Hepatitis C virus(HCV) infection is a systemic disease that is implicated in multiple extrahepatic organ dysfunction contributing to its protean manifestations. HCV is associated with diverse extrahepatic disorders in...Hepatitis C virus(HCV) infection is a systemic disease that is implicated in multiple extrahepatic organ dysfunction contributing to its protean manifestations. HCV is associated with diverse extrahepatic disorders including atherosclerosis, glucose and lipid metabolic disturbances, alterations in the iron metabolic pathways, and lymphoproliferative diseases over and above the traditional liver manifestations of cirrhosis and hepatocellular carcinoma. The orchestration between HCV major proteins and the liver-muscle-adipose axis, poses a major burden on the global health of human body organs, if not adequately addressed. The close and inseparable associations between chronic HCV infection, metabolic disease, and cardiovascular disorders are specifically important considering the increasing prevalence of obesity and metabolic syndrome, and their economic burden to patients, the healthcare systems, and society. Cellular and molecular mechanisms governing the interplay of these organs and tissues in health and disease are therefore of significant interest. The coexistence of metabolic disorders and chronic hepatitis C infection also enhances the progression to liver fibrosis and hepatocellular carcinoma. The presence of metabolic disorders is believed to influence the chronicity and virulence of HCV leading to liver disease progression. This comprehensive review highlights current knowledge on the metabolic manifestations of hepatitis C and the potential pathways in which these metabolic changes can influence the natural history of the disease.展开更多
Formation of coronary artery pseudoaneurysm after percutaneous coronary intervention is rarely reported. A close review of available literature indicates a trend of growing incidence in recent times. Here, we present ...Formation of coronary artery pseudoaneurysm after percutaneous coronary intervention is rarely reported. A close review of available literature indicates a trend of growing incidence in recent times. Here, we present a case of coronary pseudoaneurysm developing in the left circumflex artery within 50 days of sirolimus-eluting stent implantation in a 47-year-old man who was treated for triple-vessel coronary artery disease. Initially, the patient refused any further treatment. However, considering the rapid growth of pseudoaneurysm and increased severity of symptoms at subsequent follow-up, we decided to treat giant pseudoaneurysm with embolization coils. The procedure was successful and the patient remained asymptomatic thereafter.展开更多
In this case, a young female presented with non-specific features such as fever, sore throat, headache and fatigue. She went on to develop epigastric pain, darkening of urine and jaundice, with no resolution of prior ...In this case, a young female presented with non-specific features such as fever, sore throat, headache and fatigue. She went on to develop epigastric pain, darkening of urine and jaundice, with no resolution of prior symptoms. Physical and Laboratory tests confirmed the primary diagnosis of infectious mononucleosis, however, prior history of treatment with multiple drugs led to a diagnosis of DILI as a complication. Appropriate treatment with I.V. antibiotics, hepatoprotective agents, steroids as well as discontinuation of all potential hepatotoxic agents showed significant improvement in patients’ symptoms and overall condition.展开更多
Background: Vogt-Koyanagi-Harada (VKH) disease is a rare, multisystem autoimmune disorder characterized by bilateral granulomatous panuveitis, with or without extraocular manifestations. Although its exact etiology an...Background: Vogt-Koyanagi-Harada (VKH) disease is a rare, multisystem autoimmune disorder characterized by bilateral granulomatous panuveitis, with or without extraocular manifestations. Although its exact etiology and pathogenesis remain unclear, it is hypothesized to involve T-cell dysregulation targeting melanocyte-containing tissues, including the CNS, eye, ear, and skin. VKH predominantly affects pigmented groups, such as Asians, Hispanics, Indians, Native Americans, and Mediterranean ethnicities, accounting for 7-22.4% of uveitis cases. Retrospective analyses indicate a higher incidence among female patients, with most cases occurring in the second and fifth decades of life. Aim: This case report discusses a patient with probable VKH who exhibited ocular, neurologic, and auditory symptoms typical of the prodromal or acute uveitic phase and