreatogram should be selectively performed in patients with biliary obstruction or suspicion of acute cholangitis.Delayed step-up strategy including percutaneous retroperitoneal drainage,endoscopic debridement,or minimal-access necrosectomy are sufficient in most SAP patients.Patients should be monitored for diabetes mellitus and pseudocyst.展开更多
Flaviviruses are positive-sense RNA viruses, and many are important human pathogens. Nonstructural protein 2B and 3 of the flaviviruses(NS2BNS3) form an endoplasmic reticulum(ER) membrane-associated hetero-dimeric com...Flaviviruses are positive-sense RNA viruses, and many are important human pathogens. Nonstructural protein 2B and 3 of the flaviviruses(NS2BNS3) form an endoplasmic reticulum(ER) membrane-associated hetero-dimeric complex through the NS2B transmembrane region. The NS2BNS3 complex is multifunctional. The N-terminal region of NS3, and its cofactor NS2B fold into a protease that is responsible for viral polyprotein processing, and the C-terminal domain of NS3 possesses NTPase/RNA helicase activities and is involved in viral RNA replication and virus particle formation. In addition, NS2BNS3 complex has also been shown to modulate viral pathogenesis and the host immune response. Because of the essential functions that the NS2BNS3 complex plays in the flavivirus life cycle, it is an attractive target for antiviral development. This review focuses on the recent biochemical and structural advances of NS2BNS3 and provides a brief update on the current status of drug development targeting this viral protein complex.展开更多
The interplay between glucose metabolism and that of the two other primary nutrient classes, amino acids and fatty acids is critical for regulated insulin secretion. Mitochondrial metabolism of glucose, amino acid and...The interplay between glucose metabolism and that of the two other primary nutrient classes, amino acids and fatty acids is critical for regulated insulin secretion. Mitochondrial metabolism of glucose, amino acid and fatty acids generates metabolic coupling factors(such as ATP, NADPH, glutamate, long chain acyl-CoA and diacylglycerol) which trigger insulin secretion. The observation of protein induced hypoglycaemia in patients with mutations in GLUD1 gene, encoding the enzyme glutamate dehydrogenase(GDH) and HADH gene, encoding for the enzyme short-chain 3-hydroxyacyl-CoA dehydrogenase has provided new mechanistic insights into the regulation of insulin secretion by amino acid and fatty acid metabolism. Metabolic signals arising from amino acid and fatty acid metabolism converge on the enzyme GDH which integrates both signals from both pathways and controls insulin secretion. Hence GDH seems to play a pivotal role in regulating both amino acid and fatty acid metabolism.展开更多
Phosphate is an essential electrolyte for proper mineralisation of bone,buffering of urine,and diverse cellular actions.Hypophosphatemia(HP)is a clinical spectrum which range from asymptomatic to severe complications ...Phosphate is an essential electrolyte for proper mineralisation of bone,buffering of urine,and diverse cellular actions.Hypophosphatemia(HP)is a clinical spectrum which range from asymptomatic to severe complications such as neuromuscular and pulmonary complications,or even death.Post-hepatectomy HP(PHH)has been reported to be 55.5%-100%.Post-hepatectomy,there is rapid uptake of phosphate and increased mitotic counts to aid in regeneration of residual liver.Concurrently,PHH may be due to increased urinary phosphorous from activation of matrix extracellular phosphoglycoprotein in the injured liver,which decreases phosphate influx into hepatocytes to sustain adenosine triphosphate synthesis.A literature review was performed on Pub Med till January 2022.We included 8 studies which reported on impact of PHH on post-operative outcomes.In patients with diseased liver,PHH was reported to have either beneficial or deleterious effects on post-hepatectomy liver failure(PHLF),morbidity and/or mortality in various cohorts.In living donor hepatectomy,PHLF was higher in PHH.Benefits of correction of PHH with reduced postoperative complications have been shown.Correction of PHH should be done based on extent of PHH.Existing studies were however heterogenous;further studies should be conducted to assess PHH on post-operative outcomes with standardized phosphate replacement regimes.展开更多
Objective To study the effect of changing heart rate on the ocular pulse and optic nerve head deformations with a viscoelastic lamina cribrosa.Methods An FE model of a healthy eye was reconstructed.The choroid was bip...Objective To study the effect of changing heart rate on the ocular pulse and optic nerve head deformations with a viscoelastic lamina cribrosa.Methods An FE model of a healthy eye was reconstructed.The choroid was biphasic and consisted of a solid phase(connective tissues)and a fluid phase(blood).The LC was viscoelastic as characterized by a stress-relaxation test.We applied arterial pressures at 18 entry sites(posterior ciliary arteries)and venous pressures at 4 exit sites(vortex veins).The heart rate was varied from 60 bpm to 120 bpm(increment:20 bpm).We reported the ocular pulse amplitude(OPA),pulse volume,optic nerve head(ONH)deformations and the dynamic modulus of the LC at different heart rates.Results With an increasing heart rate,the OPA decreased by 0.04 mmHg for every 10 bpm increase.The pulse volume also exhibited a linear relationship with heart rate,and decreased by 0.13 L.In addition,the storage modulus and the loss modulus of the LC center increased by 0.014 MPa and 0.04 MPa,respectively for every 10 pm increase in heart rate.Conclusions Our model predicted that the OPA,the pulse volume the ONH deformation decreased at a faster heartrate.We also found that the viscoelastic LC became stiffer with an increasing heart rate.Further studies are required to explore the potential links with the vascular dysregulation and axonal loss in glaucoma.展开更多
BACKGROUND Gallbladder carcinosarcoma is a rare hepatobiliary tumor comprising of both carcinomatous and sarcomatous components.Due to its rarity,the literature with regards to the topic is scarce and currently lackin...BACKGROUND Gallbladder carcinosarcoma is a rare hepatobiliary tumor comprising of both carcinomatous and sarcomatous components.Due to its rarity,the literature with regards to the topic is scarce and currently lacking,spanning less than 100 cases.AIM To summarize the current literature on gallbladder carcinosarcoma.METHODS A literature review was performed on the PubMed database using the keywords“Gallbladder”AND“Carcinosarcoma”from 1970 to 2021.Additionally,similar searches were performed on MEDLINE and Web of Science.RESULTS Risk factors noted include female gender,gallstones and chronic cholecystitis.In the absence of any diagnostic biochemical testing or tumor markers,imaging modality serves as the key initial impression tool,which can be histologically confirmed only post-resection.While surgery is the only curative option,the use of adjunctive chemotherapy has been considered on top of excision in recent years,with some success.CONCLUSION While this study has taken steps to bridge the gap in the literature,more cases should be reported to further ascertain the current associations and management potential for gallbladder carcinosarcoma.展开更多
BACKGROUND There are concerns that tamoxifen is less effective in Asian women because of the high prevalence of impaired function cytochrome P4502D6(CYP2D6)polymorphisms.AIM To evaluate how knowledge of CYP2D6 genotyp...BACKGROUND There are concerns that tamoxifen is less effective in Asian women because of the high prevalence of impaired function cytochrome P4502D6(CYP2D6)polymorphisms.AIM To evaluate how knowledge of CYP2D6 genotype impacted the choice of hormonal agent and how CYP2D6 genotype and agent were associated with clinical outcomes.METHODS Eighty-two women were recruited.Seventy-eight completed CYP2D6 genotyping and were categorized into poor,intermediate(IM)and extensive or ultra metabolizer phenotypes.Women with poor metabolizer and IM phenotypes were recommended aromatase inhibitors as the preferred agent.RESULTS More than 70%of the women had an IM phenotype,32%an extensive or ultra metabolizer phenotype,and 0%had a poor metabolizer phenotype.Regardless of genotype,more women opted for aromatase inhibitors.Overall,80%of women completed 5 years of hormonal therapy.Five women developed recurrence,3 contralateral breast cancer,5 died,and 1 was diagnosed with a second primary cancer.Five-year recurrence-free and overall survival were slightly better in women with the extensive or ultra metabolizer phenotype compared to those with the IM phenotype,though not statistically significant[P=0.743,hazard ratio(HR):1.441,95%confidence interval(CI):0.191 to 10.17 and P=0.798,HR:1.327,95%CI:0.172 to 9.915,respectively].Women receiving aromatase inhibitors also appeared to have a better,but also nonsignificant,5-year recurrence-free and overall survival(P=0.253,HR:0.368,95%CI:0.031 to 0.258 and P=0.292,HR:0.252,95%CI:0.005 to 4.951,respectively).CONCLUSION The IM phenotype was highly prevalent but was not associated with clinical outcome.展开更多
文摘Corneal neuromas,also termed microneuromas,refer to microscopic,irregula rly-shaped enlargements of terminal subbasal nerve endings at sites of nerve damage or injury.The formation of corneal neuromas results from damage to corneal nerves,such as following corneal pathology or corneal or intraocular surge ries.Initially,denervated areas of sensory nerve fibers become invaded by sprouts of intact sensory nerve fibers,and later injured axons regenerate and new sprouts called neuromas develop.In recent years,analysis of corneal nerve abnormalities including corneal neuromas which can be identified using in vivo confocal microscopy,a non-invasive imaging technique with microscopic resolution,has been used to evaluate corneal neuropathy and ocular surface dysfunction.Corneal neuromas have been shown to be associated with clinical symptoms of discomfort and dryness of eyes,and are a promising surrogate biomarker for ocular surface diseases,such as neuropathic corneal pain,dry eye disease,diabetic corneal neuropathy,neurotrophic keratopathy,Sjogren's syndrome,bullous keratopathy,post-refra ctive surgery,and others.In this review,we have summarized the current literature on the association between these ocular surface diseases and the presentation of corneal microneuromas,as well as elaborated on their pathogenesis,visualization via in vivo confocal microscopy,and utility in monitoring treatment efficacy.As current quantitative analysis on neuromas mainly relies on manual annotation and quantification,which is user-dependent and labor-intensive,future direction includes the development of artificial intelligence software to identify and quantify these potential imaging biomarkers in a more automated and sensitive manner,allowing it to be applied in clinical settings more efficiently.Combining imaging and molecular biomarkers may also help elucidate the associations between corneal neuromas and ocular surface diseases.