responded well to prompt management. Case Presentation: A young female in her late 20s presented with low-grade fever, severe headache, neck pain, and neck stiffness. She had received symptomatic treatment at another hospital without relief. She was empirically started on intravenous antibiotics and dexamethasone for suspected pyogenic meningitis and was discharged upon symptom relief. However, she returned two days later due to symptom recurrence. Ophthalmic examination revealed decreased visual acuity bilaterally (6/24), sluggish pupil reaction, optic disc edema, and bilateral macular serous detachments. Mild vitritis with anterior chamber cells and iris pigment on the anterior lens capsule was noted in the left eye. Systemic examination was unremarkable, except for fine crepitations in the bilateral lower lung fields. Management: Considering VKH disease, the patient was started on intravenous methylprednisolone pulse therapy (1 gram/day) for 3 days, followed by oral steroids and topical steroid drops for the eyes. She was discharged with oral prednisolone and prednisolone acetate 1% eye drops. At follow-up, her vision improved, and there was resolution of papillitis and serous retinal detachments. Conclusions: VKH is a significant cause of bilateral vision loss. This case of probable VKH syndrome underscores the importance of early recognition and aggressive treatment in achieving a favorable visual prognosis.展开更多
Objective: The aim was to show that Minimally Invasive total arterial revascularization for left main stem coronary artery disease, via a left anterior Mini thoracotomy using bilateral internal thoracic arteries is fe...Objective: The aim was to show that Minimally Invasive total arterial revascularization for left main stem coronary artery disease, via a left anterior Mini thoracotomy using bilateral internal thoracic arteries is feasible, reproducible and safe. Further, there has been no exclusive data or experience with minimally invasive coronary artery bypass grafting in left main stem disease. Methods: From April 2019 to March 2024, 41 patients with left main stem stenosis, left main equivalent disease and unprotected left main with triple vessel disease underwent off pump minimally invasive multivessel coronary artery bypass grafting using either in situ pedicled Bilateral Internal Thoracic arteries or Left and Right Internal Thoracic artery Y composite conduits at three centers. Bilateral Internal Thoracic arteries were harvested under direct vision. All patients had an Intra-Aortic Balloon Pump inserted via the femoral artery prior to induction of anesthesia, to prevent any hemodynamic instability, arrhythmias, and was removed following completion of the procedure in the operating room without any complications. Efficacy and outcomes were evaluated by i) Primary (MACCE)-Major Adverse Cardiac and Cardiovascular events and ii) Secondary outcome measures including total length of stay, return to full physical activity and quality of life. Mean follow-up was 1.4 years (Maximum was 2.5 years). Results: 41 patients with left main stem coronary artery stenosis, underwent total arterial revascularization using bilateral internal thoracic arteries. Left main stem stenosis was present in 29 patients, Unprotected left main stem stenosis with triple vessel disease in 7 and left main equivalence in 5 patients. In this cohort, 29 patients with only left main stem stenosis had 2 grafts each, 7 patients with left main and triple vessel disease had 3 grafts and 5 patients with left main equivalent disease had 2 grafts respectively. The average number of grafts was 2.2. One patient was converted to open sternotomy as an emergency because of hemodynamic instability and myocardial revascularization was done on cardiopulmonary bypass (2.2%). The average hospital stay was 3.7 days. Ejection fraction was 45% ± 5%. There was one mortality (2.2%) but no major morbidity. The average ICU and hospital stay was 24 ± 4 hours and 3.7 days. All patients were free from major adverse cardiac and cerebrovascular events at follow-up. Conclusions: Multivessel total arterial revascularization using left and right internal thoracic arteries, was performed via a left anterior Mini thoracotomy on patients with left main stem disease and showed that it was safe, reproducible and will help extend the armamentarium of the surgeon in minimally invasive Coronary artery bypass grafting. Concomitantly it helped enhance the potential for shorter hospital stay, increased survival, decreased morbidity, and earlier return to full activity. Furthermore, the safety, efficacy, and outcomes of minimally invasive coronary artery bypass grafting in this high-risk group evaluated by primary and secondary outcome measures have been good in this study.展开更多
Non-alcoholic fatty liver disease(NAFLD)is emerging as a common cause of chronic liver disease in children and adults.NAFLD can progress to steatohepa-titis and potentially even hepatocellular carcinoma.Early identifi...Non-alcoholic fatty liver disease(NAFLD)is emerging as a common cause of chronic liver disease in children and adults.NAFLD can progress to steatohepa-titis and potentially even hepatocellular carcinoma.Early identification of pati-ents at risk for progressive disease is crucial for managing NAFLD.Recent studies have identified long noncoding RNAs(lncRNAs),circular RNAs,and microRNAs as playing important roles in the pathogenesis of NAFLD.These noncoding RNAs are involved in modulating several metabolic pathways such as hepatic glucose and lipid metabolism,oxidative stress,and even carcinogenesis.Elevated levels of lncARSR and lncRNA nuclear-enriched abundant transcript 1 have been found in patients with NAFLD.In addition,lncRNAs such as PRYP4-3 and RP11-128N14.5 can distinguish patients with NAFLD from healthy indi-viduals.Increased MEG3 expression has been observed in both NAFLD and non-alcoholic steatohepatitis,suggesting that it may help predict patients at risk for disease progression.With advances in transcriptomics,we may discover additional targets to help in the identification and prognostication of NAFLD.展开更多
BACKGROUND Multitudinous advancements have been made to the traditional microfracture(MFx)technique,which have involved delivery of various acellular 2nd generation MFx and cellular MFx-III components to the area of c...BACKGROUND Multitudinous advancements have been made to the traditional microfracture(MFx)technique,which have involved delivery of various acellular 2nd generation MFx and cellular MFx-III components to the area of cartilage defect.The relative benefits and pitfalls of these diverse modifications of MFx technique are still not widely understood.AIM To comparatively analyze the functional,radiological,and histological outcomes,and complications of various generations of MFx available for the treatment of cartilage defects.METHODS A systematic review was performed using PubMed,EMBASE,Web of Science,Cochrane,and Scopus.Patients of any age and sex with cartilage defects undergoing any form of MFx were considered for analysis.We included only randomized controlled trials(RCTs)reporting functional,radiological,histological outcomes or complications of various generations of MFx for the management of cartilage defects.Network meta-analysis(NMA)was conducted in Stata and Cochrane’s Confidence in NMA approach was utilized for appraisal of evidence.RESULTS Forty-four RCTs were included in the analysis with patients of mean age of 39.40(±9.46)years.Upon comparing the results of the other generations with MFX-I as a constant comparator,we noted a trend towards better pain control and functional outcome(KOOS,IKDC,and Cincinnati scores)at the end of 1-,2-,and 5-year time points with MFx-III,although the differences were not statistically significant(P>0.05).We also noted statistically significant Magnetic resonance observation of cartilage repair tissue score in the higher generations of microfracture(weighted mean difference:17.44,95%confidence interval:0.72,34.16,P=0.025;without significant heterogeneity)at 1 year.However,the difference was not maintained at 2 years.There was a trend towards better defect filling on MRI with the second and third generation MFx,although the difference was not statistically significant(P>0.05).CONCLUSION The higher generations of traditional MFx technique utilizing acellular and cellular components to augment its potential in the management of cartilage defects has shown only marginal improvement in the clinical and radiological outcomes.展开更多
Laubry-Pezzi syndrome(L-PS)is a rare congenital heart disease characterized by a ventricular septal defect(VSD)and aortic valve prolapse.These cardiac lesions predispose individuals to infective endocarditis(IE),a lif...Laubry-Pezzi syndrome(L-PS)is a rare congenital heart disease characterized by a ventricular septal defect(VSD)and aortic valve prolapse.These cardiac lesions predispose individuals to infective endocarditis(IE),a lifethreatening complication,especially in resource-constrained settings.A 17-year-old male presented with a three-week history of fever and headache,and a one-week history of abdominal pain,vomiting,and diarrhea.On presentation,he appeared toxic,was febrile,tachypneic,tachycardic,and blood pressure of 120/30 mmHg,and heart sounds were S1,S2.Abdominal examination revealed generalized