基金supported by a Presidential Postdoctoral Fellowship (021229-00001) from Nanyang Technological University,Singapore (to JZ)a Lee Kong Chian School of Medicine Dean’s Postdoctoral Fellowship (021207-00001) from NTU Singaporea Mistletoe Research Fellowship (022522-00001) from the Momental Foundaton,USA (to CHL)
文摘The interaction between metabolic dysfunction and inflammation is central to the development of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease.Obesity-related conditions like type 2 diabetes and non-alcoholic fatty liver disease exacerbate this relationship.Peripheral lipid accumulation,particularly in the liver,initiates a cascade of inflammatory processes that extend to the brain,influencing critical metabolic regulatory regions.Ceramide and palmitate,key lipid components,along with lipid transporters lipocalin-2 and apolipoprotein E,contribute to neuroinflammation by disrupting blood–brain barrier integrity and promoting gliosis.Peripheral insulin resistance further exacerbates brain insulin resistance and neuroinflammation.Preclinical interventions targeting peripheral lipid metabolism and insulin signaling pathways have shown promise in reducing neuroinflammation in animal models.However,translating these findings to clinical practice requires further investigation into human subjects.In conclusion,metabolic dysfunction,peripheral inflammation,and insulin resistance are integral to neuroinflammation and neurodegeneration.Understanding these complex mechanisms holds potential for identifying novel therapeutic targets and improving outcomes for neurodegenerative diseases.
基金supported by National Research Foundation of Korea(NRF)grants funded by the Korean Government(MSIT)[grant numbers RS-2023-00207763 and NRF-2022R1A2C2010350].
文摘Magnesium(Mg)and its alloys have recently gained increasing attention in the biomedical field as promising biodegradable materials with harmless degradation products.Magnesium-based alloys have a wide range of biomedical applications because of their outstanding biocompatibility and unique mechanical properties.Widespread use of Mg-based biomedical devices eliminates the need for post-healing biomaterial removal surgery and minimizes the negative consequences of the implantation of permanent biomaterials,including stress shielding and undesired metal ion release in the body.This paper provides a literature review on the properties and manufacturing methods of Mgbased alloys for biomedical applications,including orthopedic implants,cardiovascular applications,surgical wires and staplers,and antitumor activities.Each application of Mg-based biomaterials is investigated from a biological perspective,including matching functional properties,biocompatibility,host tissue responses,and anti-microbial strategies,along with potential additive manufacturing technologies for these applications.Finally,an outlook is presented to provide recommendations for Mg-based biomaterials in the future.
文摘BACKGROUND Research on long-term survival after resection of giant(≥10 cm)and non-giant hepatocellular carcinoma(HCC)(<10 cm)has produced conflicting results.AIM This study aimed to investigate whether oncological outcomes and safety profiles of resection differ between giant and non-giant HCC.METHODS PubMed,MEDLINE,EMBASE,and Cochrane databases were searched.Studies designed to investigate the outcomes of giant vs non-giant HCC were included.The primary endpoints were overall survival(OS)and disease-free survival(DFS).The secondary endpoints were postoperative complications and mortality rates.All studies were assessed for bias using the Newcastle–Ottawa Scale.RESULTS 24 retrospective cohort studies involving 23747 patients(giant=3326;non-giant=20421)who underwent HCC resection were included.OS was reported in 24 studies,DFS in 17 studies,30-d mortality rate in 18 studies,postoperative complications in 15 studies,and post-hepatectomy liver failure(PHLF)in six studies.The HR was significantly lower for non-giant HCC in both OS(HR 0.53,95%CI:0.50-0.55,P<0.001)and DFS(HR 0.62,95%CI:0.58-0.84,P<0.001).No significant difference was found for 30-d mortality rate(OR 0.73,95%CI:0.50-1.08,P=0.116),postoperative complications(OR 0.81,95%CI:0.62-1.06,P=0.140),and PHLF(OR 0.81,95%CI:0.62-1.06,P=0.140).CONCLUSION Resection of giant HCC is associated with poorer long-term outcomes.The safety profile of resection was similar in both groups;however,this may have been confounded by reporting bias.HCC staging systems should account for the size differences.
文摘BACKGROUND Acute pancreatitis(AP)is a disease spectrum ranging from mild to severe disease.During the coronavirus disease 2019(COVID-19)pandemic,numerous reports of AP have been published,with most authors concluding a causal relationship between COVID-19 and AP.Retrospective case reports or small case series are unable to accurately determine the cause-effect relationship between COVID-19 and AP.AIM To establish whether COVID-19 is a cause of AP using the modified Naranjo scoring system.METHODS A systematic review was conducted on PubMed,World of Science and Embase for articles reporting COVID-19 and AP from inception to August 2021.Exclusion criteria were cases of AP which were not reported to be due to COVID-19 infection,age<18 years old,review articles and retrospective cohort studies.The original 10-item Naranjo scoring system(total score 13)was devised to approximate the likelihood of a clinical presentation to be secondary to an adverse drug reaction.We modified the original scoring system into a 8-item modified Naranjo scoring system(total score 9)to determine the cause-effect relationship between COVID-19 and AP.A cumulative score was decided for each case presented in the included articles.Interpretation of the modified Naranjo scoring system is as follows:≤3:Doubtful,4-6:Possible,≥7:Probable cause.RESULTS The initial search resulted in 909 articles,with 740 articles after removal of duplicates.A total of 67 articles were included in the final analysis,with 76 patients which had AP reported to be due to COVID-19.The mean age was 47.8(range 18-94)years.Majority of patients(73.3%)had≤7 d between onset of COVID-19 infection and diagnosis of AP.There were only 45(59.2%)patients who had adequate investigations to rule out common aetiologies(gallstones,choledocholithiasis,alcohol,hypertriglyceridemia,hypercalcemia and trauma)of AP.Immunoglobulin G4 testing was conducted in 9(13.5%)patients to rule out autoimmune AP.Only 5(6.6%)patients underwent endoscopic ultrasound and/or magnetic resonance cholangiopancreatogram to rule out occult microlithiasis,pancreatic malignancy and pancreas divisum.None of the patients had other recently diagnosed viral infections apart from COVID-19 infection,or underwent genetic testing to rule out hereditary AP.There were 32(42.1%),39(51.3%)and 5(6.6%)patients with doubtful,possible,and probable cause-effect relationship respectively between COVID-19 and AP.CONCLUSION Current evidence is weak to establish a strong link between COVID-19 and AP.Investigations should be performed to rule out other causes of AP before establishing COVID-19 as an aetiology.
文摘BACKGROUND Gastric cancer is one of the leading causes of cancer burden and mortality,often resulting in peritoneal metastasis in advanced stages with negative survival outcomes.Staging laparoscopy has become standard practice for suspected cases before a definitive gastrectomy or palliation.This systematic review aims to compare the efficacy of other diagnostic modalities instead of staging laparoscopy as the alternatives are able to reduce cost and invasive staging procedures.Recently,a radiomic model based on computed tomography and positron emission tomography(PET)has also emerged as another method to predict peritoneal metastasis.AIM To determine if the efficacy of computed tomography,magnetic resonance imaging and PET is comparable with staging laparoscopy.METHODS Articles comparing computed tomography,PET,magnetic resonance imaging,and radiomic models based on computed tomography and PET to staging laparoscopies were filtered out from the Cochrane Library,EMBASE,PubMed,Web of Science,and Reference Citations Analysis(https://www.referencecitationanalysis.com/).In the search for studies comparing computed tomography(CT)to staging laparoscopy,five retrospective studies and three prospective studies were found.Similarly,five retrospective studies and two prospective studies were also included for papers comparing CT to PET scans.Only one retrospective study and one prospective study were found to be suitable for papers comparing CT to magnetic resonance imaging scans.RESULTS Staging laparoscopy outperformed computed tomography in all measured aspects,namely sensitivity,specificity,positive predictive value and negative predictive value.Magnetic resonance imaging and PET produced mixed results,with the former shown to be only marginally better than computed tomography.CT performed slightly better than PET in most measured domains,except in specificity and true negative rates.We speculate that this may be due to the limited F-fluorodeoxyglucose uptake in small peritoneal metastases and in linitis plastica.Radiomic modelling,in its current state,shows promise as an alternative for predicting peritoneal metastases.With further research,deep learning and radiomic modelling can be refined and potentially applied as a preoperative diagnostic tool to reduce the need for invasive staging laparoscopy.CONCLUSION Staging laparoscopy was superior in all measured aspects.However,associated risks and costs must be considered.Refinements in radiomic modelling are necessary to establish it as a reliable screening technique.