tenderness.A provisional diagnosis of typhoid sepsis with intestinal perforation was considered.However,a thorough clinical evaluation led to the definitive diagnosis of L-PS complicated by right-sided IE,sepsis,acute kidney injury,acute heart failure,and haemoptysis.Despite significant improvement with appropriate antibiotics and adjunctive therapy,the patient’s inability to afford surgical correction and subsequent non-adherence to medical advice he resorted to traditional medicine this led to readmission for heart failure.This case highlights the diagnostic and treatment challenges associated with L-PS with life-threatening complications,particularly in resource-constrained settings,where it may be misdiagnosed as common infections like typhoid sepsis with intestinal perforation.It emphasizes the importance of a comprehensive clinical approach,including a detailed history,meticulous physical examination,and targeted investigations,to ensure accurate diagnosis and timely intervention in patients with L-PS and its life-threatening complications.展开更多
Background:Hepatocellular carcinoma(HCC)is one of the deadliest cancer over the world.In this study,we aimed to determine the most critical molecular event in HCC patients with tumor protein p53(TP53)or catenin beta 1...Background:Hepatocellular carcinoma(HCC)is one of the deadliest cancer over the world.In this study,we aimed to determine the most critical molecular event in HCC patients with tumor protein p53(TP53)or catenin beta 1(CTNNB1)mutations,and to explore how these two mutations differ in their impact on HCC prognostication.Methods:We performed an integrated comparative analysis of exome and transcriptome data from The Cancer Genome Atlas(TCGA)for HCC patients.Patient prognosis and correlation with the immune infiltration characteristics were performed.HCC cell line based in vitro experiments were also performed to validate the mechanistic insights.Results:The 3-year progression-free survival(PFS)analysis of HCC patients with TP53 mutations indicated a significantly poorer clinical outcome compared to those with CTNNB1 mutations.Functional annotation of the TP53 mutant cohort revealed a substantial upregulation of genes associated with immune regulation,while the CTNNB1 mutant cohort displayed a prominent activation of metabolic pathways.Further comparative analysis and in vitro experiments showed that TP53 missense mutations activated the signal transducer and activator of transcription 3(STAT3)signaling pathway,which fostered neutrophil infiltration and enhanced the enrichment of regulatory T(Treg)cells by secreting specific inflammatory molecules in the tumor microenvironment.Notably,treatment with a an STAT3 inhibitor suppressed the expression of these inflammatory molecules,underscoring how an immunosuppressive tumor microenvironment in the TP53 mutant cohort contributes to a poor prognosis.Conclusion:Our study provides valuable insights,revealing that HCC patients with TP53 missense mutations exhibit a distinct immune profile associated with poorer clinical outcome compared to those with CTNNB1 mutations.展开更多
文摘Hepatitis C virus(HCV) infection is a systemic disease that is implicated in multiple extrahepatic organ dysfunction contributing to its protean manifestations. HCV is associated with diverse extrahepatic disorders including atherosclerosis, glucose and lipid metabolic disturbances, alterations in the iron metabolic pathways, and lymphoproliferative diseases over and above the traditional liver manifestations of cirrhosis and hepatocellular carcinoma. The orchestration between HCV major proteins and the liver-muscle-adipose axis, poses a major burden on the global health of human body organs, if not adequately addressed. The close and inseparable associations between chronic HCV infection, metabolic disease, and cardiovascular disorders are specifically important considering the increasing prevalence of obesity and metabolic syndrome, and their economic burden to patients, the healthcare systems, and society. Cellular and molecular mechanisms governing the interplay of these organs and tissues in health and disease are therefore of significant interest. The coexistence of metabolic disorders and chronic hepatitis C infection also enhances the progression to liver fibrosis and hepatocellular carcinoma. The presence of metabolic disorders is believed to influence the chronicity and virulence of HCV leading to liver disease progression. This comprehensive review highlights current knowledge on the metabolic manifestations of hepatitis C and the potential pathways in which these metabolic changes can influence the natural history of the disease.