文摘performed independently by authors(Yap KY,Chi H,Ng S)identified 50 studies for full-text evaluation.Finally,12 prospective RCTs and 4 non-randomised studies(1 non-randomised trial and 3 observational studies)were included.A detailed PRISMA diagram is shown in Figure 1.The studies included were assessed for risk of bias,with a summary of the assessment shown in Figure 2 and Table 1 for trials and non-interventional studies,respectively.The PRISMA checklist is appended in Supplementary Figure 1.
基金supported by a Lee Kong Chian School of Medicine Dean’s Postdoctoral Fellowship(021207-00001)from Nanyang Technological University Singaporea Mistletoe Research Fellowship(022522-00001)from the Momental Foundation USA(to CHL).
文摘Neuronal necroptosis-an emerging form of regulated cell death associated with neuroinflammatory signaling:Alzheimer’s disease(AD)is characterized by the presence of extracellular amyloid-β(Aβ)plaques and intracellular tau neurofibrillary tangles as well as progressive neuronal loss.Recent evidence has suggested that prolonged neuroinflammation with increased levels of cytokines,arising from neuronal injury,innate immune responses from glial cells,and peripheral inflammation,leads to neuronal death and AD progression.
文摘A pancreatic pseudocyst is defined as an encapsulated fluid collection with a welldefined inflammatory wall with minimal or no necrosis.The diagnosis cannot be made prior to 4 wk after the onset of pancreatitis.The clinical presentation is often nonspecific,with abdominal pain being the most common symptom.If a diagnosis is suspected,contrast-enhanced computed tomography and/or magnetic resonance imaging are performed to confirm the diagnosis and assess the characteristics of the pseudocyst.Endoscopic ultrasound with cyst fluid analysis can be performed in cases of diagnostic uncertainty.Pseudocyst of the pancreas can lead to complications such as hemorrhage,infection,and rupture.The management of pancreatic pseudocysts depends on the presence of symptoms and the development of complications,such as biliary or gastric outlet obstruction.Management options include endoscopic or surgical drainage.The aim of this review was to summarize the current literature on pancreatic pseudocysts and discuss the evolution of the definitions,diagnosis,and management of this condition.
文摘Randomized controlled trials(RCTs)have long been recognized as the gold standard for establishing causal relationships in clinical research.Despite that,various limitations of RCTs prevent its widespread implementation,ranging from the ethicality of withholding potentially-lifesaving treatment from a group to relatively poor external validity due to stringent inclusion criteria,amongst others.However,with the introduction of propensity score matching(PSM)as a retrospective statistical tool,new frontiers in establishing causation in clinical research were opened up.PSM predicts treatment effects using observational data from existing sources such as registries or electronic health records,to create a matched sample of participants who received or did not receive the intervention based on their propensity scores,which takes into account characteristics such as age,gender and comorbidities.Given its retrospective nature and its use of observational data from existing sources,PSM circumvents the aforementioned ethical issues faced by RCTs.Majority of RCTs exclude elderly,pregnant women and young children;thus,evidence of therapy efficacy is rarely proven by robust clinical research for this population.On the other hand,by matching study patient characteristics to that of the population of interest,including the elderly,pregnant women and young children,PSM allows for generalization of results to the wider population and hence greatly increases the external validity.Instead of replacing RCTs with PSM,the synergistic integration of PSM into RCTs stands to provide better research outcomes with both methods complementing each other.For example,in an RCT investigating the impact of mannitol on outcomes among participants of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial,the baseline characteristics of comorbidities and current medications between treatment and control arms were significantly different despite the randomization protocol.Therefore,PSM was incorporated in its analysis to create samples from the treatment and control arms that were matched in terms of these baseline characteristics,thus providing a fairer comparison for the impact of mannitol.This literature review reports the applications,advantages,and considerations of using PSM with RCTs,illustrating its utility in refining randomization,improving external validity,and accounting for non-compliance to protocol.Future research should consider integrating the use of PSM in RCTs to better generalize outcomes to target populations for clinical practice and thereby benefit a wider range of patients,while maintaining the robustness of randomization offered by RCTs.
文摘Liver transplantation represents a pivotal intervention in the management of end-stage liver disease,offering a lifeline to countless patients.Despite significant strides in surgical techniques and organ procurement,ethical dilemmas and de-bates continue to underscore this life-saving procedure.Navigating the ethical terrain surrounding this complex procedure is hence paramount.Dissecting the nuances of ethical principles of justice,autonomy and beneficence that underpin transplant protocols worldwide,we explore the modern challenges that plaques the world of liver transplantation.We investigate the ethical dimensions of organ transplantation,focusing on allocation,emerging technologies,and decision-making processes.PubMed,Scopus,Web of Science,Embase and Central were searched from database inception to February 29,2024 using the following key-words:“liver transplant”,“transplantation”,“liver donation”,“liver recipient”,“organ donation”and“ethics”.Information from relevant articles surrounding ethical discussions in the realm of liver transplantation,especially with regards to organ recipients and allocation,organ donation,transplant tourism,new age technologies and developments,were extracted.From the definition of death to the long term follow up of organ recipients,liver transplantation has many ethical quandaries.With new transplant techniques,societal acceptance and perceptions also play a pivotal role.Cultural,religious and regional factors including but not limited to beliefs,wealth and accessibility are extremely influential in public at-titudes towards donation,xenotransplantation,stem cell research,and adopting artificial intelligence.Understanding and addressing these perspectives whilst upholding bioethical principles is essential to ensure just distribution and fair allocation of resources.Robust regulatory oversight for ethical sourcing of organs,ensuring good patient selection and transplant techniques,and high-quality long-term surveillance to mitigate risks is essential.Efforts to promote equitable access to transplantation as well as prioritizing patients with true needs are essential to address disparities.In conclusion,liver transplantation is often the beacon of hope for individuals suffering from end-stage liver disease and improves quality of life.The ethics related to transplantation are complex and multifaceted,considering not just the donor and the recipient,but also the society as a whole.
基金supported by the Singapore National Research Foundation under its NMRC-CBRG grants(Project award number:NMRC/CBRG/0096/2015) and administered by the Singapore Ministry of Health’s National Medical Research Councilpartially supported by the MOE Academic Research Funding(AcRF) Tier 1 grant(RG148/14) and Tier 2 grant(MOE2015-T2-1-023)
文摘MiR-219 and miR-338(miR-219/miR-338)are oligodendrocyte-specific microRNAs.The overexpression of these miRs in oligodendrocyte precursor cells promotes their differentiation and maturation into oligodendrocytes,which may enhance axonal remyelination after nerve injuries in the central nervous system(CNS).As such,the delivery of miR-219/miR-338 to the CNS to promote oligodendrocyte precursor cell differentiation,maturation and myelination could be a promising approach for nerve repair.However,nerve injuries in the CNS also involve other cell types,such as microglia and astrocytes.Herein,we investigated the effects of miR-219/miR-338 treatment on microglia and astrocytes in vitro and in vivo.We found that miR-219/miR-338 diminished microglial expression of pro-inflammatory cytokines and suppressed astrocyte activation.In addition,we showed that miR-219/miR-338 enhanced oligodendrocyte precursor cell differentiation and maturation in a scratch assay paradigm that re-created a nerve injury condition in vitro.Collectively,our results suggest miR-219/miR-338 as a promising treatment for axonal remyelination in the CNS following nerve injuries.All experimental procedures were approved by the Institutional Animal Care and Use Committee(IACUC),Nanyang Technological University(approval No.A0309 and A0333)on April 27,2016 and October 8,2016.
文摘BACKGROUND Presence of microvascular invasion(MVI)indicates poorer prognosis postcurative resection of hepatocellular carcinoma(HCC),with an increased chance of tumour recurrence.By present standards,MVI can only be diagnosed postoperatively on histopathology.Texture analysis potentially allows identification of patients who are considered‘high risk’through analysis of pre-operative magnetic resonance imaging(MRI)studies.This will allow for better patient selection,improved individualised therapy(such as extended surgical margins or adjuvant therapy)and pre-operative prognostication.AIM This study aims to evaluate the accuracy of texture analysis on pre-operative MRI in predicting MVI in HCC.METHODS Retrospective review of patients with new cases of HCC who underwent hepatectomy between 2007 and 2015 was performed.Exclusion criteria:No preoperative MRI,significant movement artefacts,loss-to-follow-up,ruptured HCCs,previous hepatectomy and adjuvant therapy.Fifty patients were divided into MVI(n=15)and non-MVI(n=35)groups based on tumour histology.Selected images of the tumour on post-contrast-enhanced T1-weighted MRI were analysed.Both qualitative(performed by radiologists)and quantitative data(performed by software)were obtained.Radiomics texture parameters were extracted based on the largest cross-sectional area of each tumor and analysed using MaZda software.Five separate methods were performed.Methods 1,2 and 3 exclusively made use of features derived from arterial,portovenous and equilibrium phases respectively.Methods 4 and 5 made use of the comparatively significant features to attain optimal performance.RESULTS Method 5 achieved the highest accuracy of 87.8%with sensitivity of 73%and specificity of 94%.CONCLUSION Texture analysis of tumours on pre-operative MRI can predict presence of MVI in HCC with accuracies of up to 87.8%and can potentially impact clinical management.