文摘Formation of coronary artery pseudoaneurysm after percutaneous coronary intervention is rarely reported. A close review of available literature indicates a trend of growing incidence in recent times. Here, we present a case of coronary pseudoaneurysm developing in the left circumflex artery within 50 days of sirolimus-eluting stent implantation in a 47-year-old man who was treated for triple-vessel coronary artery disease. Initially, the patient refused any further treatment. However, considering the rapid growth of pseudoaneurysm and increased severity of symptoms at subsequent follow-up, we decided to treat giant pseudoaneurysm with embolization coils. The procedure was successful and the patient remained asymptomatic thereafter.
文摘In this case, a young female presented with non-specific features such as fever, sore throat, headache and fatigue. She went on to develop epigastric pain, darkening of urine and jaundice, with no resolution of prior symptoms. Physical and Laboratory tests confirmed the primary diagnosis of infectious mononucleosis, however, prior history of treatment with multiple drugs led to a diagnosis of DILI as a complication. Appropriate treatment with I.V. antibiotics, hepatoprotective agents, steroids as well as discontinuation of all potential hepatotoxic agents showed significant improvement in patients’ symptoms and overall condition.
文摘Background: Vogt-Koyanagi-Harada (VKH) disease is a rare, multisystem autoimmune disorder characterized by bilateral granulomatous panuveitis, with or without extraocular manifestations. Although its exact etiology and pathogenesis remain unclear, it is hypothesized to involve T-cell dysregulation targeting melanocyte-containing tissues, including the CNS, eye, ear, and skin. VKH predominantly affects pigmented groups, such as Asians, Hispanics, Indians, Native Americans, and Mediterranean ethnicities, accounting for 7-22.4% of uveitis cases. Retrospective analyses indicate a higher incidence among female patients, with most cases occurring in the second and fifth decades of life. Aim: This case report discusses a patient with probable VKH who exhibited ocular, neurologic, and auditory symptoms typical of the prodromal or acute uveitic phase and responded well to prompt management. Case Presentation: A young female in her late 20s presented with low-grade fever, severe headache, neck pain, and neck stiffness. She had received symptomatic treatment at another hospital without relief. She was empirically started on intravenous antibiotics and dexamethasone for suspected pyogenic meningitis and was discharged upon symptom relief. However, she returned two days later due to symptom recurrence. Ophthalmic examination revealed decreased visual acuity bilaterally (6/24), sluggish pupil reaction, optic disc edema, and bilateral macular serous detachments. Mild vitritis with anterior chamber cells and iris pigment on the anterior lens capsule was noted in the left eye. Systemic examination was unremarkable, except for fine crepitations in the bilateral lower lung fields. Management: Considering VKH disease, the patient was started on intravenous methylprednisolone pulse therapy (1 gram/day) for 3 days, followed by oral steroids and topical steroid drops for the eyes. She was discharged with oral prednisolone and prednisolone acetate 1% eye drops. At follow-up, her vision improved, and there was resolution of papillitis and serous retinal detachments. Conclusions: VKH is a significant cause of bilateral vision loss. This case of probable VKH syndrome underscores the importance of early recognition and aggressive treatment in achieving a favorable visual prognosis.