文摘Acute pancreatitis(AP)is a disease spectrum ranging from mild to severe with an unpredictable natural course.Majority of cases(80%)are mild and self-limiting.However,severe AP(SAP)has a mortality risk of up to 30%.Establishing aetiology and risk stratification are essential pillars of clinical care.Idiopathic AP is a diagnosis of exclusion which should only be used after extended investigations fail to identify a cause.Tenets of management of mild AP include pain control and management of aetiology to prevent recurrence.In SAP,patients should be resuscitated with goal-directed fluid therapy using crystalloids and admitted to critical care unit.Routine prophylactic antibiotics have limited clinical benefit and should not be given in SAP.Patients able to tolerate oral intake should be given early enteral nutrition rather than nil by mouth or parenteral nutrition.If unable to tolerate per-orally,nasogastric feeding may be attempted and routine post-pyloric feeding has limited evidence of clinical benefit.Endoscopic retrograde cholangiopancreatogram should be selectively performed in patients with biliary obstruction or suspicion of acute cholangitis.Delayed step-up strategy including percutaneous retroperitoneal drainage,endoscopic debridement,or minimal-access necrosectomy are sufficient in most SAP patients.Patients should be monitored for diabetes mellitus and pseudocyst.
文摘Flaviviruses are positive-sense RNA viruses, and many are important human pathogens. Nonstructural protein 2B and 3 of the flaviviruses(NS2BNS3) form an endoplasmic reticulum(ER) membrane-associated hetero-dimeric complex through the NS2B transmembrane region. The NS2BNS3 complex is multifunctional. The N-terminal region of NS3, and its cofactor NS2B fold into a protease that is responsible for viral polyprotein processing, and the C-terminal domain of NS3 possesses NTPase/RNA helicase activities and is involved in viral RNA replication and virus particle formation. In addition, NS2BNS3 complex has also been shown to modulate viral pathogenesis and the host immune response. Because of the essential functions that the NS2BNS3 complex plays in the flavivirus life cycle, it is an attractive target for antiviral development. This review focuses on the recent biochemical and structural advances of NS2BNS3 and provides a brief update on the current status of drug development targeting this viral protein complex.
文摘The interplay between glucose metabolism and that of the two other primary nutrient classes, amino acids and fatty acids is critical for regulated insulin secretion. Mitochondrial metabolism of glucose, amino acid and fatty acids generates metabolic coupling factors(such as ATP, NADPH, glutamate, long chain acyl-CoA and diacylglycerol) which trigger insulin secretion. The observation of protein induced hypoglycaemia in patients with mutations in GLUD1 gene, encoding the enzyme glutamate dehydrogenase(GDH) and HADH gene, encoding for the enzyme short-chain 3-hydroxyacyl-CoA dehydrogenase has provided new mechanistic insights into the regulation of insulin secretion by amino acid and fatty acid metabolism. Metabolic signals arising from amino acid and fatty acid metabolism converge on the enzyme GDH which integrates both signals from both pathways and controls insulin secretion. Hence GDH seems to play a pivotal role in regulating both amino acid and fatty acid metabolism.
文摘Phosphate is an essential electrolyte for proper mineralisation of bone,buffering of urine,and diverse cellular actions.Hypophosphatemia(HP)is a clinical spectrum which range from asymptomatic to severe complications such as neuromuscular and pulmonary complications,or even death.Post-hepatectomy HP(PHH)has been reported to be 55.5%-100%.Post-hepatectomy,there is rapid uptake of phosphate and increased mitotic counts to aid in regeneration of residual liver.Concurrently,PHH may be due to increased urinary phosphorous from activation of matrix extracellular phosphoglycoprotein in the injured liver,which decreases phosphate influx into hepatocytes to sustain adenosine triphosphate synthesis.A literature review was performed on Pub Med till January 2022.We included 8 studies which reported on impact of PHH on post-operative outcomes.In patients with diseased liver,PHH was reported to have either beneficial or deleterious effects on post-hepatectomy liver failure(PHLF),morbidity and/or mortality in various cohorts.In living donor hepatectomy,PHLF was higher in PHH.Benefits of correction of PHH with reduced postoperative complications have been shown.Correction of PHH should be done based on extent of PHH.Existing studies were however heterogenous;further studies should be conducted to assess PHH on post-operative outcomes with standardized phosphate replacement regimes.