文摘Objective: The aim was to show that Minimally Invasive total arterial revascularization for left main stem coronary artery disease, via a left anterior Mini thoracotomy using bilateral internal thoracic arteries is feasible, reproducible and safe. Further, there has been no exclusive data or experience with minimally invasive coronary artery bypass grafting in left main stem disease. Methods: From April 2019 to March 2024, 41 patients with left main stem stenosis, left main equivalent disease and unprotected left main with triple vessel disease underwent off pump minimally invasive multivessel coronary artery bypass grafting using either in situ pedicled Bilateral Internal Thoracic arteries or Left and Right Internal Thoracic artery Y composite conduits at three centers. Bilateral Internal Thoracic arteries were harvested under direct vision. All patients had an Intra-Aortic Balloon Pump inserted via the femoral artery prior to induction of anesthesia, to prevent any hemodynamic instability, arrhythmias, and was removed following completion of the procedure in the operating room without any complications. Efficacy and outcomes were evaluated by i) Primary (MACCE)-Major Adverse Cardiac and Cardiovascular events and ii) Secondary outcome measures including total length of stay, return to full physical activity and quality of life. Mean follow-up was 1.4 years (Maximum was 2.5 years). Results: 41 patients with left main stem coronary artery stenosis, underwent total arterial revascularization using bilateral internal thoracic arteries. Left main stem stenosis was present in 29 patients, Unprotected left main stem stenosis with triple vessel disease in 7 and left main equivalence in 5 patients. In this cohort, 29 patients with only left main stem stenosis had 2 grafts each, 7 patients with left main and triple vessel disease had 3 grafts and 5 patients with left main equivalent disease had 2 grafts respectively. The average number of grafts was 2.2. One patient was converted to open sternotomy as an emergency because of hemodynamic instability and myocardial revascularization was done on cardiopulmonary bypass (2.2%). The average hospital stay was 3.7 days. Ejection fraction was 45% ± 5%. There was one mortality (2.2%) but no major morbidity. The average ICU and hospital stay was 24 ± 4 hours and 3.7 days. All patients were free from major adverse cardiac and cerebrovascular events at follow-up. Conclusions: Multivessel total arterial revascularization using left and right internal thoracic arteries, was performed via a left anterior Mini thoracotomy on patients with left main stem disease and showed that it was safe, reproducible and will help extend the armamentarium of the surgeon in minimally invasive Coronary artery bypass grafting. Concomitantly it helped enhance the potential for shorter hospital stay, increased survival, decreased morbidity, and earlier return to full activity. Furthermore, the safety, efficacy, and outcomes of minimally invasive coronary artery bypass grafting in this high-risk group evaluated by primary and secondary outcome measures have been good in this study.
文摘Non-alcoholic fatty liver disease(NAFLD)is emerging as a common cause of chronic liver disease in children and adults.NAFLD can progress to steatohepa-titis and potentially even hepatocellular carcinoma.Early identification of pati-ents at risk for progressive disease is crucial for managing NAFLD.Recent studies have identified long noncoding RNAs(lncRNAs),circular RNAs,and microRNAs as playing important roles in the pathogenesis of NAFLD.These noncoding RNAs are involved in modulating several metabolic pathways such as hepatic glucose and lipid metabolism,oxidative stress,and even carcinogenesis.Elevated levels of lncARSR and lncRNA nuclear-enriched abundant transcript 1 have been found in patients with NAFLD.In addition,lncRNAs such as PRYP4-3 and RP11-128N14.5 can distinguish patients with NAFLD from healthy indi-viduals.Increased MEG3 expression has been observed in both NAFLD and non-alcoholic steatohepatitis,suggesting that it may help predict patients at risk for disease progression.With advances in transcriptomics,we may discover additional targets to help in the identification and prognostication of NAFLD.
文摘BACKGROUND Multitudinous advancements have been made to the traditional microfracture(MFx)technique,which have involved delivery of various acellular 2nd generation MFx and cellular MFx-III components to the area of cartilage defect.The relative benefits and pitfalls of these diverse modifications of MFx technique are still not widely understood.AIM To comparatively analyze the functional,radiological,and histological outcomes,and complications of various generations of MFx available for the treatment of cartilage defects.METHODS A systematic review was performed using PubMed,EMBASE,Web of Science,Cochrane,and Scopus.Patients of any age and sex with cartilage defects undergoing any form of MFx were considered for analysis.We included only randomized controlled trials(RCTs)reporting functional,radiological,histological outcomes or complications of various generations of MFx for the management of cartilage defects.Network meta-analysis(NMA)was conducted in Stata and Cochrane’s Confidence in NMA approach was utilized for appraisal of evidence.RESULTS Forty-four RCTs were included in the analysis with patients of mean age of 39.40(±9.46)years.Upon comparing the results of the other generations with MFX-I as a constant comparator,we noted a trend towards better pain control and functional outcome(KOOS,IKDC,and Cincinnati scores)at the end of 1-,2-,and 5-year time points with MFx-III,although the differences were not statistically significant(P>0.05).We also noted statistically significant Magnetic resonance observation of cartilage repair tissue score in the higher generations of microfracture(weighted mean difference:17.44,95%confidence interval:0.72,34.16,P=0.025;without significant heterogeneity)at 1 year.However,the difference was not maintained at 2 years.There was a trend towards better defect filling on MRI with the second and third generation MFx,although the difference was not statistically significant(P>0.05).CONCLUSION The higher generations of traditional MFx technique utilizing acellular and cellular components to augment its potential in the management of cartilage defects has shown only marginal improvement in the clinical and radiological outcomes.
文摘Laubry-Pezzi syndrome(L-PS)is a rare congenital heart disease characterized by a ventricular septal defect(VSD)and aortic valve prolapse.These cardiac lesions predispose individuals to infective endocarditis(IE),a lifethreatening complication,especially in resource-constrained settings.A 17-year-old male presented with a three-week history of fever and headache,and a one-week history of abdominal pain,vomiting,and diarrhea.On presentation,he appeared toxic,was febrile,tachypneic,tachycardic,and blood pressure of 120/30 mmHg,and heart sounds were S1,S2.Abdominal examination revealed generalized tenderness.A provisional diagnosis of typhoid sepsis with intestinal perforation was considered.However,a thorough clinical evaluation led to the definitive diagnosis of L-PS complicated by right-sided IE,sepsis,acute kidney injury,acute heart failure,and haemoptysis.Despite significant improvement with appropriate antibiotics and adjunctive therapy,the patient’s inability to afford surgical correction and subsequent non-adherence to medical advice he resorted to traditional medicine this led to readmission for heart failure.This case highlights the diagnostic and treatment challenges associated with L-PS with life-threatening complications,particularly in resource-constrained settings,where it may be misdiagnosed as common infections like typhoid sepsis with intestinal perforation.It emphasizes the importance of a comprehensive clinical approach,including a detailed history,meticulous physical examination,and targeted investigations,to ensure accurate diagnosis and timely intervention in patients with L-PS and its life-threatening complications.
文摘Background:Hepatocellular carcinoma(HCC)is one of the deadliest cancer over the world.In this study,we aimed to determine the most critical molecular event in HCC patients with tumor protein p53(TP53)or catenin beta 1(CTNNB1)mutations,and to explore how these two mutations differ in their impact on HCC prognostication.Methods:We performed an integrated comparative analysis of exome and transcriptome data from The Cancer Genome Atlas(TCGA)for HCC patients.Patient prognosis and correlation with the immune infiltration characteristics were performed.HCC cell line based in vitro experiments were also performed to validate the mechanistic insights.Results:The 3-year progression-free survival(PFS)analysis of HCC patients with TP53 mutations indicated a significantly poorer clinical outcome compared to those with CTNNB1 mutations.Functional annotation of the TP53 mutant cohort revealed a substantial upregulation of genes associated with immune regulation,while the CTNNB1 mutant cohort displayed a prominent activation of metabolic pathways.Further comparative analysis and in vitro experiments showed that TP53 missense mutations activated the signal transducer and activator of transcription 3(STAT3)signaling pathway,which fostered neutrophil infiltration and enhanced the enrichment of regulatory T(Treg)cells by secreting specific inflammatory molecules in the tumor microenvironment.Notably,treatment with a an STAT3 inhibitor suppressed the expression of these inflammatory molecules,underscoring how an immunosuppressive tumor microenvironment in the TP53 mutant cohort contributes to a poor prognosis.Conclusion:Our study provides valuable insights,revealing that HCC patients with TP53 missense mutations exhibit a distinct immune profile associated with poorer clinical outcome compared to those with CTNNB1 mutations.