文摘Objective To study the effect of changing heart rate on the ocular pulse and optic nerve head deformations with a viscoelastic lamina cribrosa.Methods An FE model of a healthy eye was reconstructed.The choroid was biphasic and consisted of a solid phase(connective tissues)and a fluid phase(blood).The LC was viscoelastic as characterized by a stress-relaxation test.We applied arterial pressures at 18 entry sites(posterior ciliary arteries)and venous pressures at 4 exit sites(vortex veins).The heart rate was varied from 60 bpm to 120 bpm(increment:20 bpm).We reported the ocular pulse amplitude(OPA),pulse volume,optic nerve head(ONH)deformations and the dynamic modulus of the LC at different heart rates.Results With an increasing heart rate,the OPA decreased by 0.04 mmHg for every 10 bpm increase.The pulse volume also exhibited a linear relationship with heart rate,and decreased by 0.13 L.In addition,the storage modulus and the loss modulus of the LC center increased by 0.014 MPa and 0.04 MPa,respectively for every 10 pm increase in heart rate.Conclusions Our model predicted that the OPA,the pulse volume the ONH deformation decreased at a faster heartrate.We also found that the viscoelastic LC became stiffer with an increasing heart rate.Further studies are required to explore the potential links with the vascular dysregulation and axonal loss in glaucoma.
文摘BACKGROUND Gallbladder carcinosarcoma is a rare hepatobiliary tumor comprising of both carcinomatous and sarcomatous components.Due to its rarity,the literature with regards to the topic is scarce and currently lacking,spanning less than 100 cases.AIM To summarize the current literature on gallbladder carcinosarcoma.METHODS A literature review was performed on the PubMed database using the keywords“Gallbladder”AND“Carcinosarcoma”from 1970 to 2021.Additionally,similar searches were performed on MEDLINE and Web of Science.RESULTS Risk factors noted include female gender,gallstones and chronic cholecystitis.In the absence of any diagnostic biochemical testing or tumor markers,imaging modality serves as the key initial impression tool,which can be histologically confirmed only post-resection.While surgery is the only curative option,the use of adjunctive chemotherapy has been considered on top of excision in recent years,with some success.CONCLUSION While this study has taken steps to bridge the gap in the literature,more cases should be reported to further ascertain the current associations and management potential for gallbladder carcinosarcoma.
基金Supported by the NHG-KTPH Small Innovative Grants(SIG),No.SIG/11009 and No.SIG/15025.
文摘BACKGROUND There are concerns that tamoxifen is less effective in Asian women because of the high prevalence of impaired function cytochrome P4502D6(CYP2D6)polymorphisms.AIM To evaluate how knowledge of CYP2D6 genotype impacted the choice of hormonal agent and how CYP2D6 genotype and agent were associated with clinical outcomes.METHODS Eighty-two women were recruited.Seventy-eight completed CYP2D6 genotyping and were categorized into poor,intermediate(IM)and extensive or ultra metabolizer phenotypes.Women with poor metabolizer and IM phenotypes were recommended aromatase inhibitors as the preferred agent.RESULTS More than 70%of the women had an IM phenotype,32%an extensive or ultra metabolizer phenotype,and 0%had a poor metabolizer phenotype.Regardless of genotype,more women opted for aromatase inhibitors.Overall,80%of women completed 5 years of hormonal therapy.Five women developed recurrence,3 contralateral breast cancer,5 died,and 1 was diagnosed with a second primary cancer.Five-year recurrence-free and overall survival were slightly better in women with the extensive or ultra metabolizer phenotype compared to those with the IM phenotype,though not statistically significant[P=0.743,hazard ratio(HR):1.441,95%confidence interval(CI):0.191 to 10.17 and P=0.798,HR:1.327,95%CI:0.172 to 9.915,respectively].Women receiving aromatase inhibitors also appeared to have a better,but also nonsignificant,5-year recurrence-free and overall survival(P=0.253,HR:0.368,95%CI:0.031 to 0.258 and P=0.292,HR:0.252,95%CI:0.005 to 4.951,respectively).CONCLUSION The IM phenotype was highly prevalent but was not associated with clinical outcome.
